Abstract

Plasmids are and will remain important cloning vehicles for biotechnology. They have also been associated with the spread of a number of diseases and therefore are a subject of environmental concern. With the advent of sequencing technologies, the database of plasmids is increasing. It will be of immense importance to identify the various bacterial hosts in which the plasmid can replicate. The present review article describes the features that confer broad host range to the plasmids, the molecular basis of plasmid host range evolution, and applications in recombinant DNA technology and environment.

Introduction

Plasmids since their discovery have been detected in many different genera. Various microorganisms in which a plasmid can replicate and be maintained is called its host range. Accordingly, plasmids can be classified into narrow and broad host ranges (BHR). The first classification into these two groups was made in 1972 by (Datta & Hedges, 1972), who defined BHR plasmids as those which are able to transfer among Enterobacteria and Pseudomonas spp. However, according to the current understanding, BHR plasmids transfer and maintain among bacteria belonging to different phylogenetic subgroups (Top et al., 1998).

Broad host range plasmids are of considerable interest because they not only play an important role in horizontal gene transfer but also their replicons can serve as good sources for vector construction. Several barriers limit plasmid transfer between unrelated bacteria: interactions at the cell surface may prevent effective mating contact, restriction systems may degrade foreign DNA, or the plasmid may not replicate in the new host. There are several reviews published on BHR plasmids (Kues & Stahl, 1989; del Solar et al., 1993, 1996; Sakai & Komano, 1996). However, in the era of genomics and mobile metagenomics, it would be of immense importance to predict the host range of the plasmid based on the sequence information. For this, it is worth listing the general features that confer broad host range properties to the plasmid. In the present review, we describe the possible reasons behind the unique capability of plasmids to replicate and maintain in varied hosts, molecular basis of host range evolution, and their application in recombinant DNA technology.

Factors affecting broad host range (BHR) plasmid replication

Some well-characterized naturally occurring BHR plasmids and their host range determined so far are shown in Table 1. There are a number of features, which determine the host range of plasmids.

Table 1

Naturally occurring broad host range plasmids described according to their sizes

Plasmid Size (kb) Antibiotic resistance markers Microorganism from which isolated Host range Reference 
pBC1 1.6 Cryptic Bacillus coagulans Zu1961 E. coli, B. subtilis, B. amyloliquefaciens, S.aureus, S. carnosus, and Lactobacillus reuteri De Rossi et al. (1992
pEP2 1.85 Cryptic Corynebacterium diphtheriae Corynebacteria, Mycobacteria, and E. coli Zhang et al. (1994
pWVO1 2.2 Cryptic Lactococcus lactis subsp. cremoris Bacilli, Lactococci, Streptococci, Clostridia and Staphylococci, E. coli Leenhouts et al. (1991
pLF1311 2.38 Cryptic Lactobacillus fermentum VKM1311 E. coli, Lactobacillus, Lactococcus, Enterococcus, Bacillus Aleshin et al. (1999
pAP1 2.4 Cryptic Arcanobacterium (Actinomyces) pyogenes E. coli, Corynebacterium pseudotuberculosis, Arcanobacterium Billington et al. (1998
pBBR1 2.6 Cryptic Bordetella bronchiseptica E. coli, Bordetella pertussis, B. bronchiseptica, Vibrio cholerae, Rhizobium meliloti, Pseudomonas putida Szpirer et al. (2001
pWKS1 2.69 Cryptic Paracoccus pantotrophus DSM 11072 Paracoccus, Agrobacterium tumefaciens, Rhizobium leguminosarum, and Rhodobacter sphaeroides Bartosik et al. (2002
pLS1 4.40 Tc Streptococcus agalactiae Streptococcus pneumoniae, Bacillus subtilis, E. coli Lacks et al. (1986
pUB6060 5.8 Cryptic Plesiomonas shigelloides Aeromonas, Pseudomonas, Stenotrophomonas, Plesiomonas Avison et al. (2001
pJD4 7.4 Ap Neisseria gonorrhoeae N. gonorrhoeae, E. coli, Salmonella enterica serotype Minnesota, Haemophilus influenzae Pagotto & Dillon (2001
RSF1010/R1162/R300B 8.68 Sm, sulfonamides E. coli/P. aeruginosa/Samonella enterica serovar Typhimurium Mycobacterium smegmatis, S. lividans, E.coli, S. cerevisiae, Schizosaccharomyces pombe, Kluyveromyces lactis, Agrobacterium, Cyanobacteria, Pichia angusta (Hansenula polymorpha), and Pachysolen tannophilus Scherzinger et al. (1984) and Meyer et al. (1982
pIJ101 8.9 Cryptic Streptomyces lividans Several Streptomyces spp. Kieser et al. (1982
pSN22 11 Cryptic Streptomyces nigrifaciens Streptomyces, Staphylococci, Actinomadura, etc. Kataoka et al. (1991
pAMβ1 26.5 Em, Lincomycin Streptocococcus faecalis Streptococcus lactis, Lactobacilli, Bacilli, Listeria monocytogenes Clewell et al. (1974
pIP501 30.2 Em, Cm Streptococcus agalactiae Streptococci, Staphylococci, Enterococci, Listeria, Streptomyces lividans, E. coli Horodniceanu et al. (1976
ZM6100(Sa) 39 Km, Sp, Cm Zymomonas mobilis ZM6100(Sa) Z. mobilis, E. coli Strzelecki et al. (1987
pCU1 39 Sp, Sm, Ap Purple bacteria Agrobacterium, Bradyrhizobium, and Rhizobium Krishnan & Iyer (1988
RA3 45.9 Sp, Sm, Cm Aeromonas spp. Alpha-, Beta-, and Gammaproteobacteria Kulinska et al. (2008
pMOL98 55.5 Cryptic Polluted soil captured in C. metallidurans β-proteobacteria (predicted) Van der Auwera et al. (2009
RK2/RP4/RP1/R68 60 Km, Tc, Ap Pseudomonas aeruginosa Many Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Pseudomonas putida, Azotobacter vinelandii, Erwinia crysanthemi, Erwinia amylovora, Erwinia herbicola, Ochrobactrum anthropi Thomas et al. (1982) and Pansegrau et al. (1994
pB10 64.5 Tc, Sm, Amoxicillin and sulfonamides Waste water treatment plant Alpha-, Beta-, and Gammaproteobacteria De Gelder et al. (2005
Plasmid Size (kb) Antibiotic resistance markers Microorganism from which isolated Host range Reference 
pBC1 1.6 Cryptic Bacillus coagulans Zu1961 E. coli, B. subtilis, B. amyloliquefaciens, S.aureus, S. carnosus, and Lactobacillus reuteri De Rossi et al. (1992
pEP2 1.85 Cryptic Corynebacterium diphtheriae Corynebacteria, Mycobacteria, and E. coli Zhang et al. (1994
pWVO1 2.2 Cryptic Lactococcus lactis subsp. cremoris Bacilli, Lactococci, Streptococci, Clostridia and Staphylococci, E. coli Leenhouts et al. (1991
pLF1311 2.38 Cryptic Lactobacillus fermentum VKM1311 E. coli, Lactobacillus, Lactococcus, Enterococcus, Bacillus Aleshin et al. (1999
pAP1 2.4 Cryptic Arcanobacterium (Actinomyces) pyogenes E. coli, Corynebacterium pseudotuberculosis, Arcanobacterium Billington et al. (1998
pBBR1 2.6 Cryptic Bordetella bronchiseptica E. coli, Bordetella pertussis, B. bronchiseptica, Vibrio cholerae, Rhizobium meliloti, Pseudomonas putida Szpirer et al. (2001
pWKS1 2.69 Cryptic Paracoccus pantotrophus DSM 11072 Paracoccus, Agrobacterium tumefaciens, Rhizobium leguminosarum, and Rhodobacter sphaeroides Bartosik et al. (2002
pLS1 4.40 Tc Streptococcus agalactiae Streptococcus pneumoniae, Bacillus subtilis, E. coli Lacks et al. (1986
pUB6060 5.8 Cryptic Plesiomonas shigelloides Aeromonas, Pseudomonas, Stenotrophomonas, Plesiomonas Avison et al. (2001
pJD4 7.4 Ap Neisseria gonorrhoeae N. gonorrhoeae, E. coli, Salmonella enterica serotype Minnesota, Haemophilus influenzae Pagotto & Dillon (2001
RSF1010/R1162/R300B 8.68 Sm, sulfonamides E. coli/P. aeruginosa/Samonella enterica serovar Typhimurium Mycobacterium smegmatis, S. lividans, E.coli, S. cerevisiae, Schizosaccharomyces pombe, Kluyveromyces lactis, Agrobacterium, Cyanobacteria, Pichia angusta (Hansenula polymorpha), and Pachysolen tannophilus Scherzinger et al. (1984) and Meyer et al. (1982
pIJ101 8.9 Cryptic Streptomyces lividans Several Streptomyces spp. Kieser et al. (1982
pSN22 11 Cryptic Streptomyces nigrifaciens Streptomyces, Staphylococci, Actinomadura, etc. Kataoka et al. (1991
pAMβ1 26.5 Em, Lincomycin Streptocococcus faecalis Streptococcus lactis, Lactobacilli, Bacilli, Listeria monocytogenes Clewell et al. (1974
pIP501 30.2 Em, Cm Streptococcus agalactiae Streptococci, Staphylococci, Enterococci, Listeria, Streptomyces lividans, E. coli Horodniceanu et al. (1976
ZM6100(Sa) 39 Km, Sp, Cm Zymomonas mobilis ZM6100(Sa) Z. mobilis, E. coli Strzelecki et al. (1987
pCU1 39 Sp, Sm, Ap Purple bacteria Agrobacterium, Bradyrhizobium, and Rhizobium Krishnan & Iyer (1988
RA3 45.9 Sp, Sm, Cm Aeromonas spp. Alpha-, Beta-, and Gammaproteobacteria Kulinska et al. (2008
pMOL98 55.5 Cryptic Polluted soil captured in C. metallidurans β-proteobacteria (predicted) Van der Auwera et al. (2009
RK2/RP4/RP1/R68 60 Km, Tc, Ap Pseudomonas aeruginosa Many Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Pseudomonas putida, Azotobacter vinelandii, Erwinia crysanthemi, Erwinia amylovora, Erwinia herbicola, Ochrobactrum anthropi Thomas et al. (1982) and Pansegrau et al. (1994
pB10 64.5 Tc, Sm, Amoxicillin and sulfonamides Waste water treatment plant Alpha-, Beta-, and Gammaproteobacteria De Gelder et al. (2005

Experimentally determined and reported host range.

Presence of multiple origins

Some plasmids have multiple origins and one origin functions in one type of host and the others are functional in other hosts. Examples of such plasmids are pJD4 (IncW) and pCU1 (IncN). The BHR plasmid pJD4 (7.4 kb) isolated from Neisseria gonorrhoeae was found to contain three clustered but distinguishable origins of replication, namely ori1, ori2, ori3, and two genes for replication initiation proteins, RepB and RepA, necessary for the functioning of ori2 or ori3 and ori1, respectively. Plasmids containing ori1 require DNA polymerase I (Pol I) for replication, and those carrying ori2 and ori3 do not require Pol I. Plasmid pJD4 is the smallest plasmid characterized containing three origins of replication and two unique Rep proteins (Pagotto & Dillon, 2001).

Similarly, another plasmid pCU1 (39 kb) belonging to IncN family contains three replication origins, two of which, called oriB and oriS, function in both PolA+ and PolA- hosts, and a third called oriV functions only in PolA+ hosts. It also encodes RepA, which is required by oriB. The oriS can function without RepA and polymerase I, but the iteron region should also be deleted. The three replication origins and RepA protein are localized in a 2053-bp region (Kim et al., 1994). Thus, functionally distinguishable origins in small replicons may be a way of endowing such replicons with a broad host range.

However, there are certain narrow host range plasmids such as F and R6K (IncX), which contain multiple origins. Thus, this feature is not exclusive to BHR plasmids. Plasmid R6K (38 kb) contains three replication origins (α, β, and γ) and encodes for two replication proteins, pir (encoding the π protein for origins α and γ) and bis (Bis for origin β; Mukhopadhyay et al., 1986). Plasmid F (94.5 kb) contains three independent replication regions, RepFIC, RepFIA, and RepFIB. A 9-kb mini-F plasmid that contains the RepFIA region has two origins oriV and oriS and a single replication initiation protein Rep. Replication from oriV when both oriV and oriS are present is bidirectional, whereas replication from oriS when oriV is deleted is unidirectional (Keasling et al., 1992).

Structure of origin

The structure of the origin also plays an important role in governing the host range. The best example is plasmid RK2, which belongs to IncP family. The IncP plasmids (classified in Escherichia coli as IncP and in Pseudomonas as IncP-1) were divided into two subclasses, designated as IncP alpha and IncP beta (Yakobson & Guiney, 1983). The IncP alpha subgroup consists of indistinguishable plasmids R18, R68, RK2, RP1, and RP4 (Pansegrau et al., 1994). IncP-1beta plasmids, example pB10, pKJK10, etc., are known to be highly promiscuous. They have the ability to transfer between and replicate in nearly all species of the Alpha-, Beta- and Gamma proteobacteria.

Broad host range plasmid RK2 (60 kb) consists of a replication origin (oriV) and a TrfA (trans-acting replication function)-encoding gene (Durland & Helinski, 1990). The minimal origin (oriV) possesses five iterons and is functional in E. coli. However, the presence of three additional iterons stabilizes RK2 maintenance in Pseudomonas putida (Schmidhauser et al., 1983). In addition, the region with four DnaA boxes is essential for RK2 replication in E. coli, but is dispensable for replication of the plasmid in P. aeruginosa (Shah et al., 1995; Doran et al., 1999). This suggests that structural elements of origin are employed for BHR plasmid replication and maintenance in different bacterial hosts.

The plasmids isolated from Gram-positive bacteria usually replicate via rolling circle (RC) method and contain a single-stranded origin (sso) and a double-stranded origin (dso). The plasmid-encoded Rep protein makes a site-specific nick at dso and becomes covalently attached to the 5′ phosphate at the nick site. The 3′ OH end acts as a primer for the synthesis of leading strand. The parental strand is converted into double-stranded DNA by replication initiated at sso. Four types of ssos have been identified in RCR plasmids: (i) ssoA, present in several staphylococcal plasmids such as pT181 and pE194 (Gruss et al., 1987; del Solar et al., 1993) (ii) ssoU, described for pUB110 (van der Lelie et al., 1989); (iii) ssoT, commonly found in Bacillus plasmids (Bron et al., 1987), and (iv) ssoW, described for lactococcal plasmid pWV01 (Seegers et al., 1995). The ssoA- and ssoW-type origins are fully active only in their native hosts (te Riele et al., 1986; Gruss et al., 1987). On the other hand, lagging strand replication from the ssoU type origins is very efficient in various Gram-positive bacteria such as Bacillus subtilis, Staphylococcus aureus, Streptococcus pneumoniae, and Lactococcus lactis (Boe et al., 1989; van der Lelie et al., 1989; Kramer et al., 1995; Meijer et al., 1995; Seegers et al., 1995).

The presence of ssoU is an important factor in determining the promiscuity of RC plasmids. It is important to note that the ssoT of pBAA1, which is fully active in B. subtilis and S. aureus (Seery & Devine, 1993), has 69% homology with the ssoU sequence. On the other hand, the extent of homology between ssoU and ssoAs of plasmids pE194 and pLS1 and the ssoW of pWV01, which function efficiently only in their native hosts, is 52%, 50%, and 59%, respectively. Therefore, it is likely that regions that are conserved between ssoU and ssoT but absent in the ssoAs and ssoW are critical for broad host range replication and plasmid promiscuity. Such sequences may be important for interaction with various RNA polymerases, and possibly other host proteins.

The rate of conversion of ssDNA intermediates into double-stranded DNA forms depends upon the efficiency with which the host proteins recognize a given sso. Kramer et al. (1999) determined the molecular basis of the broad host range function of ssoU type origins. They suggested that a strong interaction between the ssoU and RNA polymerase from different bacterial hosts is an important factor in determining the broad host range replication of ssoU-containing RC plasmids.(Kramer et al., 1999).

It is generally believed that inefficient ssDNA conversion rather than lack of expression of the Rep protein is the major factor preventing establishment of plasmids from Gram-positive bacteria in E. coli. Goze and Ehrlich (Goze & Ehrlich, 1980) showed that a hybrid between pC194 and pBR322, the latter containing an efficient lagging strand initiation site for E. coli, is able to replicate in this bacterium under conditions in which pBR322 replication is prevented. The B. thuringiensis plasmid pTX14-3 cannot be established in E. coli, although its Rep protein is expressed in this bacterium from its own promoter (Andrup et al., 1994). The Rep protein of the RC plasmid pKYM, isolated from the Gram-negative bacterium Shigella sonnei, shows a strong homology with Rep proteins of Gram-positive plasmids (Yasukawa et al., 1991). However, instead of an sso which is characteristic for Gram-positive plasmids, pKYM contains a specific Gram-negative lagging strand initiation signal showing 74% identity with the ssDNA conversion signals of the filamentous phages fd, f1, and M13 (Kodaira et al., 1995).

A limited number of Gram-positive plasmids are exceptional in that they are able to replicate in E. coli also. Apparently, in these cases, Rep is functionally expressed and ssDNA molecules are converted to double-stranded plasmid molecules. Their SSOs are probably functional in E. coli.

Replication initiation independent of host initiation factors

Plasmids that do not require host proteins for replication can maintain themselves in many different bacteria. For example, the IncQ plasmids have a broader host range than any other known replicating element in bacteria. The features responsible for this are as follows: initiation of replication, involving DnaA-independent activation of the origin, and a dedicated primase, which is strictly host independent (Meyer, 2009).These plasmids are usually nonconjugative but are mobilizable by a variety of type IV transporters. Moreover, they have high copy number and exhibit reduced metabolic load. The studies have been carried out mostly on RSF1010, R300B, and R1162, which are nearly identical plasmids, isolated from E. coli strain 3, Salmonella enterica serovar Typhimurium, and Pseudomonas aeruginosa, respectively.

Plasmid RSF1010 (8684 bp) contains three novel genes: repA, repB, and repC. The product of the repA gene has ssDNA-dependent ATPase and DNA helicase activity (Scherzinger et al., 1997), repC product binds to the iterons and opens the origin region, creating the entry site for the RepA helicase (Scherzinger et al., 1991), and the repB product encodes a primase. In vivo, a 2.1-kilobase segment of the plasmid, bearing the replication origin, can establish itself as an autonomous replicon if the DNA region carrying the three rep genes is present in the same cell on an independent plasmid (Scherzinger et al., 1984). Thus, BHR plasmids belonging to the IncQ incompatibility group encode three replication proteins that obviate the need for host proteins.

Another example of initiator protein, DnaA, independent replication is shown by IncP plasmids. The initiation events of replication of RK2 in different unrelated bacteria were examined by cloning the genes encoding for the replicative helicase, DnaB, of Pseudomonas putida and Pseudomonas aeruginosa. The respective purified proteins were tested for activity along with E. coli DnaB at RK2 oriV. It was found that all three helicases could be recruited and activated at the RK2 origin in the presence of the host-specific DnaA protein and the TrfA protein. Escherichia coli or P. putida DnaB was active with either TrfA-33 or TrfA-44 (TrfA is expressed as 33 and 44 kDa forms), while P. aeruginosa DnaB required TrfA-44 for activation, suggesting that the two forms are used variably in different hosts (Caspi et al., 2001). The homologs of TrfA44 and TrfA33 identified in other IncP1 plasmids are referred as TrfA1 and TrfA2, respectively. It was demonstrated that TrfA2 and origin were sufficient to confer broad host range to IncP1 plasmids. TrfA1 on the other hand was found to have no role on the long-term persistence, but its presence led to enhanced transformation efficiency and plasmid copy number (Yano et al., 2012). Moreover, for the Pseudomonas spp. helicases, the host DnaA protein was found to be essential for helicase complex formation and activity at oriV (Konieczny & Liberek, 2002). Thus, the helicase loading mechanism is adapted to the genetic background of the specific host bacterium (Caspi et al., 2001).

Plasmid-encoded helicase called PcrA have been reported from Gram-positive bacteria also. They are essential helicases and are required for the RC replication of small multicopy plasmids (Anand et al., 2004). The pcrA gene originally identified as being required for plasmid pT181 replication has been identified in all the Gram-positive bacteria whose genomes have been sequenced so far with an exception of plasmid pC194. The latter has been shown to replicate although at a lower copy number, in E. coli and in this host, its replication is supported by DNA helicase II (UvrD) that has 40% identity to PcrA. It has been reported that interaction between the plasmid initiator proteins and heterologous PcrA helicases may be critical in establishing RC plasmids in different hosts.

Anand et al. (2004) have demonstrated that heterologous PcrA helicases from Bacillus anthracis and Bacillus cereus are capable of unwinding Staphylococcus aureus plasmid pT181 from the initiation-generated nick and promoting in vitro replication of the plasmid. These helicases interact with the RepC initiator protein of pT181. The ability of PcrA helicase to unwind noncognate RC plasmids may contribute to the broad host range replication and dissemination of RC plasmids in Gram-positive bacteria.

Other features

It was observed that BHR IncP plasmids contain few sites for restriction enzymes when compared with narrow host range plasmids, and this has been suggested as a benefit as they can easily overcome the restriction barrier of the host cells (Meyer et al., 1977). Results from the BHR IncQ and IncPα plasmids indicate that increase in copy number can be permitted in some hosts but not in others (Haugan et al., 1995). The topology of the plasmids is also not the same in different hosts. For example, the supercoiling density of plasmids replicating in Bacillus subtilis seems to be lower than in other Gram-positive bacteria (Novick et al., 1986).

Conjugation also plays an important role in the transfer of plasmids. Conjugative plasmids are self-transmissible. They carry the genes necessary for transfer initiation at origin of transfer (OriT) called MOB genes (also called Dtr genes, for DNA transfer replication) and mating-pair apparatus formation (Zatyka and Thomas, 1998). However, a large group of plasmids are nonself-transmissible, but they can be mobilized via a mating apparatus provided by a self-transmissible plasmid (Smillie et al., 2010). An extensive review article from the group of de la Cruz details the entire process of plasmid transfer via conjugation and host range (Smillie et al., 2010).

Thus, the presence of one or more of the above-listed features in a plasmid is likely to impart broad host range capabilities to it (Fig. 1a and b). However, there are certain plasmids, which have broad host range, but the reasons are not known. Plasmid pCR1 and pCR2 isolated from Corynebacterium renale can replicate in E. coli (Srivastava et al., 2006; Walia et al., 2007). Similarly, a 640-bp minimal replicon obtained from the plasmid pool from Acidothiobacillus ferroxidans has been shown to replicate in a number of bacteria (Kalyaeva et al., 2002).

Idealized depiction of a broad host range plasmid originating from a Gram-negative bacteria (a) and Gram-positive bacteria (b). The genes repA, repB, and repC encode for the helicase, primase. and initiator protein. The single-stranded origin ssoU and the PcrA helicase is highlighted, which confers broad host range to Gram-positive bacteria.

Idealized depiction of a broad host range plasmid originating from a Gram-negative bacteria (a) and Gram-positive bacteria (b). The genes repA, repB, and repC encode for the helicase, primase. and initiator protein. The single-stranded origin ssoU and the PcrA helicase is highlighted, which confers broad host range to Gram-positive bacteria.

In an attempt to predict the host range of plasmids, genomic signature method was developed. Trinucleotide composition of the plasmid, which is often similar to the chromosome of the current host, was compared with all completely sequenced bacterial chromosomes. The method was validated by testing on plasmids with known host range. It was found that in the case of IncW, IncP, IncQ, and PromA family of plasmids, the signatures were not similar to any of the chromosomal signatures suggesting that these plasmids have not been ameliorated in any host due to their promiscuous nature (Suzuki et al., 2010).

Molecular basis of broad host range plasmid evolution

Plasmids have been reported to adapt and evolve in an otherwise unfavorable host. The stability of plasmid pB10 (64.5 kb), originally isolated from a wastewater treatment plant in Germany (Schluter et al., 2003), was compared among 19 strains within the Alpha-, Beta- or Gamma-proteobacteria. Ten strains showed no detectable plasmid loss over 200 generations, two strains showed plasmid-free clones only sporadically, and three strains exhibited rapid plasmid loss within 80 generations. Mathematical modeling was carried out, and it was suggested that the variations over time could be due to compensatory mutations (De Gelder et al., 2007). To investigate whether the same plasmid can adapt to unfavorable hosts, evolution experiments were performed, and it was suggested that regular switching between distinct hosts hampers adaptive plasmid evolution. The complete genome sequences of four evolved plasmids where true host range expansion was observed revealed a point mutation in trbC gene that encodes for a putative prepilin involved in mating-pair formation. Thus, it was shown that a BHR plasmid can adapt to an unfavorable host and thereby expand its long-term host range (De Gelder et al., 2008). Interestingly, the same authors revealed that host range of pB10 within an activated-sludge microbial community was significantly influenced by the type of donor strain (De Gelder et al., 2005). In a study by Sota et al. (2010), evolutionary experiments were carried out using IncP1 mini replicon in four different hosts, where the plasmid was reported to be unstable. After 1000 generations, it was found that stability was improved in all the coevolved hosts and in only one case in the ancestral host. Sequencing results showed mutations at the N terminus region of TrfA (Sota et al., 2010). To gain deeper insight, colony PCR and pyrosequencing were carried out on randomly selected colonies up to several generations. Several new mutations in TrfA were observed after 200 generations in novel hosts, but after 1000 generations, only one or two genotypes dominated the population. Thus, clonal interference that is a competition between coexisting hosts with different plasmid genotypes was shown to play an important role in plasmid host adaptation (Hughes et al., 2012). Homologous recombination has been proposed to play an important role in plasmid evolution in the case of IncW (Fernandez-Lopez et al., 2006) and IncP1 (Norberg et al., 2011) and F (Boyd et al., 1996). In yet another study, single amino acid change in RepA of the narrow host range plasmid pPS10 or in E. coli DnaA resulted in expansion of plasmid's replication range (Fernandez-Tresguerres et al., 1995; Maestro et al., 2002, 2003). Studies on plasmid host evolution are limited, and more studies are needed in this direction for predicting the expansion or contraction or shift in the host range of plasmids.

Implications of broad host range plasmids to recombinant DNA technology

The recombinant DNA revolution began in E. coli and evolved rapidly because the well-studied plasmids (ColE1, p15A, and pSC101) and bacteriophage needed little modification for use as recombinant DNA vectors. The vectors, however, have narrow host range. Using broad host range replicons as the basis of cloning, vector development has the advantage that the cloning may be performed by standard techniques in E. coli, which is easy to manipulate, and the recombinant plasmid is subsequently transferred to different experimental hosts, usually by conjugation or electroporation. Historically, three main types of broad host range replicons have been popular for vector construction: RK2 (IncP), RSF1010 (IncQ), and pSa (IncW). Currently, pBBR1 and pWVO1 which can replicate in a wide variety of Gram-negative hosts and Gram-negative bacteria (Davison, 2002) are also used for the same purpose. A few vectors constructed using the replicons obtained from BHR plasmids are listed in Table 2.

Table 2

Vectors constructed using replicons from broad host range plasmids

Name of replicon Name of vector constructed Type of vector Antibiotic resistance Size (kb) Reference 
RK2 pRK290 Cloning vector Tc 20 Ditta et al. (1985
RK2 pLAFR1 Cosmid vector Tc 21.6 Vanbleu et al. (2004
RK2 pLAFR5 Cosmid vector with two cos sites Tc 21.5 Keen et al. (1988
RK2 pRS44 Cloning vector Cm, Km 10.3 Aakvik et al. (2009
RK2 pJB137 Expression vectors Ap 7.6 Blatny et al. (1997
 pJB653  Ap 7.0  
RK2 pGNS-BAC-1 BAC vector Cm 11.9 Kakirde et al. (2011
RK2 pFAJ1700 Expression vector Ap, Tc 10.5 Dombrecht et al. (2001
RSF1010 pDSK509 Cloning vector Km 9.3 Keen et al. (1988
RSF1010 pKT210 Cloning vector Cm 11.8 Bagdasarian et al. (1981
RSF1010 pAYC32 Cloning vectors Ap, Sm 9.7 Chistoserdov & Tsygankov (1986
pAYC39 Ap, Sm, Tc 
pAYC51/52 Cosmid vector Ap, Sm, cos 11.3 
RSF1010 pJFF224-NX Expression vector Cm 7.8 Frey (1992
RSF1010 pQLacZ1 Cloning vector Sm, Sp 17.1 O'Sullivan et al. (2010
pQLacZ2 Sm, Sp 17.9 
pQLacZ3 Cm 16.1 
RSF1010 pHRP309 Promoter probe vector Gm 12 Parales & Harwood (1993
pBBR1 pBHR1 Cloning vector Cm, Km 5.3 Szpirer et al. (2001
pBBR1 pBBR1MCS2 Cloning vector Km 5.1 Kovach et al. (1995
pBBR1MCS3 Tc 5.2 
pBBR1MCS4 Ap 4.9 
pBBR1MCS5 Gm 4.7 
R300B pGSS33 Cloning vector Ap, Cm, Tc, Sm 13.4 Sharpe (1984
R300B pDG105 Cloning vector Km 9.0 Gambill & Summers (1985
R300B pHT128 Cloning vector Cm, Tc 12.5 Takahashi & Watanabe (2002
pWVO1 pBAV1K-T5 Expression vector Km 8.6 Bryksin & Matsumura (2010
Name of replicon Name of vector constructed Type of vector Antibiotic resistance Size (kb) Reference 
RK2 pRK290 Cloning vector Tc 20 Ditta et al. (1985
RK2 pLAFR1 Cosmid vector Tc 21.6 Vanbleu et al. (2004
RK2 pLAFR5 Cosmid vector with two cos sites Tc 21.5 Keen et al. (1988
RK2 pRS44 Cloning vector Cm, Km 10.3 Aakvik et al. (2009
RK2 pJB137 Expression vectors Ap 7.6 Blatny et al. (1997
 pJB653  Ap 7.0  
RK2 pGNS-BAC-1 BAC vector Cm 11.9 Kakirde et al. (2011
RK2 pFAJ1700 Expression vector Ap, Tc 10.5 Dombrecht et al. (2001
RSF1010 pDSK509 Cloning vector Km 9.3 Keen et al. (1988
RSF1010 pKT210 Cloning vector Cm 11.8 Bagdasarian et al. (1981
RSF1010 pAYC32 Cloning vectors Ap, Sm 9.7 Chistoserdov & Tsygankov (1986
pAYC39 Ap, Sm, Tc 
pAYC51/52 Cosmid vector Ap, Sm, cos 11.3 
RSF1010 pJFF224-NX Expression vector Cm 7.8 Frey (1992
RSF1010 pQLacZ1 Cloning vector Sm, Sp 17.1 O'Sullivan et al. (2010
pQLacZ2 Sm, Sp 17.9 
pQLacZ3 Cm 16.1 
RSF1010 pHRP309 Promoter probe vector Gm 12 Parales & Harwood (1993
pBBR1 pBHR1 Cloning vector Cm, Km 5.3 Szpirer et al. (2001
pBBR1 pBBR1MCS2 Cloning vector Km 5.1 Kovach et al. (1995
pBBR1MCS3 Tc 5.2 
pBBR1MCS4 Ap 4.9 
pBBR1MCS5 Gm 4.7 
R300B pGSS33 Cloning vector Ap, Cm, Tc, Sm 13.4 Sharpe (1984
R300B pDG105 Cloning vector Km 9.0 Gambill & Summers (1985
R300B pHT128 Cloning vector Cm, Tc 12.5 Takahashi & Watanabe (2002
pWVO1 pBAV1K-T5 Expression vector Km 8.6 Bryksin & Matsumura (2010

Impact of broad host range plasmids in Environment

Mobile broad host range plasmids significantly contribute to the dissemination of beneficial genetic traits among the population of a certain species and even beyond species boundaries. These include the resistance to antibiotics, metals (Smalla et al., 2006), quaternary ammonium compounds (QACs), and triphenyl methane dyes such as crystal violet, malachite green, and basic fuchsin. (Schluter et al., 2007), degradation of herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D), atrazine, haloacetate, p-toluene sulfsonate, chlorobenzoic acid etc. (Don & Pemberton, 1981, 1985). It was found that wastewater treatment plants are reservoirs for BHR plasmids and from there, they are introduced into streams (Akiyama et al., 2010). They serve as an important tool for interdomain or intergeneric gene transfer by conjugation. Plasmid RSF1010 has been seen as an example of an interdomain gene transfer agent. It can be transferred from Agrobacterium tumefaciens into plant cells in the presence of vir functions in A. tumefaciens. The transfer of RP1 between Erwinia herbiola or P. syringae donors and Erwinia amylovora recipient is an example of intergeneric gene transfer. Thus, BHR plasmids exhibit that gene pools of all the domains are interlinked. (Droge et al., 1998).

Conclusions

Broad host range plasmids can replicate and stably maintain the genes they carry in taxonomically distant species. As such, they represent useful vectors for recombinant DNA technology. Here, we have consolidated several features that are likely to confer broad host range replication and maintenance capabilities to the plasmid. This will be helpful in ascertaining host range properties to the new plasmids. However, for some plasmids, the reasons are not so evident suggesting that there could be some unknown mechanisms governing the host range in those cases. The database of BHR plasmids is limited, and more studies are required. New plasmids from metagenomic studies or from individual cells would probably shed light on the conserved features and newer mechanisms operating related to host–plasmid interaction.

Tribute

Professor J.K. Deb (August 1, 1947–March 14, 2010) obtained his PhD in Chemistry from Banaras Hindu University, India. He did his postdoctoral training at Baylor College of Medicine, Houston, USA. He also worked as a postdoctoral fellow in University of Wisconsin Madison, Madison, USA. He returned to India in 1983 when he joined the Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, India. He produced nine PhD students. As a teacher, he was admired by a vast majority of students. His area of interest was plasmid biology and developing corynebacterial expression systems. He was fascinated by the naturally occurring broad host range plasmids and wanted to continue research in that. This review article is dedicated to him for his contributions to science and for his inspiration to students.

References

Aakvik
T
Degnes
KF
Dahlsrud
R
et al. (
2009
)
A plasmid RK2-based broad-host-range cloning vector useful for transfer of metagenomic libraries to a variety of bacterial species
.
FEMS Microbiol Lett
 
296
:
149
158
.
Akiyama
T
Asfahl
KL
Savin
MC
(
2010
)
Broad-host-range plasmids in treated wastewater effluent and receiving streams
.
J Environ Qual
 
39
:
2211
2215
.
Aleshin
VV
Semenova
EV
Doroshenko
VG
Jomantas
YV
Tarakanov
BV
Livshits
VA
(
1999
)
The broad host range plasmid pLF1311 from Lactobacillus fermentum VKM1311
.
FEMS Microbiol Lett
 
178
:
47
53
.
Anand
SP
Mitra
P
Naqvi
A
Khan
SA
(
2004
)
Bacillus anthracis and Bacillus cereus PcrA helicases can support DNA unwinding and in vitro rolling-circle replication of plasmid pT181 of Staphylococcus aureus
.
J Bacteriol
 
186
:
2195
2199
.
Andrup
L
Damgaard
J
Wassermann
K
Boe
L
Madsen
SM
Hansen
FG
(
1994
)
Complete nucleotide sequence of the Bacillus thuringiensis subsp. israelensis plasmid pTX14-3 and its correlation with biological properties
.
Plasmid
 
31
:
72
88
.
Avison
MB
Walsh
TR
Bennett
PM
(
2001
)
pUb6060: a broad-host-range, DNA polymerase-I-independent ColE2-like plasmid
.
Plasmid
 
45
:
88
100
.
Bagdasarian
M
Lurz
R
Ruckert
B
Franklin
FC
Bagdasarian
MM
Frey
J
Timmis
KN
(
1981
)
Specific-purpose plasmid cloning vectors. II. Broad host range, high copy number, RSF1010-derived vectors, and a host-vector system for gene cloning in Pseudomonas
.
Gene
 
16
:
237
247
.
Bartosik
D
Baj
J
Sochacka
M
Piechucka
E
Wlodarczyk
M
(
2002
)
Molecular characterization of functional modules of plasmid pWKS1 of Paracoccus pantotrophus DSM 11072
.
Microbiology
 
148
:
2847
2856
.
Billington
SJ
Jost
BH
Songer
JG
(
1998
)
The Arcanobacterium (Actinomyces) pyogenes plasmid pAP1 is a member of the pIJ101/pJV1 family of rolling circle replication plasmids
.
J Bacteriol
 
180
:
3233
3236
.
Blatny
JM
Brautaset
T
Winther-Larsen
HC
Haugan
K
Valla
S
(
1997
)
Construction and use of a versatile set of broad-host-range cloning and expression vectors based on the RK2 replicon
.
Appl Environ Microbiol
 
63
:
370
379
.
Boe
L
Gros
MF
te Riele
H
Ehrlich
SD
Gruss
A
(
1989
)
Replication origins of single-stranded-DNA plasmid pUB110
.
J Bacteriol
 
171
:
3366
3372
.
Boyd
EF
Hill
CW
Rich
SM
Hartl
DL
(
1996
)
Mosaic structure of plasmids from natural populations of Escherichia coli
.
Genetics
 
143
:
1091
1100
.
Bron
S
Bosma
P
van Belkum
M
Luxen
E
(
1987
)
Stability function in the Bacillus subtilis plasmid pTA 1060
.
Plasmid
 
18
:
8
15
.
Bryksin
AV
Matsumura
I
(
2010
)
Rational design of a plasmid origin that replicates efficiently in both gram-positive and gram-negative bacteria
.
PLoS ONE
 
5
:
e13244
.
Caspi
R
Pacek
M
Consiglieri
G
Helinski
DR
Toukdarian
A
Konieczny
I
(
2001
)
A broad host range replicon with different requirements for replication initiation in three bacterial species
.
EMBO J
 
20
:
3262
3271
.
Chistoserdov
AY
Tsygankov
YD
(
1986
)
Broad host range vectors derived from an RSF1010::Tn1 plasmid
.
Plasmid
 
16
:
161
167
.
Clewell
DB
Yagi
Y
Dunny
GM
Schultz
SK
(
1974
)
Characterization of three plasmid deoxyribonucleic acid molecules in a strain of Streptococcus faecalis: identification of a plasmid determining erythromycin resistance
.
J Bacteriol
 
117
:
283
289
.
Datta
N
Hedges
RW
(
1972
)
Host ranges of R factors
.
J Gen Microbiol
 
70
:
453
460
.
Davison
J
(
2002
)
Genetic tools for pseudomonads, rhizobia, and other gram-negative bacteria
.
Biotechniques
 
32
:
386
388
, 390, 392–384, passim.
De Gelder
L
Vandecasteele
FP
Brown
CJ
Forney
LJ
Top
EM
(
2005
)
Plasmid donor affects host range of promiscuous IncP-1beta plasmid pB10 in an activated-sludge microbial community
.
Appl Environ Microbiol
 
71
:
5309
5317
.
De Gelder
L
Ponciano
JM
Joyce
P
Top
EM
(
2007
)
Stability of a promiscuous plasmid in different hosts: no guarantee for a long-term relationship
.
Microbiology
 
153
:
452
463
.
De Gelder
L
Williams
JJ
Ponciano
JM
Sota
M
Top
EM
(
2008
)
Adaptive plasmid evolution results in host-range expansion of a broad-host-range plasmid
.
Genetics
 
178
:
2179
2190
.
De Rossi
E
Milano
A
Brigidi
P
Bini
F
Riccardi
G
(
1992
)
Structural organization of pBC1, a cryptic plasmid from Bacillus coagulans
.
J Bacteriol
 
174
:
638
642
.
del Solar
G
Moscoso
M
Espinosa
M
(
1993
)
Rolling circle-replicating plasmids from gram-positive and gram-negative bacteria: a wall falls
.
Mol Microbiol
 
8
:
789
796
.
del Solar
G
Alonso
JC
Espinosa
M
Diaz-Orejas
R
(
1996
)
Broad-host-range plasmid replication: an open question
.
Mol Microbiol
 
21
:
661
666
.
Ditta
G
Schmidhauser
T
Yakobson
E
et al. (
1985
)
Plasmids related to the broad host range vector, pRK290, useful for gene cloning and for monitoring gene expression
.
Plasmid
 
13
:
149
153
.
Dombrecht
B
Vanderleyden
J
Michiels
J
(
2001
)
Stable RK2-derived cloning vectors for the analysis of gene expression and gene function in gram-negative bacteria
.
Mol Plant Microbe Interact
 
14
:
426
430
.
Don
RH
Pemberton
JM
(
1981
)
Properties of six pesticide degradation plasmids isolated from Alcaligenes paradoxus and Alcaligenes eutrophus
.
J Bacteriol
 
145
:
681
686
.
Don
RH
Pemberton
JM
(
1985
)
Genetic and physical map of the 2,4-dichlorophenoxyacetic acid-degradative plasmid pJP4
.
J Bacteriol
 
161
:
466
468
.
Doran
KS
Helinski
DR
Konieczny
I
(
1999
)
Host-dependent requirement for specific DnaA boxes for plasmid RK2 replication
.
Mol Microbiol
 
33
:
490
498
.
Droge
M
Puhler
A
Selbitschka
W
(
1998
)
Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern
.
J Biotechnol
 
64
:
75
90
.
Durland
RH
Helinski
DR
(
1990
)
Replication of the broad-host-range plasmid RK2: direct measurement of intracellular concentrations of the essential TrfA replication proteins and their effect on plasmid copy number
.
J Bacteriol
 
172
:
3849
3858
.
Fernandez-Lopez
R
Garcillan-Barcia
MP
Revilla
C
Lazaro
M
Vielva
L
de la Cruz
F
(
2006
)
Dynamics of the IncW genetic backbone imply general trends in conjugative plasmid evolution
.
FEMS Microbiol Rev
 
30
:
942
966
.
Fernandez-Tresguerres
ME
Martin
M
Garcia de Viedma
D
Giraldo
R
Diaz-Orejas
R
(
1995
)
Host growth temperature and a conservative amino acid substitution in the replication protein of pPS10 influence plasmid host range
.
J Bacteriol
 
177
:
4377
4384
.
Frey
J
(
1992
)
Construction of a broad host range shuttle vector for gene cloning and expression in Actinobacillus pleuropneumoniae and other Pasteurellaceae
.
Res Microbiol
 
143
:
263
269
.
Gambill
BD
Summers
AO
(
1985
)
Versatile mercury-resistant cloning and expression vectors
.
Gene
 
39
:
293
297
.
Goze
A
Ehrlich
SD
(
1980
)
Replication of plasmids from Staphylococcus aureus in Escherichia coli
.
P Natl Acad Sci USA
 
77
:
7333
7337
.
Gruss
AD
Ross
HF
Novick
RP
(
1987
)
Functional analysis of a palindromic sequence required for normal replication of several staphylococcal plasmids
.
P Natl Acad Sci USA
 
84
:
2165
2169
.
Haugan
K
Karunakaran
P
Tondervik
A
Valla
S
(
1995
)
The host range of RK2 minimal replicon copy-up mutants is limited by species-specific differences in the maximum tolerable copy number
.
Plasmid
 
33
:
27
39
.
Horodniceanu
T
Bouanchaud
DH
Bieth
G
Chabbert
YA
(
1976
)
R plasmids in Streptococcus agalactiae (group B)
.
Antimicrob Agents Chemother
 
10
:
795
801
.
Hughes
JM
Lohman
BK
Deckert
GE
Nichols
EP
Settles
M
Abdo
Z
Top
EM
(
2012
)
The role of clonal interference in the evolutionary dynamics of plasmid-host adaptation
.
MBio
 
3
:
e00077
00012
.
Kakirde
KS
Wild
J
Godiska
R
et al. (
2011
)
Gram negative shuttle BAC vector for heterologous expression of metagenomic libraries
.
Gene
 
475
:
57
62
.
Kalyaeva
E
Bass
I
Kholodii
G
Nikiforov
V
(
2002
)
A broad host range plasmid vector that does not encode replication proteins
.
FEMS Microbiol Lett
 
211
:
91
95
.
Kataoka
M
Seki
T
Yoshida
T
(
1991
)
Five genes involved in self-transmission of pSN22, a Streptomyces plasmid
.
J Bacteriol
 
173
:
4220
4228
.
Keasling
JD
Palsson
BO
Cooper
S
(
1992
)
Replication of mini-F plasmids during the bacterial division cycle
.
Res Microbiol
 
143
:
541
548
.
Keen
NT
Tamaki
S
Kobayashi
D
Trollinger
D
(
1988
)
Improved broad-host-range plasmids for DNA cloning in gram-negative bacteria
.
Gene
 
70
:
191
197
.
Kieser
T
Hopwood
DA
Wright
HM
Thompson
CJ
(
1982
)
pIJ101, a multi-copy broad host-range Streptomyces plasmid: functional analysis and development of DNA cloning vectors
.
Mol Gen Genet
 
185
:
223
228
.
Kim
HY
Banerjee
SK
Iyer
VN
(
1994
)
The incN plasmid replicon: two pathways of DNA polymerase I-independent replication
.
J Bacteriol
 
176
:
7735
7739
.
Kodaira
K
Oki
M
Taketo
A
Yasukawa
H
Masamune
Y
(
1995
)
Determination of the single strand origin of Shigella sonnei plasmid pKYM
.
Biochim Biophys Acta
 
1260
:
183
190
.
Konieczny
I
Liberek
K
(
2002
)
Cooperative action of Escherichia coli ClpB protein and DnaK chaperone in the activation of a replication initiation protein
.
J Biol Chem
 
277
:
18483
18488
.
Kovach
ME
Elzer
PH
Hill
DS
Robertson
GT
Farris
MA
Roop
RM
II
Peterson
KM
(
1995
)
Four new derivatives of the broad-host-range cloning vector pBBR1MCS, carrying different antibiotic-resistance cassettes
.
Gene
 
166
:
175
176
.
Kramer
MG
del Solar
G
Espinosa
M
(
1995
)
Lagging-strand origins of the promiscuous plasmid pMV158: physical and functional characterization
.
Microbiology
 
141
(
Pt 3
):
655
662
.
Kramer
MG
Espinosa
M
Misra
TK
Khan
SA
(
1999
)
Characterization of a single-strand origin, ssoU, required for broad host range replication of rolling-circle plasmids
.
Mol Microbiol
 
33
:
466
475
.
Krishnan
BR
Iyer
VN
(
1988
)
Host ranges of the IncN group plasmid pCU1 and its minireplicon in gram-negative purple bacteria
.
Appl Environ Microbiol
 
54
:
2273
2276
.
Kues
U
Stahl
U
(
1989
)
Replication of plasmids in gram-negative bacteria
.
Microbiol Rev
 
53
:
491
516
.
Kulinska
A
Czeredys
M
Hayes
F
Jagura-Burdzy
G
(
2008
)
Genomic and functional characterization of the modular broad-host-range RA3 plasmid, the archetype of the IncU group
.
Appl Environ Microbiol
 
74
:
4119
4132
.
Lacks
SA
Lopez
P
Greenberg
B
Espinosa
M
(
1986
)
Identification and analysis of genes for tetracycline resistance and replication functions in the broad-host-range plasmid pLS1
.
J Mol Biol
 
192
:
753
765
.
Leenhouts
KJ
Tolner
B
Bron
S
Kok
J
Venema
G
Seegers
JF
(
1991
)
Nucleotide sequence and characterization of the broad-host-range lactococcal plasmid pWVO1
.
Plasmid
 
26
:
55
66
.
Maestro
B
Sanz
JM
Faelen
M
Couturier
M
Diaz-Orejas
R
Fernandez-Tresguerres
E
(
2002
)
Modulation of pPS10 host range by DnaA
.
Mol Microbiol
 
46
:
223
234
.
Maestro
B
Sanz
JM
Diaz-Orejas
R
Fernandez-Tresguerres
E
(
2003
)
Modulation of pPS10 host range by plasmid-encoded RepA initiator protein
.
J Bacteriol
 
185
:
1367
1375
.
Meijer
WJ
van der Lelie
D
Venema
G
Bron
S
(
1995
)
Effects of the generation of single-stranded DNA on the maintenance of plasmid pMV158 and derivatives in Lactococcus lactis
.
Plasmid
 
33
:
91
99
.
Meyer
R
(
2009
)
Replication and conjugative mobilization of broad host-range IncQ plasmids
.
Plasmid
 
62
:
57
70
.
Meyer
R
Figurski
D
Helinski
DR
(
1977
)
Physical and genetic studies with restriction endonucleases on the broad host-range plasmid RK2
.
Mol Gen Genet
 
152
:
129
135
.
Meyer
R
Laux
R
Boch
G
Hinds
M
Bayly
R
Shapiro
JA
(
1982
)
Broad-host-range IncP-4 plasmid R1162: effects of deletions and insertions on plasmid maintenance and host range
.
J Bacteriol
 
152
:
140
150
.
Mukhopadhyay
P
Filutowicz
M
Helinski
DR
(
1986
)
Replication from one of the three origins of the plasmid R6K requires coupled expression of two plasmid-encoded proteins
.
J Biol Chem
 
261
:
9534
9539
.
Norberg
P
Bergstrom
M
Jethava
V
Dubhashi
D
Hermansson
M
(
2011
)
The IncP-1 plasmid backbone adapts to different host bacterial species and evolves through homologous recombination
.
Nat Commun
 
2
:
268
.
Novick
RP
Edelman
I
Lofdahl
S
(
1986
)
Small Staphylococcus aureus plasmids are transduced as linear multimers that are formed and resolved by replicative processes
.
J Mol Biol
 
192
:
209
220
.
O'Sullivan
LE
Nickerson
CA
Wilson
JW
(
2010
)
A series of IncQ-based reporter plasmids for use in a range of Gram negative genera
.
J Microbiol Biotechnol
 
20
:
871
874
.
Pagotto
F
Dillon
JA
(
2001
)
Multiple origins and replication proteins influence biological properties of beta-lactamase-producing plasmids from Neisseria gonorrhoeae
.
J Bacteriol
 
183
:
5472
5481
.
Pansegrau
W
Lanka
E
Barth
PT
et al. (
1994
)
Complete nucleotide sequence of Birmingham IncP alpha plasmids. Compilation and comparative analysis
.
J Mol Biol
 
239
:
623
663
.
Parales
RE
Harwood
CS
(
1993
)
Construction and use of a new broad-host-range lacZ transcriptional fusion vector, pHRP309, for gram- bacteria
.
Gene
 
133
:
23
30
.
Sakai
H
Komano
T
(
1996
)
DNA replication of IncQ broad-host-range plasmids in gram-negative bacteria
.
Biosci Biotechnol Biochem
 
60
:
377
382
.
Scherzinger
E
Bagdasarian
MM
Scholz
P
Lurz
R
Ruckert
B
Bagdasarian
M
(
1984
)
Replication of the broad host range plasmid RSF1010: requirement for three plasmid-encoded proteins
.
P Natl Acad Sci USA
 
81
:
654
658
.
Scherzinger
E
Haring
V
Lurz
R
Otto
S
(
1991
)
Plasmid RSF1010 DNA replication in vitro promoted by purified RSF1010 RepA, RepB and RepC proteins
.
Nucleic Acids Res
 
19
:
1203
1211
.
Scherzinger
E
Ziegelin
G
Barcena
M
Carazo
JM
Lurz
R
Lanka
E
(
1997
)
The RepA protein of plasmid RSF1010 is a replicative DNA helicase
.
J Biol Chem
 
272
:
30228
30236
.
Schluter
A
Heuer
H
Szczepanowski
R
Forney
LJ
Thomas
CM
Puhler
A
Top
EM
(
2003
)
The 64 508 bp IncP-1beta antibiotic multiresistance plasmid pB10 isolated from a waste-water treatment plant provides evidence for recombination between members of different branches of the IncP-1beta group
.
Microbiology
 
149
:
3139
3153
.
Schluter
A
Szczepanowski
R
Puhler
A
Top
EM
(
2007
)
Genomics of IncP-1 antibiotic resistance plasmids isolated from wastewater treatment plants provides evidence for a widely accessible drug resistance gene pool
.
FEMS Microbiol Rev
 
31
:
449
477
.
2Schmidhauser
TJ
Filutowicz
M
Helinski
DR
(
1983
)
Replication of derivatives of the broad host range plasmid RK2 in two distantly related bacteria
.
Plasmid
 
9
:
325
330
.
Seegers
JF
Zhao
AC
Meijer
WJ
Khan
SA
Venema
G
Bron
S
(
1995
)
Structural and functional analysis of the single-strand origin of replication from the lactococcal plasmid pWV01
.
Mol Gen Genet
 
249
:
43
50
.
Seery
L
Devine
KM
(
1993
)
Analysis of features contributing to activity of the single-stranded origin of Bacillus plasmid pBAA1
.
J Bacteriol
 
175
:
1988
1994
.
Shah
DS
Cross
MA
Porter
D
Thomas
CM
(
1995
)
Dissection of the core and auxiliary sequences in the vegetative replication origin of promiscuous plasmid RK2
.
J Mol Biol
 
254
:
608
622
.
Sharpe
GS
(
1984
)
Broad host range cloning vectors for gram-negative bacteria
.
Gene
 
29
:
93
102
.
Smalla
K
Haines
AS
Jones
K
Krogerrecklenfort
E
Heuer
H
Schloter
M
Thomas
CM
(
2006
)
Increased abundance of IncP-1beta plasmids and mercury resistance genes in mercury-polluted river sediments: first discovery of IncP-1beta plasmids with a complex mer transposon as the sole accessory element
.
Appl Environ Microbiol
 
72
:
7253
7259
.
Smillie
C
Garcillan-Barcia
MP
Francia
MV
Rocha
EP
de la Cruz
F
(
2010
)
Mobility of plasmids
.
Microbiol Mol Biol Rev
 
74
:
434
452
.
Sota
M
Yano
H
Hughes
JM
Daughdrill
GW
Abdo
Z
Forney
LJ
Top
EM
(
2010
)
Shifts in the host range of a promiscuous plasmid through parallel evolution of its replication initiation protein
.
ISME J
 
4
:
1568
1580
.
Srivastava
P
Nath
N
Deb
JK
(
2006
)
Characterization of broad host range cryptic plasmid pCR1 from Corynebacterium renale
.
Plasmid
 
56
:
24
34
.
Strzelecki
AT
Goodman
AE
Rogers
PL
(
1987
)
Behavior of the IncW plasmid Sa in Zymomonas mobilis
.
Plasmid
 
18
:
46
53
.
Suzuki
H
Yano
H
Brown
CJ
Top
EM
(
2010
)
Predicting plasmid promiscuity based on genomic signature
.
J Bacteriol
 
192
:
6045
6055
.
Szpirer
CY
Faelen
M
Couturier
M
(
2001
)
Mobilization function of the pBHR1 plasmid, a derivative of the broad-host-range plasmid pBBR1
.
J Bacteriol
 
183
:
2101
2110
.
Takahashi
H
Watanabe
H
(
2002
)
A broad-host-range vector of incompatibility group Q can work as a plasmid vector in Neisseria meningitidis: a new genetical tool
.
Microbiology
 
148
:
229
236
.
te Riele
H
Michel
B
Ehrlich
SD
(
1986
)
Are single-stranded circles intermediates in plasmid DNA replication?
EMBO J
 
5
:
631
637
.
Thomas
CM
Hussain
AA
Smith
CA
(
1982
)
Maintenance of broad host range plasmid RK2 replicons in Pseudomonas aeruginosa
.
Nature
 
298
:
674
676
.
Top
EM
Van Daele
P
De Saeyer
N
Forney
LJ
(
1998
)
Enhancement of 2,4-dichlorophenoxyacetic acid (2,4-D) degradation in soil by dissemination of catabolic plasmids
.
Antonie Van Leeuwenhoek
 
73
:
87
94
.
Van der Auwera
GA
Krol
JE
Suzuki
H
et al. (
2009
)
Plasmids captured in C. metallidurans CH34: defining the PromA family of broad-host-range plasmids
.
Antonie Van Leeuwenhoek
 
96
:
193
204
.
van der Lelie
D
Bron
S
Venema
G
Oskam
L
(
1989
)
Similarity of minus origins of replication and flanking open reading frames of plasmids pUB110, pTB913 and pMV158
.
Nucleic Acids Res
 
17
:
7283
7294
.
Vanbleu
E
Marchal
K
Vanderleyden
J
(
2004
)
Genetic and physical map of the pLAFR1 vector
.
DNA Seq
 
15
:
225
227
.
Walia
R
Deb
JK
Mukherjee
KJ
(
2007
)
Development of expression vectors for Escherichia coli based on the pCR2 replicon
.
Microb Cell Fact
 
6
:
14
.
Yakobson
E
Guiney
G
(
1983
)
Homology in the transfer origins of broad host range IncP plasmids: definition of two subgroups of P plasmids
.
Mol Gen Genet
 
192
:
436
438
.
Yano
H
Deckert
GE
Rogers
LM
Top
EM
(
2012
)
Roles of long and short replication initiation proteins in the fate of IncP-1 plasmids
.
J Bacteriol
 
194
:
1533
1543
.
Yasukawa
H
Hase
T
Sakai
A
Masamune
Y
(
1991
)
Rolling-circle replication of the plasmid pKYM isolated from a gram-negative bacterium
.
P Natl Acad Sci USA
 
88
:
10282
10286
.
Zatyka
M
Thomas
CM
(
1998
)
Control of genes for conjugative transfer of plasmids and other mobile elements
.
FEMS Microbiol Rev
 
21
:
291
319
.
Zhang
Y
Praszkier
J
Hodgson
A
Pittard
AJ
(
1994
)
Molecular analysis and characterization of a broad-host-range plasmid, pEP2
.
J Bacteriol
 
176
:
5718
5728
.

Author notes

Article written in memory of the late Prof. J.K. Deb who always used to inspire a lot.
Editor: Hermann Heipieper