Diversity of phage infection types and associated terminology: the problem with ‘Lytic or lysogenic’

Bacteriophages, or phages, are viruses of members of domain Bacteria. These viruses play numerous roles in shaping the diversity of microbial communities, with impact differing depending on what infection strategies specific phages employ. From an applied perspective, these especially are communities containing undesired or pathogenic bacteria that can be modified through phage-mediated bacterial biocontrol, that is, through phage therapy. Here we seek to categorize phages in terms of their infection strategies as well as review or suggest more descriptive, accurate or distinguishing terminology. Categories can be differentiated in terms of (1) whether or not virion release occurs (productive infections versus lysogeny, pseudolysogeny and/or the phage carrier state), (2) the means of virion release (lytic versus chronic release) and (3) the degree to which phages are genetically equipped to display lysogenic cycles (temperate versus non-temperate phages). We address in particular the use or overuse of what can be a somewhat equivocal phrase, ‘Lytic or lysogenic’, especially when employed as a means of distinguishing among phages types. We suggest that the implied dichotomy is inconsistent with both modern as well as historical understanding of phage biology. We consider, therefore, less ambiguous terminology for distinguishing between ‘Lytic’ versus ‘Lysogenic’ phage types.

lytic phage, obligately lytic, phage therapy, professionally lytic, strictly lytic, temperate phage

INTRODUCTION

In this minireview we consider the diversity of phage types as based on potential infection strategies, particularly productive or lysogenic along with lytic release versus chronic release, with emphasis on what major variants should be called (see Table 1 for glossary of terms). In a few of these cases, efforts towards naming do not appear to have been a priority within the community. In other cases, perhaps too many names exist, at least some of which are less precise than may be desirable. We place particular emphasis on addressing what we will argue is common misuse of the phrase, ‘Lytic or lysogenic’, as a means of distinguishing non-temperate from temperate phages. We begin, however, with a scheme for classifying phages, in terms of infection strategies, into four distinct categories: (I) lytic and non-temperate, (II) chronic and non-temperate, (III) lytic and temperate or (IV) chronic and temperate.

Table 1.

Glossary of terms.

Term	Statesa	Phagesb	Categoryc	Definition as employed here
Clear mutant		λ mutant	I	Mutated temperate phage that as a consequence is unable to display lysogenic cycles and thus forms clear rather than turbid plaques
Chronic	D	M13, CTXΦ	II, IV	Productive infections in which virions are released over long intervals without substantial disruption of host cells
Chronic phage	D	M13, CTXΦ	II, IV	Phage whose productive infection is chronic (may or may not be a temperate phage)
Chronic temperate phage	P,V,D	CTXΦ	IV	Chronic phage that is able to display lysogenic cycles, i.e. during which virions are neither produced nor released
Encapsidated during release	D	M13, CTXΦ	II, IV	Referring to virion maturation during release, e.g. as seen with filamentous phages
Encapsidated intracellularly	B	T4, λ	I, III	Referring to virion maturation prior to release, e.g. as seen with tailed phages
Free phage	F	All	All	Mature virion that is extracellularly located
Induction	V	λ, CTXΦ	III, IV	Intracellular transition of a lysogenic infection to a productive infection
Latent infection	P	λ, CTXΦ	III, IV	For bacteriophages, these predominantly are lysogenic infections
Lysogenic cycle	P	λ, CTXΦ	III, IV	Phage replication as a prophage that does not directly result in virion production or release
Lysogenic infection	P	λ, CTXΦ	III, IV	Ongoing phage existence as a prophage
Lysogen	P	λ, CTXΦ	III, IV	Bacterium that is latently infected with a temperate phage
Lysogenic (current def.)	P	λ, CTXΦ	III, IV	Property of a bacterium indicating that it is hosting a prophage/lysogenic cycle
Lysogenic (historical def.)		λ	III	Property of a bacterium indicating an ability to release factors that are able to lyse other bacterial cultures
Lysogenic (literal def.)		T4, λ	I, III	Ability to generate lysis in bacterial cultures
Lysogeny	P	λ, CTXΦ	III, IV	A prophage-containing latent phage infection
Lytic	B	T4, λ	I, III	Productive infections in which phage virions are released over short intervals with lethal disruption of host cells
Lytic cycle	B	T4, λ	I, III	Vegetative phage replication that ends with lysis
Lytic infection	B	T4, λ	I, III	Productive infection in which virions are released via host-cell lysis
Lytic phage	B	T4, λ	I, III	Phage whose productive infection is lytic (may nor may not be a temperate phage)
Lytic temperate phage	P,V,B	λ	III	Lytic phage that is able to display lysogenic cycles
Non-temperate	V	T4, M13	I, II	Description of a phage that is unable to display lysogenic cycles
Obligately lytic	B	T4	I	Phage that upon infection is inherently unable to display lysogenic cycles or chronic release
Obligately productive	B	T4, M13	I, II	Phage that upon infection is inherently unable to display lysogenic cycles
Productive cycle	V	All	All	Vegetative phage replication associated with either chronic or lytic release
Productive infection	V	All	All	Product of either adsorption or induction involving vegetative state and subsequent phage release
Professionally lytic	B	T4	I	Phage that is both obligately lytic and not recently descended from a temperate ancestor
Prophage	P	λ, CTXΦ	III, IV	Phage genome as it exists during lysogenic cycles
Pseudolysogeny				Latent infection during which neither phage genome replication nor prophage formation occurs; other definitions exist and in some cases the phrase ‘carrier state’ has been used synonymously
Strictly lytic	B	T4	I	Used synonymously with obligately lytic
Temperate	P,V	λ, CTXΦ	III, IV	Description of a phage that is able to display lysogenic cycles
Unencapsidated		All	All	An intracellular phage genome that has not been packaged into a virion particle
Vegetative	V	All	All	Replicating phage genome that is not a prophage (contrast both lysogenic and pseudolysogenic)
Virulence	B			Description of ability of phage populations to lyse cultures of bacterial hosts
Virulent	B	T4	I	Often used synonymously with obligately lytic
Virulent mutant	B	λ mutant	I	Clear temperate phage mutant that can form plaques even on lysogens formed by the phage wild-type parent

a

‘States’ refers to distinguishing characteristics as abbreviated throughout the manuscript: ‘B’ refers to phage genome packaging and virion maturation that occurs Before virion release (property of lytic phages only), ‘D’ refers to phage genome packaging and virion maturation that occurs During virion release (property of chronic phages only), ‘F’ refers to Free phages, ‘P’ refers to existence as a Prophage (a property only of temperate phages), ‘V’ refers to display of a Vegetative phase. Vegetative phases are a property of all productive phage infections, though to avoid clutter this is mostly not explicitly indicated in the table. Either B or D states also are properties of all productive phage infections as too, post infection, is the F state. The sequence ‘P,V’ indicates the existence of either Prophage or Vegetative states. P and V will not occur simultaneously during the same infection though can occur sequentially, particularly P → V, which then will proceed through B or D states depending on the phage, culminating in all cases, post successful productive infection, in an F state.

b

Example phages are as discussed in the main text.

c

Categories are ‘I’ meaning lytic and non-temperate, ‘II’ meaning chronic and non-temperate, ‘III’ meaning lytic and temperate and ‘IV’ meaning chronic and temperate.

Strategies of phage infection and release

Phages can be defined as semi-autonomous genetic elements that at some point in their life cycles exist as encapsidated genomes, particularly infectious capsids that are not found within the bounds of host cells. Most viruses can be defined similarly, though especially fungal viruses (mycoviruses) do not necessarily exist as host-unassociated virions or, in a few instances, even as encapsidated genomes (Hyman and Abedon 2012). Here, however, our emphasis primarily is on bacteriophages.

Phages, in terms of their encapsidation and location, can exist in three possible states: (1) intracellularly and unencapsidated, (2) intracellularly and packaged within mature virions or (3) both encapsidated and extracellular. The first state (1) can be further subdivided into what can be described as a “Vegetative phase” (Lwoff 1953), or productive cycle, versus existing as a prophage, that is, instead displaying a lysogenic cycle. The second state (2) can be distinguished from phage genomes that instead are not packaged until the virion release step. The third state (3) consists of free phages, that is, assembled virions that are no longer found within their bacterial host. Abbreviations used henceforward to describe these different states include V for Vegetative phase, P for Prophage, B for genome packaging into mature virions Before release, D for genome packaging into mature virions During release and F for Free phages.

To distinguish among phages, but intentionally without using more standard terms as otherwise are under discussion, we categorize phages into four distinct types using the abbreviations introduced at the end of the previous paragraph. These are

• ‘V → B → F’ phages

• ‘V → D → F’ phages

• ‘V or P → B → F’ phages

• ‘V or P → D → F’ phages

The phrase ‘V or P’ is intended to imply that these phages can display either V- or, instead, P- and then V-type infection states, i.e. Vegetative or Prophage states (Table 1). Productive infections, ones which produce Free phage virions (‘F’), can be contrasted with infections that instead may be described as ‘Reductive’ (Lwoff 1953), particularly lysogenic infections (‘P’) but also, though not otherwise considered here, pseudolysogenic ones (Miller and Day 2008; Abedon 2009; Abedon, Duffy and Turner 2009; Los and Wegrzyn 2012).

In more familiar terms, the phage types described above and in Fig. 1 thus include the following: (I) lytic phages that do not display lysogenic cycles (‘V → B → F’ phages), (II) chronically released phages that do not display lysogenic cycles (‘V → D → F’), (III) lytic phages that can display lysogenic cycles (i.e. temperate phages; ‘V or P → B → F’) and (IV) chronically released phages also that can display lysogenic cycles (which are temperate phages as well; ‘V or P → D → F’). In other words, we can contrast phage types into lytic versus chronic (‘B’ versus ‘D’ phages) as well as not-temperate versus temperate (‘V-only’ versus ‘V or P’ phages). See Table 1 and Table 2 for further consideration.

Figure 1.

Distinguishing among phage states. Intracellularly and unencapsidated, phages can exist in Vegetative versus Prophage forms. Maturation of virion particles can be completed either Before or During virion release (corresponding to lytic versus chronic release, respectively). Lytic phages here are indicated as tailed. Though most tailless phages likely are lytic phages as well, members of phage families Inoviridae and Plasmaviridae are exceptions. Chronically released phages are indicated as filamentous, i.e. members of phage family Inoviridae. The four categories of phage types, as indicated with I, II, III or IV to the left of the figure, are named to the right, with the list found at the top and corresponding to ‘I’ consisting of multiple synonyms for ‘Lytic, non-temperate’.

Table 2.

Distinguishing among different phage types in terms of basic phage infection properties.^a

Phage types (below; characteristics to right)	Vb	Pc	V or P → Vd	Be	Df	Fg
All phages (I, II, III or IV)	+	±	±	±	±	+
Obligately Productive (I or II)h	+	−	±	±	±	+
Chronic (II or IV)	+	±	±	−	+	+
Obligately Chronic (II)i	+	−	±	−	+	+
Lytic (I or III)	+	±	±	+	−	+
Obligately or Strictly Lytic (I)	+	−	±	+	−	+
Professionally Lytic (I)	+	−	−	+	−	+
Virulent, meaning Obligately Lytic (I)	+	−	±	+	−	+
Virulent, meaning Highly Destructive of Cultures (I)j	+	−	±	+	−	+
Virulent, meaning Mutant of a Temperate Phage (I)	+	−	+	+	−	+
Temperate (III or IV)	+	+	×	±	±	+

a

‘+’ implies always a characteristic of, ‘−’ implies never a characteristic of and ‘±’ implies may or may not be a characteristic of.

b

Can exist in a Vegetative state, which is a reproductive, non-prophage, bacterium-infecting, phage genome.

c

Can exist as a prophage, at least for a given host and conditions; distinguishes temperate (+) from non-temperate (−) phages.

d

Mutant and/or descendant of temperate phage, one that no longer can display lysogenic cycles; distinguishes obligately productive descendants of temperate phages (+) from either obligately productive phages that are not descendants of temperate phages (−) or that simply are temperate phages themselves and therefore not obligately productive (×).

e

Exists as a mature virion prior to release from host bacteria; distinguishes chronic (−) from lytic (+) phages.

f

Does not exist as a mature virion prior to release from host bacteria; distinguishes chronic (+) from lytic (−) phages.

g

Exists as a free phage at some point in life cycle.

h

Not a commonly used descriptor.

i

Not a commonly used descriptor.

j

In this case the culture in question is assumed to consist exclusively of bacteria that do not support lysogenic infections by the phage in question, even if that phage is capable of displaying lysogenic infections when infecting different bacterial strains.

Example phages

Examples of obligately lytic phages (category I) include Max Delbrück's well-studied tailed phages T1-T7 (Abedon 2000), with phage T4 the most thoroughly studied (Karam 1994; Miller et al.2003). While tailed phages are always lytic, they are not always obligately lytic (i.e. see category III, below). RNA-genomed phages of families Leviviridae (van Duin and Tsareva 2006) and Cystoviridae (Mindich 2006) we can speculate are consistently obligately lytic. The Microviridae (Fane et al.2006), however, may include members which are not obligately lytic (Krupovic and Forterre 2011). Note that there exists as well variation on how lysis is induced by various lytic phages (Young 2014).

Phage M13 is one of the best studied category II phages (non-temperate, chronic) (Russel and Model 2006). As with lysis, the mechanisms by which chronic release occurs varies among phages, i.e. via extrusion as seen with phage family Inoviridae (Russel and Model 2006) versus via budding as seen with phage family Plasmaviridae (Maniloff and Dybvig 2006).

Phage λ is the most intensely studied of the tailed, temperate phages (Hendrix et al.1983; Ptashne 2004; Casjens and Hendrix 2015) and thereby is representative of category III.

Phage CTXΦ (Mai-Prochnow et al.2015), which encodes the cholera toxin, is the most prominent example of category IV, though with additional members of phage family Inoviridae also thought to be temperate (Yamada et al.2007). In addition, mycoplasma phage L2, a member of phage family Plasmaviridae (Maniloff and Dybvig 2006), has been described as temperate (Maniloff, Kampo and Dascher 1994).

See Abedon (2008) and Abedon, Duffy and Turner (2009) for additional discussion of phage types distinguished by infection characteristics as well as Calendar and Abedon (2006) for numerous individual reviews of specific phage types. See Table 1 for association of these phage types with specific terms and concepts as considered in this minireview.

Lytic or lysogenic

Use of the phrase ‘Lytic or lysogenic’ as a means of distinguishing among phage types may be becoming increasingly common (e.g. see the following paragraph for its use in publications). This we believe is of concern particularly during discussions of the medical procedure known as a phage therapy (e.g. Kutter et al.2010; Abedon et al.2011; Abedon 2015), which as typically practiced tends to strive to avoid using phages that can be categorized into types II, III or IV, i.e. phages that are not obligately lytic. In this section we therefore strive to illuminate the problems associated with the dichotomy of ‘Lytic or lysogenic’, particularly as a means of distinguishing among phage types (‘phage’ or ‘phages’, etc. in the searches below), even if the intended meaning is not altogether lost.

Using Google Scholar, a search on ‘lytic or lysogenic phage’ OR ‘lytic or lysogenic phages’ OR ‘lytic or lysogenic bacteriophage’ OR ‘lytic or lysogenic bacteriophages’ (with quotation marks) yielded 36 results. The dates of these results are 2015 (four results), 2014 (six), 2013 (six), 2012 (four), 2011 (four), 2010 (one), 2009 (two), 2007 (three), 2005 (two), 2002 (one), 1989 (one), 1984 (one) and 1967 (one), that is, most of this usage is fairly recent. At least one of these results, in 2015, refers, however, to a ‘lytic or lysogenic phage life cycle’ (emphasis added). By comparison, a Google Scholar search on ‘lytic or lysogenic cycle’ OR ‘lytic or lysogenic cycles’ yields a total of 101 results. By decades, numbers are 2006–2015 (65 results), 1996–2005 (23), 1986–1995 (six), and then two additional results from 1968. Both phrases thus appear to be becoming increasingly part of the phage biology vernacular.

Part of the problem with use of the phrase, ‘Lytic or lysogenic’, is that bacteria can be lysogenic while phages instead can be temperate, but not vice versa (see Fig. 2 for an exploration of the history of the usage of ‘Lysogenic phage’ versus ‘Temperate phage’). Thus, from Lwoff (1953), p. 271 (emphasis his): ‘Lysogeny is the hereditary power to produce bacteriophage. A lysogenic bacterium is a bacterium possessing and transmitting the power to produce bacteriophage. Each bacterium of a lysogenic strain gives rise to a lysogenic clone…’ Also from Lwoff (1953), p. 273 (emphasis his): ‘The power to lysogenize is the property of temperate phages…’ The vast majority of temperate phages in addition display ‘Lytic’ cycles when productively infecting, that is, rather than chronically releasing virion progeny, hence the term, ‘Lysogenic’, to describe them. What, then, is meant when contrasting ‘Lytic’ with ‘Lysogenic’?

Figure 2.

Comparison of per-year usage of ‘Lysogenic phage(s)’ (red filled, lower curve) versus ‘Temperate phage(s)’ (green filled, upper curve). Though ‘Temperate phage(s)’ currently is used approximately twice as often as ‘Lysogenic phage(s)’, in fact in modern times it was only in the late 1990s that this relative frequency was reached, suggesting a greater preference for ‘Temperate phage(s)’ over ‘Lysogenic phage(s)’ over the roughly 40-year span from the mid-1950s through to the mid-1990s. Similar trends were observed when ‘…phage…’ and ‘…bacteriophage…’ were simultaneously searched on. From 1920 through 1951, however, there are just 12 instances of ‘Lysogenic phage(s)’ or ‘Lysogenic bacterophage(s)’ but only a single instance of ‘Temperate phage(s)’ or ‘Temperate bacterophage(s)’, the latter dating from 1948 and approximately coinciding at least temporally with the discovery of prophage induction (Lwoff 1966).

Though most temperate phages during productive cycles release virions via lysis—that is, during lytic cycles—nonetheless in all likelihood the intended use of ‘Lytic’ in ‘Lytic or lysogenic’ as descriptions of phage types is as shorthand for the ‘V → B → F’ (I) phages, that is, lytic, non-temperate phages. The term ‘Virulent’, however, is often employed preferentially to ‘Lytic, non-temperate’ (Lwoff 1953), thus, ‘Virulent or lysogenic’ might be employed rather than ‘Lytic or lysogenic’. Unfortunately, the term virulent has had multiple meanings over the years with regard to phages (next section). To avoid this issue, it can be preferable, for example, to use the phrase ‘Obligately lytic’ instead of ‘Virulent’ to describe lytic, non-temperate phages. As an aside, note that ‘obligatorily lytic’ (in quotation marks) yields 26 Google Scholar results versus 142 for ‘obligately lytic’.

There exist additional terms that can be used equivalently to ‘Obligately lytic’. These include ‘Strictly lytic’ (which in a within-quotes Google Scholar search yields 223 results), ‘Obligate lytic’ (113 Google Scholar results), ‘Professionally lytic’ (10 results, e.g. Brüssow and Kutter 2005; Kutter 2008; Henein 2013; Kutter et al.2013; Miroshnikov et al.2014), ‘Professionally virulent’ (Górski et al.2009) and ‘Professional virulent’ (nine results, e.g. Brüssow 2005; Brüssow and Kutter 2005; Brüssow 2007; Letarov and Kulikov 2009; Weiss et al.2009; Letarov, Golomidova and Tarasyan 2010; Sarker et al.2012; Bourdin et al.2014). All of these terms are preferable to simply ‘Lytic’ when describing phages, unless one is intentionally referring simultaneously to category I phages (‘V → B → F’, i.e. strictly lytic) and category III phages (‘V or P → B → F’, i.e. temperate phages that can display both lytic and lysogenic cycles). That is, the phrase ‘Lytic phage’ (with 6080 Google Scholar results for a ‘lytic phage’ OR ‘lytic phages’ search) distinguishes among phages particularly in terms of their mode of virion release, lytic rather than chronic, rather than in terms of their ability to display lysogenic cycles. These various phage descriptors and others are summarized in Table 1. (For completeness, note that a ‘chronic phage’ OR ‘chronic phages’ search yields 49 Google Scholar results.)

Further arguments against ‘Virulent’

The term ‘Virulence’ can be used as a description of those phages that are particularly adept at inflicting substantial destruction on their host (Smith, Huggins and Shaw 1987). Within a historical context, this is as occurs primarily to bacterial cultures rather than specifically to individual bacterial cells (Summers 1991). Phages that are less adept at lysing bacterial cultures therefore can be described as being less ‘Virulent’. These can include both temperate phages and also chronically released phages, though the latter are not an emphasis of this section. In the case of temperate phages, this lower virulence occurs because a subset of individual phage infections display lysogenic rather than lytic cycles. The resulting bacterial lysogens also tend to be insensitive to attempts at lytic infection by the same phage types that are lysogenically infecting them—due to display of superinfection immunity (Hershey and Dove 1983; Fogg et al.2010; Hyman and Abedon 2010; Casjens and Hendrix 2015)—and therefore are inclined to resist phage-mediated clearance.

A further complication on the term, ‘Virulent’, is that otherwise temperate phages that are genetically defective in their ability to lysogenize are described as virulent mutants (Lwoff 1953) (2240 Google Scholar results for ‘virulent mutant’ OR ‘virulent mutants’; though refining the search to include the term ‘phage’, not in quotes, yields only 1140 results). Virulence, of course, began as a term that was not specific to phage biology and which, according to the Oxford Dictionary, dates back at least to the 1800s in the English language. ‘Virulent’ was then legitimately coopted close to the beginning of the study of phage biology to describe phages that in a traditional sense are indeed more virulent, at least against bacterial cultures. The term then came to be used to a large extent as a description of phages that do not display lysogenic cycles and which otherwise are lytic, including as referring to virulent mutants of otherwise temperate phages (Ptashne 2004).

The term ‘Obligately lytic’, or ‘Strictly lytic’, etc., contrasting the ambiguity of ‘Virulent’, is meant to explicitly imply an unavoidable display of lytic, productive cycles upon successful infection (Abedon 2008). The term ‘Obligately productive’, though almost never used (no PubMed hits and no Google Scholar hits that are not associated with one of us), would imply a similarly requisite display of either lytic or chronic infections, depending on the phage, rather than referring exclusively to lytic infections, as is implied by ‘Obligately lytic’. Consider also ‘Obligately chronic’ (Table 2). All of these terms can be viewed as more-precise alternatives to the concept of ‘Virulent’ to describe phages that are not temperate. In addition, note that obligately lytic phages may or may not be recent descendants of temperate phages and thus may or may not represent virulent mutants.

Within this framework, what then is meant by ‘Lytic or lysogenic’? This question is particularly relevant within the context of phage therapy where ‘Lytic’ phages typically are considered to be preferable to ‘Lysogenic’ ones. One simple answer could be that ‘Lytic’ is being used equivalently to ‘Obligately lytic’ or ‘Strictly lytic’ as a substitute for ‘Virulent’. Such usage can be problematic, however, since with phage therapy a temperate phage ancestry can be of concern, even if lysogenic cycles themselves do not occur, since temperate phages especially have been shown to carry bacterial virulence factor genes (Hyman and Abedon 2008; Kuhl, Hyman and Abedon 2012; Christie et al.2012). In response to this concern, one could replace ‘Lytic’—in ‘Lytic or lysogenic’—with the phrase, ‘Virulent meaning obligately lytic but nevertheless not a virulent mutant of a temperate phage’. Obviously, however, such phrasing is too complex to become a part of everyday practice. Instead, and perhaps ideally, one might, for example, use the otherwise somewhat underutilized ‘Professionally lytic’ to specifically describe those phages that are both obligately lytic and not closely related to temperate phages, that is, lytic phages that are both not temperate and not virulent mutants of temperate phages (Curtright and Abedon 2011). This perspective we summarize in Fig. 3.

Figure 3.

Proposed usage. ‘Temperate phage’ is always preferable to ‘Lysogenic phage’. ‘Virulent mutant’ is not controversial. ‘Professionally lytic’ we support for the usage as indicated. ‘Strictly lytic’ might be employed equivalently though is insufficiently robust, we feel, in conveying the latter's meaning. ‘Obligately lytic’ or ‘Strictly lytic’ we suggest may be employed as the more general term for ‘Lytic and not temperate’, with ‘Virulent mutant’ or ‘Professionally lytic’ employed when greater specificity is desired.

Lytic and Lysogenic

As alternatives to ‘Lytic or lysogenic’, we thus can have ‘Non-temperate or temperate’, ‘Virulent or temperate’, ‘Obligately lytic or temperate’, ‘Strictly lytic or temperate’, ‘Virulent mutant or temperate’ and/or ‘Professionally lytic or temperate’. ‘Lytic or temperate’, by contrast, does not really work, despite the increasing popularity of ‘Lytic or lysogenic’ as a description of phage types, since most temperate phages, as noted, are also lytic phages. Nonetheless, what all of these alternative phrases have in common is their use of the term, ‘Temperate’, and this is rather than ‘Lysogenic’. What is the justification for this substitution?

‘Lysogenic’ literally means ‘Generating lysis’; see Lwoff (1953) for discussion of the early history of the study of lysogeny. The majority of phages, though, appear to be lysis generating. Indeed, that is precisely what should be meant by the term ‘Lytic phage’—a lytic phage literally is a lysis-generating phage. As a consequence, it logically can be preferable to state ‘Lytic and lysogenic’ rather than ‘Lytic or lysogenic’. The apparent equivalence of these two terms—terms that in ‘Lytic or lysogenic’ seemingly are used to imply polar opposites—stems from an error in usage. That is, rather than a description of a phage property, the term ‘Lysogenic’ when correctly employed is a description of a bacterial property. Specifically, certain bacterial cultures exist that when added to cultures of certain other bacterial strains can give rise to the lysis of these other cultures. The first culture thus has the property of being able to generate lysis in the second culture. This first culture therefore is lysis generating, that is, lysogenic (Lwoff 1953).

As scientific understanding has advanced, at least one of the conditions associated with this lysogenic property, that it can be a property of bacterial cultures, came to be associated with what today we refer to as lysogens: bacteria that harbor prophages. As part of this transition in meaning, note that Lwoff (1953), in his classic review, does not appear to even use ‘Lysogen’ but instead refers to a ‘Lysogenic bacterium’, as too does Adams (1959), though ‘Lysogen’ is found in Stent (1963). The term ‘Temperate phage’, by contrast, does appear in Lwoff as does also ‘Temperate’ alone, as in, “The temperate or virulent character of a phage” (p. 326).

Professionally Lytic or Temperate

With the phrase ‘Lytic or lysogenic’, as considered here, it is probable that virulent, obligately lytic, or strictly lytic is what generally is intended by ‘Lytic’, while ‘Temperate’ without question should replace ‘Lysogenic’. ‘Obligately lytic or temperate’ (four Google Scholar results), ‘Strictly lytic or temperate’ (two results), or instead ‘Virulent or temperate’ (136 results) therefore could be legitimate alternatives to ‘Lytic or lysogenic’. ‘Virulent’, though, and as noted, is burdened not only with historical ambiguity, but also may not be the most ideal of descriptors in terms of the marketing of virus-based medicinals. Indeed, within a phage therapy context, ‘Professionally lytic or temperate’ (zero results in either Google Scholar or Google Books) would seem to be the most meaningful alternative to the highly questionable, ‘Lytic or lysogenic’, that is, so long as ‘Professionally lytic’ phages contrast not just with temperate phages but with virulent derivatives of temperate phages as well (Table 2; Fig. 3). We suggest therefore that an effort might be made to replace even informal use of ‘Lytic or lysogenic’ with ‘Professionally lytic or temperate’, assuming, of course, that this is the distinction which is intended.

CONCLUSION

In this minireview, we have considered the diversity of phage types from the perspective of productive versus lysogenic infections along with lytic versus chronic release. We have emphasized issues associated with use of the terms ‘Lytic’ and ‘Lysogenic’ as stand-alone descriptors of phages and their properties, which either can be ambiguous (as is the case for ‘Lytic’) or etymologically inappropriate (for ‘Lysogenic’ as a descriptor of phages). In particular, we have criticized the phrasing, ‘Lytic or lysogenic’. We note as well that ‘Lysogenic’, logically, should never be used in association with non-lytic viral release from cells, that is, to describe phages that release their virions chronically or continuously from infected bacteria (category II). ‘Lysogenic’, strictly speaking, also is not an accurate general descriptor of all phage latent infections since ‘Lysogens’ associated with non-lytic viruses (category IV), such as the filamentous phage, CTXΦ (Mai-Prochnow et al.2015), are not lysis generating.

Despite our numerous concerns with use of the phrase, ‘Lytic or lysogenic’, there nonetheless exist circumstances in which the phrase unquestionably is valid. This is seen when describing the initial infection of a bacterium by a lytic, temperate phage (category III), such as phage λ, where the choice is between a lytic cycle or, instead, a lysogenic cycle, thus, ‘Lytic or lysogenic [cycles]’. The suitability of ‘Lytic or lysogenic’ as shorthand for distinguishing among phage ‘infection’ types—particularly lytic versus lysogenic ‘Cycles’ as one sees with phage λ—does not, however, imply an equivalent legitimacy of extension of this phrasing to distinguish among ‘Phage’ types.

STA has consulted and served on advisory boards for companies with phage therapy interests and maintains the websites phage.org and phage-therapy.org. ZH is an employee of EpiBiome Inc., a phage-based biotech company. Neither received help or financial support in writing the manuscript.

Conflict of interest. None declared.