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Muniesa, M.; Rodriguez-Rubio, L.; Schwidder, M.; Schmidt, H. Shiga Toxin-Producing Escherichia coli. Encyclopedia. Available online: https://encyclopedia.pub/entry/8597 (accessed on 06 December 2025).
Muniesa M, Rodriguez-Rubio L, Schwidder M, Schmidt H. Shiga Toxin-Producing Escherichia coli. Encyclopedia. Available at: https://encyclopedia.pub/entry/8597. Accessed December 06, 2025.
Muniesa, Maite, Lorena Rodriguez-Rubio, Maike Schwidder, Herbert Schmidt. "Shiga Toxin-Producing Escherichia coli" Encyclopedia, https://encyclopedia.pub/entry/8597 (accessed December 06, 2025).
Muniesa, M., Rodriguez-Rubio, L., Schwidder, M., & Schmidt, H. (2021, April 12). Shiga Toxin-Producing Escherichia coli. In Encyclopedia. https://encyclopedia.pub/entry/8597
Muniesa, Maite, et al. "Shiga Toxin-Producing Escherichia coli." Encyclopedia. Web. 12 April, 2021.
Shiga Toxin-Producing Escherichia coli
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This entry is adapted from the peer-reviewed paper 10.3390/pathogens10040404

Shiga toxins (Stx) of Shiga toxin-producing Escherichia coli (STEC) are generally encoded in the genome of lambdoid bacteriophages, which spend the most time of their life cycle integrated as prophages in specific sites of the bacterial chromosome. Upon spontaneous induction or induction by chemical or physical stimuli, the stx genes are co-transcribed together with the late phase genes of the prophages. After being assembled in the cytoplasm, and after host cell lysis, mature bacteriophage particles are released into the environment, together with Stx. As members of the group of lambdoid phages, Stx phages share many genetic features with the archetypical temperate phage Lambda, but are heterogeneous in their DNA sequences due to frequent recombination events. In addition to Stx phages, the genome of pathogenic STEC bacteria may contain numerous prophages, which are either cryptic or functional. These prophages may carry foreign genes, some of them related to virulence, besides those necessary for the phage life cycle.

Stx phages STEC Lysogeny transduction HUS Escherichia coli Shiga toxin lambdoid prophages

1. Introduction

Soon after the first reported outbreak with pathogenic Shiga toxin-producing E. coli (STEC) O157:H7 (syn. enterohemorrhagic E. coli (EHEC)) in Oregon and Michigan, USA, in 1983, the ability of these pathogens to produce Stx (syn. Shiga-like toxin, verocytotoxin, verotoxin) was demonstrated to be encoded by bacteriophages [1]. Following this observation, Alison O’Brien’s group genetically and morphologically characterized two Stx converting phages induced from E. coli O26 and E. coli O157:H7 strains [2]. Phages H19J and 933J showed a typical head-tail structure with short tails. Some years later, Huang et al. demonstrated the homology of Stx1-converting bacteriophage H19-B to phage lambda by southern blot hybridization and restriction analysis [3]. During the following years, methodological developments allowed for an accurate characterization of Stx phages, making it clear that these phages comprise a family of genetically heterogeneous members [4][5][6][7][8][9]. Whole genome sequencing yielded the sequence data of hundreds of pathogenic STEC genomes in the National Center for Biotechnology Information (NCBI) database (https://www.ncbi.nlm.nih.gov/genome/browse#!/prokaryotes/167/, accessed on 26 March 2021), which confirmed the heterogeneity of Stx phage genomes. These differences, in turn, influence the bacterial genome structure and its functionality [10]. Furthermore, the prophage sequences demonstrate that all Stx phages conserve a basic lambdoid structure that is discussed below.

2. Morphology, Genetic Structure and Integration Sites of Stx Phages

All known Stx phages are double-stranded DNA-phages with a functional genetic organization similar to that of the archetypical phage lambda, which is one of the best studied E. coli phages [11][12]. Stx phages share a common head-tail structure ranging from icosahedral or elongated heads to contractile, non-contractile, or short tails with or without tail fibers [9][13][14][15][16][17][18][19].

Although all Stx phages share the same lambda-like genetic structure, significant variations in their genetic composition occur and genome sizes ranging from 28.7 to 71.9 kb have been described [17][20][21][22].

According to their morphological structure, Stx phages are classified into different families of the order Caudovirales. For example, the Stx2a phage 933W of the E. coli O157:H7 strain EDL933 consists of a short tail and regular hexagonal head and belongs to the Podoviridae family [18], whereas the prototype Stx1 phage H19-B [3][15] consists of an elongated head with a long non-contractile tail compatible with phages of the Siphoviridae family. While most of the characterized Stx2 phages belong to the family Podoviridae [9][23][24], only a few reports exist where Stx phages have been described as members of the family Myoviridae [25].

A large majority of short-tailed Stx phages (among them the Stx2 phages 933W and Sp5 of E. coli O157 strains EDL933 and Sakai) use highly conserved tail spike proteins for host recognition [23]. Sequence homologues of the tail spike protein gene of short-tailed Stx phages were also found in the genomes of Stx phages of the Siphoviridae and Myoviridae family [26]. Essential for phage adsorption is the highly conserved receptor protein YaeT (also known as BamA) on the bacterial cell surface and its orthologues, which ensure the spread among various members of the family of Enterobacteriaceae [23][27]. Two other potential receptor proteins, FadL and LamB, have been described for phages Stx2Φ-I and Stx2Φ-II, isolated from clinical STEC strains [28], but they could not be confirmed in later studies as functional receptors for phage Sp5 of the E. coli O157 strain Sakai [27].

As lambdoid phages, Stx phages share a general genetic structure with immediate early, delayed early, and late phase genes. All of them possess a common regulatory system that includes different variants of cro, cI, N, and Q genes, which are involved in the regulation of the phage entering the lysogenic or lytic life cycle [19][20][29][30]. All Stx phages known so far show a conserved location of the stx genes in the late regulatory region of the prophage genomes (Figure 1) [8][11][19][31][32]. More precisely, stx genes are located downstream of the gene encoding the antiterminator protein Q and upstream of the lysis cassette consisting of S, R, and Rz, and are thereby under control of the late promoter pR’ [7][8][18][19][33] (Figure 1). However, the genomic region between the antiterminator Q gene and stx has been shown to be diverse among Stx phages of the same subtype, and is therefore supposed to have an influence on the Stx expression level [34]. Variations of the Q gene have also been reported, which are thought to have a minor impact on Stx expression and correlate loosely with a clinical or bovine origin of the strains [35]. It is hypothesized that Q21 genes similar to the one of φ21 are often associated with lower Stx expression than the Q933 gene variants of phage 933W [36][37]. Nevertheless, these results are not completely clear and could not be supported by other studies [38]. Most probably, there are various unidentified factors also contributing to the level of Stx expression [35][38].

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Figure 1. Regulation scheme of stx expression in bacteriophage 933W of E. coli O157:H7 strain EDL 933 comprising relevant genes (colored in orange) and regulatory elements (not to scale), modified from Wagner and Waldor 2002 [30]. During the lysogenic state (indicated in grey arrows), transcription is inhibited through binding of the cI-encoded repressor protein to operator sites of the early promoters pL and pR (colored in grey); transcription is also terminated by downstream terminators (dark blue). Upon phage induction, autocleavage of the cI-encoded repressor protein allows transcription at pL, resulting in the production of phage-encoded antiterminator protein N (red), which enables polymerase read-through at downstream terminators including tL1 and tR1. This, in turn, leads to the expression of the late-phase antiterminator Q (red), which facilitates transcription initiating at the late-phase promoter pR’, transcending terminator tR’, and resulting in the expression of downstream genes including stx (indicated in light blue arrows). Additionally, the expression of O- and P-encoded phage replication products leads to increased Stx production by amplifying stx copy numbers [30][39].

Genomic differences have also been reported for the early regulatory regions of Stx phages. For example, Stx2 phage 933W contains three operator sites in the right operator region, but only two operator sites in the left operator region, which is different from phage lambda and most other lambdoid phages [39]. In contrast, Stx1 phage H-19B contains four operator sites in the right operator region [40]. It is not well understood how these differences in the early regulatory region affect repressor/operator interactions and, thereby, expression of Stx. However, it was demonstrated that spontaneous induction occurs more readily in Stx phages than in lambdoid prophages without stx genes [39][41].

During the lysogenic state, transcription of most phage genes is mostly silenced by the CI repressor binding at the operators within the early regulatory region [42]. Although expression of certain Stx phage genes during the lysogenic state has been reported [43], it was attributed to a small subset of cells that spontaneously induced the lytic cycle. Thereby, the transcription of phage genes is terminated at tR’ located directly downstream of pR’, thus preventing the transcription of stx genes. Upon phage induction, a cascade of regulatory events leads to the expression of early and late antiterminator proteins N and Q, respectively, allowing polymerase read-through of downstream terminators [30] (Figure 1).

Interestingly, a continuous transcription activity at phage late promoter pR’, which is terminated directly downstream at tR’, generates a short RNA byproduct under lysogenic conditions [44]. It was demonstrated that this regulatory small RNA represses expression of Stx1 under lysogenic conditions and modulates host fitness [45].

Stx phages can harbor a number of additional genes acquired by horizontal gene transfer [9][20]. These so-called morons (“more-on” refers to additional DNA on the phage genomes) are mainly found in the late phage region and usually have a different nucleotide composition compared to the rest of the phage genome. Furthermore, morons may have their own promoter and terminator sequences, so the transcription is independent from phage induction. These genes have no obvious function for the phage but are typically beneficial for the host [9][46].

The STEC genome can contain various Stx prophages and diverse non-Stx prophages [47]. Several strains naturally carry more than one Stx phage and double, or even triple, lysogens of the same Stx phage can be experimentally produced [48][49]. Stx phage integrases seem to have evolved to recognize different insertion sites within the bacterial chromosome. Thus, although each Stx phage integrates preferentially in one particular site, the integrase is able to recognize secondary sites for the phage genome integration if this preferred site is occupied or deleted [50].

Several chromosomal insertion sites have been described for Stx phages: yehV encoding a regulator for curli expression [51][52], wrbA encoding the Trp repressor-binding protein [18], yecE whose function is unknown [32], sbcB encoding an exonuclease [17][53], Z2577 encoding an oxidoreductase [54], ssrA encoding a tmRNA [55], prfC encoding a peptide chain release factor [56], argW encoding a tRNA [57], and the intergenic region between torS and torT genes [56]. In addition, a study by Steyert et al. revealed five novel insertion sites (potC, yciD, ynfH, serU, yjbM) in Locus of Enterocyte Effacement (LEE)-negative STEC isolates that had not been reported to be occupied by Stx phages before [58]. Several new insertion sites have been described for Stx phages carrying the novel Stx2 subtypes Stx2h and Stx2k [21][59]. The Stx2k prophage was found to be integrated adjacent to the yjjG, encoding a nucleotide phosphatase [59][60]. Different insertion sites were described for the Stx2k phages including dusA, which encodes a tRNA dihydroxyuridine synthase A [61], yccA, a predicted transmembrane protein [62][63], and the zur gene encoding a zinc uptake regulator [21][64].

Unlike phage lambda, Stx phages can occur as multiple isogenic prophages in the bacterial chromosome at different insertion sites [50][65]. Whereas phage lambda leads to host immunity, Stx phages are able to evade superinfection immunity [48][49][66]. For example, Stx2 phage Φ24B was shown to integrate into a single host at least three times and furthermore, it was demonstrated that the frequency of multiple lysogens increased with each integrated prophage [9][67]. Different results were reported concerning the influence of multiple lysogens on the toxin expression level: interestingly, experiments with a double isogenic Stx2 phage showed an enhanced production level of Stx [65], whereas other studies with two different Stx2 prophages showed reduced toxin levels [48][68].

3. Induction, Expression and Release of Stx

When Stx phages choose the lysogenic pathway, phage DNA is inserted into the E. coli chromosome, forming a prophage that is replicated together with the bacterial chromosome, transferred to the bacterial progeny by vertical gene transfer and maintained for many cell generations. When diverse environmental conditions threaten the viability of the bacterial cell, these stimuli trigger the SOS response, activating the induction of the prophage. Several of these stimuli have been identified including changes in pH, particularly low pH [69], presence of iron [70], presence (or absence) of ions, which also confers a role on chelating agents such as EDTA and sodium citrate [71][72], several antibiotics including growth promoters [73][74], and other agents causing DNA damage such as mitomycin C or hydrogen peroxide [75][76][77].

After induction, prophages are excised from the chromosome. The viral DNA, which exists as a separate molecule within the bacterial cell, then replicates separately from the host bacterial DNA as an extrachromosomal element [78]. It has been found that stx can be detected in a circular, extrachromosomal state when the non-chromosomal elements are analyzed by southern blot after a PFGE of S1-digested DNA from STEC strains [79]. Moreover, circularized plasmid-like pseudolysogens of Stx phages have been observed in studies of integration of Stx phage Φ24B [67]. Plasmids derived from Stx phages have also been used to study the efficiency of DNA replication of lambdoid phages [78].

During replication, expression of the phage structural proteins and Stx takes place. The structural components are assembled into new Stx phage particles, which are released from the cell by the action of phage lytic proteins expressed at the end of the induction process. These proteins cause the disruption of the bacterial host cell, allowing the release and spread of Stx [8][42], which is the main virulence factor determining the severity and lethality of the STEC infection [80].

Stx can also be released by outer membrane vesicles (OMV) [81][82][83][84]. These OMVs protect Stx and other proteins from degradation by proteases and mask its presence in cytotoxicity or bead-enzyme-linked immunosorbent assays [81]. It was shown that OMVs from the hypervirulent O104:H4 outbreak strain are also internalized by intestinal epithelial cells despite not expressing the typical GB3 receptor [84]. A major study by Bielaszewska et al. also described this internalization strategy. Briefly, vesicles were taken up via dynamin-dependent endocytosis, followed by retrograde transport of the Stx holotoxin in early endosomes toward the Golgi complex and endoplasmatic reticulum. The enzymatic active Stx2A subunit could then be transported to the cytosol and bind to the ribosome [83].

In addition to Stx release, the new Stx phages are set free, which allows the dissemination and acquisition of the stx gene among susceptible cells (E. coli or even other genera) present in the same biome [85], contributing to the evolution of STEC [86]. In this context, stx genes have been detected in Citrobacter freundii [87], Enterobacter cloacae [88], Shigella sonnei [89], and Aeromonas spp. [90].

The effective production of Stx2 is always dependent on phage induction, whereas Stx release is dependent on cell lysis [42]. However, a different situation can be observed for Stx1, encoded by Stx1 phages [58][70][91]. The expression of Stx1 is caused by two independent promoters. The first is a late phage promoter pR’ dependent on phage induction (as for Stx2 phages), which allows the expression and release of the toxin by the phage-mediated cell lysis. The second is a specific Stx1 promoter containing a binding site for Fur protein, which makes complexes with iron. Thus, in the presence of iron, Fur blocks Stx1 expression, while in the absence of iron, this repression does not occur and Stx1 is expressed. This situation is entirely independent of phage induction, and Stx1 levels of production are similar to those observed under conditions where the Stx1 phage is not induced [70]. The main consequence of the phage-independent expression of Stx1 is that cells expressing Stx1 can avoid cell lysis, enhancing their survival. Fewer strains producing Stx1 phages means a lower occurrence of free Stx1 phages compared with Stx2 phages, which has been confirmed by analyzing free Stx1 vs. Stx2 phages in extracellular biomes [91].

In any case, Stx2 or Stx1 phage induction poses a serious threat for the survival of the STEC population, which must sacrifice its prevalence for the sake of increasing its virulence. The solution of the paradox presented by Stx as a virulence factor that forces phage activation and cell lysis in order to be expressed and released, is obtained when considering the heterogeneity of the STEC population. In a bacterial population, not all bacterial cells behave synchronously since they are not in the same physiological or growth state, therefore not all of them activate phage induction simultaneously. Thus, one subpopulation will induce Stx phages, producing new virions and expressing the toxin, while another subpopulation remains in the lysogenic state, enhancing its survival and becoming the population’s reservoir [92]. Although the mechanism dealing with the differences between the inducible and the non-inducible stage have not yet been completely elucidated, the growth state seems to play a role. Cells reaching the stationary phase prevent induction better than cells in the exponential phase. The RpoS factor, highly expressed in E. coli cells in the stationary phase, was shown to cause a dramatic delay in Stx phage induction within the E. coli population, and overexpression of RpoS resulted in a large number of E. coli cells that do not induce the Stx prophage [92]. In contrast, in E. coli, lambda prophage induction has been shown to be regulated by the OxyR protein [93].

The differential induction of Stx phages within the STEC population is indeed considered an altruistic strategy shown by a fraction of the STEC cells, rendering the expression of Stx a positive force for the benefit of the whole population [94]. It has been seen in cells spontaneously inducing Stx phages [41] under natural conditions but also in the presence of H2O2, which is produced by neutrophiles during STEC infection in the human body [94].

4. Stx Phages as Pathogenic Principle

In addition to stx, many additional genes have been described in Stx prophage genomes, which may contribute to pathogenicity and virulence, but also to the competitiveness with other gut bacteria in the human host. There are a number of reviews and book chapters that have described the role of some genes in the Stx phages that contribute to regulating pathogenicity in STEC [9][10][46][71][95], and therefore, their structure, function, and roles in pathogenicity will not be reviewed here.

However, there is one newer gene family that is worth describing, since it is present in a number of Stx and non-Stx phages of pathogenic STEC. In preliminary work, an open reading frame (ORF) located downstream of the stx operon in the genome of phage 933W of E. coli O157:H7 and other relevant STEC serotypes was identified [96]. This ORF (z1466) could be induced in microarray experiments together with stx upon norfloxacin treatment of E. coli O157:H7 strain EDL933 [97]. When cultured in simulated colonic environmental medium (SCEM), a 40-fold expression of the corresponding protein P42 was observed [98]. Comparative analyses showed that the gene z1466 is highly homologous to a Neu5,9Ac2-esterase gene from E. coli that has already been in the focus of several studies [99][100]. By molecular and biochemical analyses, it was shown that z1466 indeed encodes a Neu5,9Ac2-acetylesterase, with an active esterase function similar to the chromosomally-encoded NanS, present in many E. coli strains [101]. Moreover, the gene was significantly longer than nanS and contained regions without homology to any known genes [102]. The function of the esterase as well as the role of seven vs. 10 Neu5,9Ac2 acetylesterases (NanS-p) from E. coli O157:H7 strain EDL933, and of five NanS-ps from E. coli O104:H4 strains C227-11φcu were analyzed, and it was shown that all these enzymes were encoded in prophage genomes that produced active esterases from their corresponding nanS-p alleles [101][103]. These results were in concordance with Eric Vimr’s early work [99] showing that cleavage of the O-acetyl residues from Neu5,9Ac2 allowed the lysogen to grow with Neu5,9Ac2 as a single carbon source. Furthermore, experiments with bovine maxillary gland mucin revealed the cleavage of mono, di, and triacetylated O-glycans by the NanS-p enzymes [102]. Similar experiments with the 2011 outbreak strain O104:H4 C227-11φcu revealed comparable results [103]. Taken together, the experiments have shown that these phage-encoded NanS-p enzymes can be used by pathogenic STEC strains to utilize mucin components for their growth, conferring an advantage to the lysogens [100][102][103][104] (Figure 2).

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Figure 2. Scheme of putative functions of the phage-encoded O-acetyl esterase in the large intestine. Pathogenic STEC cells have to traverse the loose and the tight mucus layer to reach the epithelium for adherence and colonization. Mucinases and other proteases play a role in that process. Cleavage of O-acteyl residues from terminal O-glycans (e.g., Neu5,9Ac2) by chromosomal and phage-encoded O-acetyl esterases results in deacetylated free sialic acids such as N-acetyl neuraminic acid, which can be metabolized by the bacteria [105]. The chemical structure of Neu5,9Ac2 is shown. Honeycomb structure = mucin network. Paneth cells and goblet cells are indicated.

The fact that nanS-p genes are generally located in phage genomes and that Neu5,9-O-acteylesterases are able to cleave O-acetyl residues from sugar moieties [106] raises the question whether this enzyme may play a role in the phage replication cycle itself and consequently could contribute to the STEC infection process. A very interesting aspect of the NanS-p function came from the structural annotation by homology modeling of the esterase domain and crystal structure analysis of the C-terminal domain of the conserved carbohydrate esterase vb_24B_21 from the Stx phage φ24B, which is homologous to nanS-p [104]. The authors proposed a lectin-like, jelly-roll sandwich-fold in the C-terminus with a proposed function in carbohydrate-binding for this domain [104]. It was hypothesized that such a structure could target the enzyme to its substrate to increase the local concentration and to improve catalysis, as shown for similar enzymes [107][108]. Up to now, there is no experimental evidence that this is the case for NanS-ps of pathogenic E. coli. However, carbohydrate-binding may be advantageous for pathogenic E. coli, which can use mucins with a particular carbohydrate structure as the substrate.

Another possibility is that NanS-ps could also be an advantage for the phages itself by enhancing the recognition of phage receptors at the bacterial outer membrane surface. In Gram-negative bacteria, phages have to encounter the LPS, which may function as an initial binding site for infection [109][110][111]. O-antigens of the lipopolysaccharide may be acetylated, and cleavage of these O-acetyl groups may facilitate phage binding [110][112] as well as subsequent traversing of the LPS to reach the specific receptor sites located at the outer membrane [113]. Whether NanS-ps may play a role for the attachment of Stx phages remains to be elucidated.

5. New Stx Phages

Aside from the two main immunologically distinct toxin types Stx1 and Stx2 [114], several subtypes have been described according to the nomenclature proposed by Scheutz et al. [115]. Whereas Stx1 presents the more homogeneous group consisting of subtypes Stx1a, Stx1c, and Stx1d, the Stx2 group is more heterogeneous and also more frequently associated with severe forms of diseases such as hemorrhagic colitis or HUS [116][117]. Additionally, the level of Stx expression has been shown to be correlated with different Stx subtypes and phages [118]. In a study by Fitzgerald et al., using an E. coli O157 strain harboring both Stx2a and Stx2c phages, it was demonstrated that Stx2a was induced more rapidly and to higher levels than Stx2c [119]. Whereas Stx2c phages seem to be highly homogeneous, as reported by Ogura et al., during a comprehensive analysis of Stx2 phages in 123 EHEC O157 strains, Stx2a phages could further be subtyped according to their replication proteins. The respective Stx2a subtypes also correlated with the level of Stx2a expression in the host strains [68].

In addition to the well-known subtypes Stx2a, Stx2b, Stx2c, Stx2d, Stx2e, Stx2f, and Stx2g, several phages harboring new stx subtypes were described. For example, the novel Stx2 subtype h, which was found in STEC strains isolated from intestinal tracts of healthy marmots in China. The Stx2h prophage was reported to be 49,713 bp in size [59]. Sequence analysis revealed 93 predicted coding sequences (CDSs), out of which 37 were hypothetical proteins or mobile elements with unknown function, while phage-specific genes, encoding proteins responsible for integration, transcriptional regulation, and lysis, were found in accordance to other Stx2 phages [59].

A further Stx2 subtype, Stx2i, was described in STEC isolates recovered from shrimps and bivalves, but no further information concerning the genomic characteristics of the respective phages was given [120][121]. The same applies to the subtype Stx2j, which was mentioned in a publication by Yang et al., but without further information [21]. The latest subtype described so far, Stx2k, was identified in E. coli strains isolated from different sources in China including humans, animals, and raw meat [21]. Interestingly, the isolated E. coli strains, which carried the Stx2k phage, showed considerable heterogeneity in serotype, genome sequence, and virulence gene profile. One of the analyzed STEC strains even harbored the plasmid-encoded heat-stable enterotoxin gene sta as well as two copies of enterotoxin gene stb, which were located on the chromosome. As the presence of these enterotoxins is characteristic for enterotoxigenic E. coli (ETEC), they reveal an STEC/ETEC hybrid pathotype and point out the contribution of phages to the rise of new virulent bacteria. Similar results were found for the Stx2k-converting phages of these strains as they also showed considerable heterogeneity concerning insertion sites, genetic content, and structure as well as in stx expression level and cytotoxicity. The phage genome sizes ranged from 28,694 bp to 54,005 bp, with predicted CDSs between 53 and 86.

6. Structure and Function of Non-Stx Phages of Pathogenic STEC

Aside from Stx phages, other non-Stx prophages are found in the genome of STEC, some of them including complete and inducible phages, but also non-inducible, remnant, cryptic, or residual phages. Polylysogeny is therefore a very common occurrence in STEC strains, and a good example is O157 strain Sakai, which carries up to 18 different prophages [13]. As temperate phages, prophages preferentially belong to the Siphoviridae or Podoviridae morphological types [122] and usually display a modular structure, the so-called genetic mosaicism [123]. Similar sequences are also shared by different phages. For this reason, it is difficult to distinguish between Stx and non-Stx phages in the STEC complete genomes because these similar sequences confound the software used for contigs assembly, producing false chimeras. This problem is overcome when using sequencing platforms that generate longer reads [47], or by inducing and isolating the prophages before sequencing [10].

Nevertheless, the abundance of prophages in STEC strains suggests some advantage for the actors implicated, that is, bacteria and phages. Bacteria seem to keep all this prophage pool to incorporate new genetic traits [124], but also to enhance the mobilization of their genome [13][125] or, as mentioned in the previous section, confer fitness and improve growth, or regulate other elements.

Prophages coexisting in a bacterial genome also take advantage of polylysogeny, increasing their genetic diversity. Multiple recombination events between prophages located in the same genome might occur [16][124], mainly between the identical fragments of DNA shared by the co-existing prophages. These shared sequences serve to anchor the activity of recombinases, which in many cases are encoded by the prophage genomes themselves [126] or that can be provided by the host. For example, new Stx1 phages are generated after recombination events occurring between the Stx1 and Stx2 prophages [13].

Other genetic elements can interact with prophages, for example, by taking their capsids to mobilize themselves; in E. coli, this fact has been described for genomic islands [127], defective prophages [14][128][129], and plasmids [130].

8. Final Remarks

The study of Stx phages in the field of pathogenic STEC has contributed to understand that phages play a pivotal role on the virulence mechanisms of this pathogen. Moreover the study of Stx phages can serve as a model to better understand the contribution of phages to bacterial physiology and metabolism and finally, to the development of human diseases.

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Subjects: Microbiology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Maite Muniesa , Lorena Rodriguez-Rubio , Maike Schwidder , Herbert Schmidt
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