Bacteriophage-mediated spread of bacterial virulence genes

Penadés, José R.; Chen, John; Quiles-Puchalt, Nuria; Carpena, Núria; Novick, Richard P.

doi:10.1016/j.mib.2014.11.019

Cited by 289 publications

(212 citation statements)

References 51 publications

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“…Although bacteriophages have long been known to contribute to horizontal gene transfer (6), previous investigations have focused almost exclusively on certain phages’ capacity for transduction (8–10). Here we describe a distinct form of phage-mediated horizontal gene transfer, one characterized by the release of intact bacterial DNA upon lysis, and report the isolation and preliminary characterization of two novel Escherichia phages, SUSP1 and SUSP2, whose distinguishing transformation-promoting phenotype has not been previously described.…”

Section: Discussionmentioning

confidence: 99%

“…However, phages’ potential relevance for bacterial transformation has received considerably less attention, a fact underscored by several recent reviews’ exclusive focus on transduction in discussing phage-mediated gene transfer (8–10). Although phage infection and lysis are presumed to significantly enrich pools of extracellular DNA in natural environments (11), many fundamental questions, including the variability in different phages’ capacity to release intact host DNA, the distinguishing mechanism(s) associated with such release, and the transformability of phage-released host DNA, have not been investigated to date.…”

Section: Introductionmentioning

confidence: 99%

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Novel “Superspreader” Bacteriophages Promote Horizontal Gene Transfer by Transformation

Keen

Bliskovsky

Malagón

et al. 2017

mBio

115

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Bacteriophages infect an estimated 1023 to 1025 bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub “superspreaders,” releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation. Two novel Escherichia coli phage superspreaders, SUSP1 and SUSP2, liberated four evolutionarily distinct plasmids with equal efficiency, including two close relatives of prominent antibiotic resistance vectors in natural environments. SUSP2 also mediated the extensive lateral transfer of antibiotic resistance in unbiased communities of soil bacteria from Maryland and Wyoming. Furthermore, the addition of SUSP2 to cocultures of kanamycin-resistant E. coli and kanamycin-sensitive Bacillus sp. bacteria resulted in roughly 1,000-fold more kanamycin-resistant Bacillus sp. bacteria than arose in phage-free controls. Unlike many other lytic phages, neither SUSP1 nor SUSP2 encodes homologs to known hydrolytic endonucleases, suggesting a simple potential mechanism underlying the superspreading phenotype. Consistent with this model, the deletion of endonuclease IV and the nucleoid-disrupting protein ndd from coliphage T4, a phage known to extensively degrade chromosomal DNA, significantly increased its ability to promote plasmid transformation. Taken together, our results suggest that phage superspreaders may play key roles in microbial evolution and ecology but should be avoided in phage therapy and other medical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel “Superspreader” Bacteriophages Promote Horizontal Gene Transfer by Transformation

Keen

Bliskovsky

Malagón

et al. 2017

mBio

115

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“…However, the efficacy of CRISPR/Cas9 antimicrobials is still far from being therapeutic, mainly due to the low efficiency in phage-based delivery systems which limited the efficacy of CRISPR/Cas9 to reduce bacterial colony forming units (CFU) by only one or two logs in in vivo and in vitro assays1214. Furthermore, phage-based delivery systems may deliver not only a plasmid or phagemid harboring CRISPR/Cas system, but also host chromosomal segments by generalized and specialized transduction to target cells17. This is particularly important for phage-based delivery systems using S. aureus since many important staphylococcal virulence factors such as superantigens and cytolysins are commonly located in mobile genetic elements (MGEs) and are transferred to other S. aureus and Listeria monocytogenes by temperate phage-mediated generalized transduction1819, thereby raising the safety issues202122.…”

mentioning

confidence: 99%

Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus

Park

Moon

Park

et al. 2017

Sci Rep

126

115

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Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus.

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“…In fact, while much attention has been paid to conjugation, more recent work has additionally implicated bacteriophage as a major vehicle for horizontal gene transfer and recombination (7)(8)(9)(10).…”

mentioning

confidence: 99%

Abundance of Antibiotic Resistance Genes in Bacteriophage following Soil Fertilization with Dairy Manure or Municipal Biosolids, and Evidence for Potential Transduction

Ross

Topp

2015

Appl Environ Microbiol

103

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Animal manures and municipal biosolids recycled onto crop production land carry antibiotic-resistant bacteria that can influence the antibiotic resistome of agricultural soils, but little is known about the contribution of bacteriophage to the dissemination of antibiotic resistance genes (ARGs) in this context. In this work, we quantified a set of ARGs in the bacterial and bacteriophage fractions of agricultural soil by quantitative PCR. All tested ARGs were present in both the bacterial and phage fractions. We demonstrate that fertilization of soil with dairy manure or human biosolids increases ARG abundance in the bacterial fraction but not the bacteriophage fraction and further show that pretreatment of dairy manure can impact ARG abundance in the bacterial fraction. Finally, we show that purified bacteriophage can confer increased antibiotic resistance to soil bacteria when combined with selective pressure. The results indicate that soilborne bacteriophage represents a substantial reservoir of antibiotic resistance and that bacteriophage could play a significant role in the horizontal transfer of resistance genes in the context of an agricultural soil microbiome. Overall, our work reinforces the advisability of composting or digesting fecal material prior to field application and suggests that application of some antibiotics at subclinical concentrations can promote bacteriophage-mediated horizontal transfer of ARGs in agricultural soil microbiomes. Overuse of antibiotics has contributed to the spread of antibiotic resistance due to the release of antibiotics, antibioticresistant bacteria, and antibiotic resistance genes (ARGs) into the environment (1). This phenomenon is mediated by horizontal gene transfer (HGT) of mobile genetic elements-such as plasmids, transposons, and integrons-between bacterial cells through conjugation and viral transduction (2-4).Transduction has been shown to occur in environmental matrices, including freshwater and wastewater; moreover, bacterial 16S ribosomal RNA sequences have been observed in the viral fraction of wastewater, confirming the ability of bacteriophage to carry bacterial genes (5, 6). In fact, while much attention has been paid to conjugation, more recent work has additionally implicated bacteriophage as a major vehicle for horizontal gene transfer and recombination (7-10).Using high-throughput sequencing of murine fecal phage populations, Modi et al. (11) demonstrated that antibiotic treatment leads to the enrichment of genes conferring resistance to the administered drug as well as to unrelated antibiotics in the phage genome. Furthermore, bacteriophage from drug-treated mice provided cultured naive microbiota with increased levels of resistance to the corresponding drug. Overall, this work concluded that antibiotic residues potentiate the transduction-mediated dissemination of ARGs.Antibiotic resistance genes have been found in the bacteriophage DNA fraction of various environmental matrices, such as activated sludge (12), urban sewage and river water (13), an...

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Bacteriophage-mediated spread of bacterial virulence genes

Cited by 289 publications

References 51 publications

Novel “Superspreader” Bacteriophages Promote Horizontal Gene Transfer by Transformation

Novel “Superspreader” Bacteriophages Promote Horizontal Gene Transfer by Transformation

Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus

Abundance of Antibiotic Resistance Genes in Bacteriophage following Soil Fertilization with Dairy Manure or Municipal Biosolids, and Evidence for Potential Transduction

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