Studies on lambda virulent mutants

The action of Type II restriction–modification (RM) systems depends on restriction endonuclease (REase), which cleaves foreign DNA at specific sites, and methyltransferase (MTase), which protects host genome from restriction by methylating the same sites. We here show that protection from phage infection increases as the copy number of plasmids carrying the Type II RM Esp1396I system is increased. However, since increased plasmid copy number leads to both increased absolute intracellular RM enzyme levels and to a decreased MTase/REase ratio, it is impossible to determine which factor determines resistance/susceptibility to infection. By controlled expression of individual Esp1396I MTase or REase genes in cells carrying the Esp1396I system, we show that a shift in the MTase to REase ratio caused by overproduction of MTase or REase leads, respectively, to decreased or increased protection from infection. Consistently, due to stochastic variation of MTase and REase amount in individual cells, bacterial cells that are productively infected by bacteriophage have significantly higher MTase to REase ratios than cells that ward off the infection. Our results suggest that cells with transiently increased MTase to REase ratio at the time of infection serve as entry points for unmodified phage DNA into protected bacterial populations.

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“…These genes are likely to be antibacterial as the disruption of transcription leads to cell cycle arrest [35]. These phages also possess other genes that are involved in counter-defensive activities against the host defense mechanisms, such as anti-restriction genes [36], host protease inhibitors [37], anti-repressor [38], and anti-crispr genes [39][40][41][42].…”

Section: Some Eskape Phages Have Genes With Antimicrobial Activitiesmentioning

confidence: 99%

A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models

Lee,

Hunter,

Shim

2024

Preprint

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Bacteriophages are the most prevalent biological entities in the biosphere. However, limitations in both medical relevance and sequencing technologies have led to a systematic underestimation of the genetic diversity within phages. This underrepresentation not only creates a significant gap in our understanding of phage roles across diverse biosystems but also introduces biases in computational models reliant on these data for training and testing. In this study, we focused on publicly available genomes of bacteriophages infecting high-priority ESKAPE pathogens to show the extent and impact of this underrepresentation. First, we demonstrate a stark underrepresentation of ESKAPE phage genomes within the public genome and protein databases. Next, a pangenome analysis of these ESKAPE phages reveals extensive sharing of core genes among phages infecting the same host. Furthermore, genome analyses and clustering highlight close nucleotide-level relationships among the ESKAPE phages, raising concerns about the limited diversity within current public databases. Lastly, we uncover a scarcity of unique lytic phages and phage proteins with antimicrobial activities against ESKAPE pathogens. This comprehensive analysis of the ESKAPE phages underscores the severity of underrepresentation and its potential implications. This lack of diversity in phage genomes may restrict the resurgence of phage therapy and cause biased outcomes in data-driven computational models due to incomplete and unbalanced biological datasets.

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“…These genes are likely to be antibacterial as the disruption of transcription leads to cell cycle arrest (Merrikh et al, 2023). These phages also possess other genes that are involved in counter-defensive activities against the host defense mechanisms, such as anti-restriction genes (Spoerel et al, 1979), host protease inhibitors (Meyn et al, 1977), anti-repressor (Horiuchi et al, 1974), and anti-crispr genes (Bondy-Denomy et al, 2012;Park et al, 2022a;Park et al, 2022b;Shim, 2022).…”

Section: Some Eskape Phages Have Genes With Antimicrobial Activitiesmentioning

confidence: 99%

A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models

Lee,

Hunter,

Shim

2024

Front. Mol. Biosci.

0

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Bacteriophages are the most prevalent biological entities in the biosphere. However, limitations in both medical relevance and sequencing technologies have led to a systematic underestimation of the genetic diversity within phages. This underrepresentation not only creates a significant gap in our understanding of phage roles across diverse biosystems but also introduces biases in computational models reliant on these data for training and testing. In this study, we focused on publicly available genomes of bacteriophages infecting high-priority ESKAPE pathogens to show the extent and impact of this underrepresentation. First, we demonstrate a stark underrepresentation of ESKAPE phage genomes within the public genome and protein databases. Next, a pangenome analysis of these ESKAPE phages reveals extensive sharing of core genes among phages infecting the same host. Furthermore, genome analyses and clustering highlight close nucleotide-level relationships among the ESKAPE phages, raising concerns about the limited diversity within current public databases. Lastly, we uncover a scarcity of unique lytic phages and phage proteins with antimicrobial activities against ESKAPE pathogens. This comprehensive analysis of the ESKAPE phages underscores the severity of underrepresentation and its potential implications. This lack of diversity in phage genomes may restrict the resurgence of phage therapy and cause biased outcomes in data-driven computational models due to incomplete and unbalanced biological datasets.

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Studies on lambda virulent mutants

Cited by 4 publications

References 19 publications

Cells with stochastically increased methyltransferase to restriction endonuclease ratio provide an entry for bacteriophage into protected cell population

Cells with stochastically increased methyltransferase to restriction endonuclease ratio provide an entry for bacteriophage into protected cell population

A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models

A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models

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