Landscape of New Nuclease-Containing Antiphage Systems in Escherichia coli and the Counterdefense Roles of Bacteriophage T4 Genome Modifications

Wang, Shuangshuang; Sun, Erchao; Liu, Yuepeng; Yin, Baoqi; Zhang, Xueqi; Li, Mengling; Huang, Qi; Tan, Chen; Qian, Ping; Rao, Venigalla B.

doi:10.1128/jvi.00599-23

Cited by 10 publications

(3 citation statements)

References 43 publications

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“…Phage DNA modifications, such as 5ghmdC, impede the recognition and targeting of phage DNA by host nucleases and CRISPR-Cas systems 25 . The absence of these modifications would enhance phage DNA accessibility to host nucleases, resulting in phage genome degradation and the prevention of successful propagation 26,27 . No host-or phage-originating enzymes are currently known to specifically remove 5ghmdC modifications from the phage T4 genome.…”

Section: Resultsmentioning

confidence: 99%

Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications

Pozhydaieva,

Billau,

Wolfram-Schauerte

et al. 2024

Preprint

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Lytic bacteriophages hold substantial promise in medical and biotechnological applications. CRISPR-Cas systems offer a way to explore these mechanisms via site-specific phage mutagenesis. However, phages can resist Cas-mediated cleavage through extensive DNA modifications like cytosine glycosylation, hindering mutagenesis efficiency. Our study utilizes the eukaryotic enzyme NgTET to temporarily reduce phage DNA modifications, facilitating Cas nuclease cleavage and enhancing mutagenesis efficiency. This approach enables precise DNA targeting and seamless point mutation integration, exemplified by deactivating specific ADP-ribosyltransferases crucial for phage infection. Furthermore, by temporally removing DNA modifications, we elucidated the effects of these modifications on T4 phage infections without necessitating gene deletions. Our results present a strategy enabling the investigation of phage epigenome functions and streamlining the engineering of phages with cytosine DNA modifications. The described temporal modulation of the phage epigenome is valuable for synthetic biology and fundamental research to comprehend phage infection mechanisms through the generation of mutants.

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Section: Resultsmentioning

confidence: 99%

Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications

Pozhydaieva,

Billau,

Wolfram-Schauerte

et al. 2024

Preprint

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“…Bacteria and phages have also developed numerous other active measures to counter phage predation and subsequently counter the resultant antiphage defenses. In recent years, dozens of distinct antiphage systems have been identified and characterized [5][6][7][8][9][10][11][12][13][14][15][16][17], adding to long-known mechanisms that counter phage infection, such as restriction modification and CRISPR-Cas systems [18]. These systems can work synergistically, indicating the importance of a more comprehensive understanding of bacterial antiphage strategies and how they work together.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Pseudomonas aeruginosa Phage Resistance with the Numbers and Types of Antiphage Systems

Burke,

Urick,

Mzhavia

et al. 2024

IJMS

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Phage therapeutics offer a potentially powerful approach for combating multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using the web-server tool PADLOC (prokaryotic antiviral defense locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring resistance.

show abstract

“…Bacteria and phages have also developed numerous other active measures to counter phage predation and to subsequently counter resultant antiphage defenses. In recent years, dozens of distinct antiphage systems have been identified and characterized [5][6][7][8][9][10][11][12][13][14][15][16][17], adding to long-known mechanisms that counter phage infection such as restriction-modification and CRISPR-Cas systems [18]. These systems can work synergistically, indicating the importance of a more comprehensive understanding of bacterial antiphage strategies and how they work together.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Pseudomonas aeruginosa Phage Resistance with Numbers and Types of Antiphage Systems

Burke,

Urick,

Mzhavia

et al. 2023

Preprint

View full text Add to dashboard Cite

Phage therapeutics offer a potentially powerful approach to combat multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using web-server tool PADLOC (Prokaryotic Antiviral Defense Locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring the resistance.

show abstract

Landscape of New Nuclease-Containing Antiphage Systems in Escherichia coli and the Counterdefense Roles of Bacteriophage T4 Genome Modifications

Abstract: Cleavage of foreign DNA is a well-known mechanism used by bacteria to protect themselves from phage infections. Two well-known bacterial defense systems, R-M and CRISPR-Cas, both contain nucleases that cleave the phage genomes through specific mechanisms.

Cited by 10 publications

References 43 publications

Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications

Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications

Correlation of Pseudomonas aeruginosa Phage Resistance with the Numbers and Types of Antiphage Systems

Correlation of Pseudomonas aeruginosa Phage Resistance with Numbers and Types of Antiphage Systems

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