Diverse and abundant phages exploit conjugative plasmids

Quinones-Olvera, Natalia; Owen, Siân V.; McCully, Lucy M.; Mg, Marin; Rand, Elizabeth R.; Fan, Alice C; Dosumu, Oluremi J Martins; Paul, Kay; Castano, Cleotilde E. Sanchez; Paull, Jillian S.; Petherbridge, Rachel; Baym, Michael

doi:10.1101/2023.03.19.532758

Cited by 6 publications

(4 citation statements)

References 104 publications

(129 reference statements)

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“…Consequently, CRISPR-Cas may not always be essential but moderately beneficial for bacterial survival and therefore it could be located on a plasmid. Second, phages that depend on plasmids for infection are more abundant than previously thought [ 39 ]. These phages can only infect bacterial cells hosting a plasmid.…”

Section: Discussionmentioning

confidence: 99%

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My host’s enemy is my enemy: plasmids carrying CRISPR-Cas as a defence against phages

Siedentop,

Rüegg,

Bonhoeffer

et al. 2024

Proc. R. Soc. B.

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Bacteria are infected by mobile genetic elements like plasmids and virulent phages, and those infections significantly impact bacterial ecology and evolution. Recent discoveries reveal that some plasmids carry anti-phage immune systems like CRISPR-Cas, suggesting that plasmids may participate in the coevolutionary arms race between virulent phages and bacteria. Intuitively, this seems reasonable as virulent phages kill the plasmid’s obligate host. However, the efficiency of CRISPR-Cas systems carried by plasmids can be expected to be lower than those carried by the chromosome due to continuous segregation loss, creating susceptible cells for phage amplification. To evaluate the anti-phage protection efficiency of CRISPR-Cas on plasmids, we develop a stochastic model describing the dynamics of a virulent phage infection against which a conjugative plasmid defends using CRISPR-Cas. We show that CRISPR-Cas on plasmids provides robust protection, except in limited parameter sets. In these cases, high segregation loss favours phage outbreaks by generating a population of defenceless cells on which the phage can evolve and escape CRISPR-Cas immunity. We show that the phage’s ability to exploit segregation loss depends strongly on the evolvability of both CRISPR-Cas and the phage itself.

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Section: Discussionmentioning

confidence: 99%

“…R. Soc. B 291: 20232449 mobile genetic elements to estimate the consequences of their interactions for bacterial ecology and evolution, contributing to the recent attention in understanding the multi-party interactions between mobile genetic elements [6,10,[38][39][40].…”

Section: (B) Plasmid Segregation Loss Favours Phage Survival By Facil...mentioning

confidence: 99%

My host’s enemy is my enemy: plasmids carrying CRISPR-Cas as a defence against phages

Siedentop,

Rüegg,

Bonhoeffer

et al. 2024

Proc. R. Soc. B.

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“…Interestingly, a significant proportion of type IV CRISPR spacers match plasmid conjugation genes 7 , which are also involved in pilus formation. For example, phages using pili as receptors are widespread 53 , and it is possible that type IV-driven pili repression enhances plasmid fitness by preventing phage entry into host cells.…”

Section: Discussionmentioning

confidence: 99%

Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacersin trans

Benz,

Camara-Wilpert,

Russel

et al. 2023

Preprint

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Type IV-A CRISPR-Cas systems are primarily encoded on plasmids and form multi-subunit ribonucleoprotein complexes with unknown biological functions. In contrast to other CRISPR-Cas types, they lack the archetypical CRISPR acquisition module and encode a DinG helicase instead of a nuclease component. Type IV-A3 systems are carried by large conjugative plasmids that often harbor multiple antibiotic-resistance genes. Although their CRISPR array contents suggest a role in inter-plasmid conflicts, this function and the underlying mechanisms have remained unexplored. Here, we demonstrate that a plasmid-encoded type IV-A3 CRISPR-Cas system co-opts the type I-E adaptation machinery from its clinicalKlebsiella pneumoniaehost to update its CRISPR array. Furthermore, we demonstrate that robust interference of conjugative plasmids and phages is elicited through CRISPR RNA-dependent transcriptional repression. By targeting plasmid core functions, type IV-A3 can prevent the uptake of incoming plasmids, limit their horizontal transfer, and destabilize co-residing plasmids, altogether supporting type IV-A3's involvement in plasmid competition. Collectively, our findings shed light on the molecular mechanisms and ecological function of type IV-A3 systems and have broad implications for understanding and countering the spread of antibiotic resistance in clinically relevant strains.

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“…Even so, the knowledge of these phages is limited, although some recent studies have shown that some of them can have a great potential to be used to reduce ARGs’ load in microbial communities ( 22 – 24 ). Recently, He et al ( 25 ) and Quinones-Olvera et al ( 26 ) demonstrated that plasmid-dependent phages are in fact common and abundant in diverse environments.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of novel plasmid-dependent phages infecting bacteria carrying diverse conjugative plasmids

Parra,

Cockx,

Lutz

et al. 2024

Microbiol Spectr

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Plasmid-dependent phages infect bacteria carrying conjugative plasmids by recognizing the plasmid-encoded pilus. Despite the high abundance of conjugative plasmids in diverse environments, plasmid-dependent phages have not been widely studied. Since conjugative plasmids often carry antimicrobial resistance genes (ARGs), interfering with conjugation could reduce the spread of ARGs and avoid the appearance of multiresistant superbugs. Our aim was to isolate and characterize plasmid-dependent phages able to infect bacteria carrying diverse conjugative plasmids belonging to the most common plasmid families among Gram-negative pathogens. We isolated two lytic phages from wastewater using an avirulent strain of Salmonella enterica carrying the conjugative IncN plasmid pKM101. Both phages, named Lu221 and Hi226, are novel dsDNA viruses within the class Caudoviricetes with genomes of approximately 76 kb. They showed broad host range infecting Escherichia coli , S. enterica , Kluyvera sp., and Enterobacter sp. carrying conjugative plasmids. They recognize plasmid-encoded receptors from 12 out of 15 tested plasmids, all of them carrying resistance determinants. Phages Lu221 and Hi226 could have the potential to help combat the antimicrobial resistance crisis by reducing ARGs present in conjugative plasmids. IMPORTANCE This work was undertaken because plasmid-dependent phages can reduce the prevalence of conjugative plasmids and can be leveraged to prevent the acquisition and dissemination of ARGs by bacteria. The two novel phages described in this study, Lu221 and Hi226, can infect Escherichia coli , Salmonella enterica , Kluyvera sp. and Enterobacter sp. carrying conjugative plasmids. This was verified with plasmids carrying resistance determinants and belonging to the most common plasmid families among Gram-negative pathogens. Therefore, the newly isolated phages could have the potential to help control the spread of ARGs and thus help combat the antimicrobial resistance crisis.

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Diverse and abundant phages exploit conjugative plasmids

Cited by 6 publications

References 104 publications

My host’s enemy is my enemy: plasmids carrying CRISPR-Cas as a defence against phages

My host’s enemy is my enemy: plasmids carrying CRISPR-Cas as a defence against phages

Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacersin trans

Isolation and characterization of novel plasmid-dependent phages infecting bacteria carrying diverse conjugative plasmids

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