Accumulation of defense systems in phage-resistant strains of
            <i>Pseudomonas aeruginosa</i>

Costa, Ana Rita; van den Berg, Daan F.; Esser, Jelger Q.; Muralidharan, Aswin; van den Bossche, Halewijn; Bonilla, Boris Estrada; van der Steen, Baltus A.; Haagsma, Anna C.; Fluit, Ad C.; Nobrega, Franklin L.; Haas, Pieter-Jan; Brouns, Stan J. J.

doi:10.1126/sciadv.adj0341

Cited by 7 publications

(3 citation statements)

References 92 publications

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“…Our investigation into bacterial defense systems yielded unexpected results, as we found no evidence linking these systems to lytic phage susceptibility or resistance. Our findings are surprising given previous studies indicating the opposite, where defense mechanisms were shown to protect from phage infection 26,43,44 , or a recent study indicating an accumulation of defense systems in phage-resistant Pa strains 45 .…”

Section: Discussioncontrasting

confidence: 99%

“…Our experiments demonstrate that bacterial defense systems do not influence initial lytic phage infection, which determines host range. Different approaches or experiments exploring the relationship and evolution between phages and hosts over an extended period, particularly those focusing on the development of phage resistance, may yield different outcomes, shown by a recent study suggested an accumulation of defense systems in phage-resistant Pa strains 45.…”

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confidence: 99%

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Bacterial Receptors but Not Anti-Phage Defence Mechanisms Determine Host Range for a Pair ofPseudomonas aeruginosaLytic Phages

Müller,

Pourtois,

Kim

et al. 2024

Preprint

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As antimicrobial-resistant pathogens, particularly the rapidly mutating and adapting Pseudomonas aeruginosa, claim millions of lives worldwide each year, the development of novel therapeutic approaches becomes increasingly important. Bacteriophages (phages), viral predators of bacteria, represent a promising solution to fight bacterial infections. However, persistent challenges hinder the widespread application of phage therapy. One of these challenges is the narrow host range of bacteriophages, which are highly specific and only target a limited range of bacterial strains. This specificity poses difficulties in treating polymicrobial infections and limits broader application. Extensive research has been conducted to study host range, however, a definitive answer to the phage or bacterial factors determining phage host range remains elusive. In this work, we combined a transposon mutagenesis library and a Genome-Wide Association Study to identify bacterial genes associated with resistance or susceptibility to the lytic phages OMKO1 and LPS-5. We find that the flagellum is crucial for infection by phage OMKO1 and that lipopolysaccharide biosynthetic genes were significantly associated with LPS-5 phage susceptibility. These results suggest that these structures serve as receptors, which we confirmed through knockout swimming and LPS/O-antigen assays, respectively. Surprisingly, the presence of bacterial defense mechanisms was not a significant predictor of lytic phage infection but was for lysogenic phage infection. Together, these data indicate that receptor structures are important for phage infection. Conversely, they do not support existing paradigms regarding the central role of phage defense mechanisms in determining host range for lytic phages.

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 99%

Bacterial Receptors but Not Anti-Phage Defence Mechanisms Determine Host Range for a Pair ofPseudomonas aeruginosaLytic Phages

Müller,

Pourtois,

Kim

et al. 2024

Preprint

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“…No CRISPR-Cas or TA systems were identified in the analysis, only RM, AMP-ligating, and unidentified systems. Overall, the phage-defense system carriage rate of H. salinarum is low compared to bacteria, which can carry upwards of 15 defense systems [62].…”

Section: Discussionmentioning

confidence: 97%

In Silico Prophage Analysis of Halobacterium salinarum ATCC 33170

Peters,

Akache,

Chen

et al. 2024

Applied Microbiology

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The extremophile Halobacterium salinarum is an aerobic archaeon that has adapted to thrive in high-salt environments such as salted fish, hypersaline lakes, and salterns. Halophiles have garnered significant interest due to their unique interactions with bacteriophages known as haloarchaeophages. Studies have identified and characterized prophages in halophilic archaea, such as Haloferax volcanii, Haloquadratum walsbyi, and Haloarcula marismortui. Still, an investigation has yet to be conducted into the presence of prophage elements on Halobacterium salinarum ATCC 33170. This is of particular interest to us as we are using this strain as a source of archaeol, as one of the components of our sulfated lactosyl archaeol (SLA) archaeosome adjuvant. Genomic contigs of strain 33170 were bioinformatically assessed for prophage-like features using BLAST, PHASTER, InterProScan, and PHYRE2. A 7 kb region encoding six genes was identified as an incomplete prophage, and the proteins were further analyzed, revealing high homology to proteins encoded by bacteria, archaea, and an IS200 transposon. Restricting the BLASTp database to viruses resulted in hits to both myo- and siphoviral proteins, which would be unusual for an intact prophage. Additionally, no known phage structural proteins were identified in the search, suggesting a low chance that H. salinarum ATCC 33170 harbors a latent prophage.

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