Bacteria defend against phages through type IV pilus glycosylation

Harvey, Hanjeong; Bondy‐Denomy, Joseph; Marquis, Hélène; Sztanko, Kristina M.; Davidson, Alan R.; Burrows, Lori L.

doi:10.1101/150227

Cited by 2 publications

(2 citation statements)

References 50 publications

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“…It is known for several phages to bind lipopolysaccharides, specifically the Oantigen as their receptor. 34,35 LPS-5 is among the phages employed in the CF Bacteriophage Study at Yale. The researchers hypothesized that their isolated phage LPS-5 binds to lipopolysaccharide, however, the data supporting this hypothesis was not presented in the study.…”

Section: Lps-5 Exploits the O-antigen Of Lipopolysaccharide As A Rece...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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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: Lps-5 Exploits the O-antigen Of Lipopolysaccharide As A Rece...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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“…Mutations in genes encoding potential phage receptors such as pili proteins (23) and the outer membrane polysaccharides (LPS) (24) were found in both, phage-resistant and phage-sensitive clones suggesting a role in the adaptive response to phage attack. The mutations in various genes involved in these two biosynthetic pathways are shown in yellow for polysaccharides-synthesis related genes, and green for pili synthesis genes in fig.…”

Section: Gene Alterations With Potential Impact For Adaptation To Pha...mentioning

confidence: 99%

Diversification ofPseudomonas aeruginosabiofilm populations under repeated phage exposures decreases the efficacy of the treatment

Martinet,

Lohde,

Higazy

et al. 2024

Preprint

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Phage therapy has been proposed as a therapeutic alternative to antibiotics for treatment of chronic, biofilm-relatedP. aeruginosainfections. To get a deeper insight into the complex biofilm-phage interactions, we investigated in the present study the effect of three successive exposures to lytic phages of biofilms formed by the reference strains PAO1 and PA14 as well as of two sequential clinicalP. aeruginosaisolates from the sputum of a patient with cystic fibrosis (CF). The Calgary device was employed as biofilm model and the efficacy of phage treatment was evaluated by measurements of the biomass stained with crystal violet (CV) and of the cell density of the biofilm bacterial population (CFU/ml) after each of the three phage exposures. The genetic alterations ofP. aeruginosaisolates from biofilms exposed to phages were investigated by whole genome sequencing.We show here that the anti-biofilm efficacy of the phage treatment decreased rapidly with repeated applications of lytic phages onP. aeruginosastrains with different genetic background. Although we observed the maintenance of a small subpopulation of sensitive cells after repeated phage treatments, a fast recruitment of mechanisms involved in the persistence of biofilms to the phage attack occurred, mainly by mutations causing alterations of the phage receptors. However, mutations causing phage tolerant phenotypes such as alginate-hyperproducing mutants were also observed.In conclusion, a decreased anti-biofilm effect occurred after repeated exposure to lytic phages ofP. aeruginosabiofilms due to recruitment of different resistance and tolerance mechanisms.

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Bacteria defend against phages through type IV pilus glycosylation

Cited by 2 publications

References 50 publications

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

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

Diversification ofPseudomonas aeruginosabiofilm populations under repeated phage exposures decreases the efficacy of the treatment

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