Structure of Pyocin R

Yui, Chie

doi:10.1093/oxfordjournals.jbchem.a129437

Cited by 14 publications

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“…R-pyocin subtype and specificity are conferred by differences in the "foot" of the tail fiber (Fig. 1), which is believed to bind to specific residues on the lipopolysaccharide (LPS) decorating the outer membrane of Gram-negative bacteria (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). A strain may be susceptible or resistant to any variation of the different R-types (2,3,14,25,(27)(28)(29).…”

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confidence: 99%

Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs

Mei

Thomas

Diggle

2021

mBio

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Bacteriocins are proteinaceous antimicrobials produced by bacteria that are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Pseudomonas aeruginosa. Due to their antipseudomonal activity, R-pyocins have potential as therapeutics in infection. P. aeruginosa is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF). P. aeruginosa organisms from CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential. P. aeruginosa populations become phenotypically and genotypically diverse during infection; however, little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1 to R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screened P. aeruginosa strains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources, (ii) a large number of strains lack R-pyocin genes, and (iii) isolates collected from the same patient have the same R-type. We then assessed the impact of intrastrain diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage. IMPORTANCE R-pyocins have potential as alternative therapeutics against Pseudomonas aeruginosa in chronic infection; however, little is known about the efficacy of R-pyocins in heterogeneous bacterial populations. P. aeruginosa is known to become resistant to multiple antibiotics and to evolve phenotypic and genotypic diversity over time; thus, it is particularly difficult to eradicate in chronic cystic fibrosis (CF) lung infections. In this study, we found that P. aeruginosa populations from CF lungs maintain the same R-pyocin genotype but exhibit heterogeneity in susceptibility to R-pyocins from other strains. Our findings suggest there is heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, highlighting the necessity of further studying the potential of LPS-binding antimicrobial particles as alternative therapies in chronic infections.

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confidence: 99%

Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs

Mei

Thomas

Diggle

2021

mBio

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“…The proposed mode of action involves the R-pyocin tail fiber foot binding to a monosaccharide receptor on the lipopolysaccharide (LPS) (specific to each R-subtype), causing the sheath to contract and push the tail spike and core to puncture the outer membrane, resulting in membrane depolarization and eventual cell death (Fig. S1) (37,(39)(40)(41)(42)(43)(44). R-pyocins have gained interest for their potential to combat P. aeruginosa due to their powerful ability to kill target cells, their inability to replicate without a DNA-containing head, and their well-documented mechanism of action (30,31,41,(43)(44)(45).…”

Section: Introductionmentioning

confidence: 99%

High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants inPseudomonas aeruginosapopulations sourced from cystic fibrosis lung infections

Mei

Pheng

Kurzeja-Edwards

et al. 2023

Preprint

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Pseudomonas aeruginosa is a prevalent pathogen in cystic fibrosis (CF) lungs which displays strong resistance to various antibiotic classes, contributing to antimicrobial resistance (AMR). P aeruginosa populations in CF lungs exhibit considerable genetic and phenotypic diversity, raising questions about their susceptibility to non-traditional antimicrobials, such as bacteriocins. R-pyocins, bacteriocins produced by P. aeruginosa, are highly potent, non-replicating phage tail-like protein complexes with a narrow killing spectrum. The diversity of P. aeruginosa variants within CF lung infections may lead to varying susceptibility to R-pyocins due to changes in the lipopolysaccharide (LPS) structure, which acts as the R-pyocin receptor. However, the extent of susceptibility to the five known R-pyocin subtypes (R1-R5) remains unknown, especially considering the diverse P. aeruginosa populations in CF lungs. Additionally, the connection between LPS phenotype and R-pyocin susceptibility is not well understood. We tested 139 P. aeruginosa variants from 17 sputum samples of seven CF patients for R2-pyocin susceptibility and analyzed their LPS phenotypes. Our findings revealed that approximately 83% of sputum samples contained diverse P. aeruginosa populations without R2-pyocin resistant variants, while all samples had some susceptible variants. Moreover, there was no clear correlation between LPS phenotypes and R-pyocin susceptibility. The absence of a clear correlation between LPS phenotypes and R-pyocin susceptibility suggests that LPS packing density may significantly influence R-pyocin susceptibility among CF variants. Our research supports the potential use of R-pyocins as therapeutic agents, as numerous infectious CF variants appear to be susceptible to R2-pyocins, even within diverse P. aeruginosa populations.

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“…The proposed mode of action involves the R-pyocin tail fiber foot binding to a monosaccharide receptor on the lipopolysaccharide (LPS) (specific to each R-subtype), causing the sheath to contract and push the tail spike and core to puncture the outer membrane, resulting in membrane depolarization and eventual cell death (Fig. S1) ( 37 , 39 – 44 ). R-pyocins have gained interest for their potential to combat P. aeruginosa due to their powerful ability to kill target cells, their inability to replicate without a DNA-containing head, and their well-documented mechanism of action ( 30 , 31 , 41 , 43 – 45 ).…”

Section: Introductionmentioning

confidence: 99%

High prevalence of lipopolysaccharide mutants and R2-pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections

Mei,

Pheng,

Kurzeja-Edwards

et al. 2023

Microbiol Spectr

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Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality. Pseudomonas aeruginosa , a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins. R-pyocins, i.e., bacteriocins produced by P. aeruginosa , are phage-tail-like antimicrobials. R-pyocins have potential as antimicrobials, however, recent research suggests the diversity of P. aeruginosa variants within CF lung infections leads to varying susceptibility to R-pyocins. This variation may be linked to changes in lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it is unknown how frequently R-pyocin-susceptible strains are in chronic CF lung infection, particularly when considering the heterogeneity within these strains. In this study, we tested the R2-pyocin susceptibility of 139 P . aeruginosa variants from 17 sputum samples of 7 CF patients and analyzed LPS phenotypes. We found that 83% of sputum samples did not have R2-pyocin-resistant variants, while nearly all samples contained susceptible variants. There was no correlation between LPS phenotype and R2-pyocin susceptibility, though we estimate that about 76% of sputum-derived variants lack an O-specific antigen, 40% lack a common antigen, and 24% have altered LPS cores. The absence of a correlation between LPS phenotype and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Our research supports the potential of R-pyocins as therapeutic agents, as many infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations. IMPORTANCE Cystic fibrosis (CF) patients often experience chronic, debilitating lung infections caused by antibiotic-resistant Pseudomonas aeruginosa , contributing to antimicrobial resistance (AMR). The genetic and phenotypic diversity of P. aeruginosa populations in CF lungs raises questions about their susceptibility to non-traditional antimicrobials, like bacteriocins. In this study, we focused on R-pyocins, a type of bacteriocin with high potency and a narrow killing spectrum. Our findings indicate that a large number of infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations, supporting their potential use as therapeutic agents. The absence of a clear correlation between lipopolysaccharide (LPS) phenotypes and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Understanding the relationship between LPS phenotypes and R-pyocin susceptibility is crucial for developing effective treatments for these chronic infections.

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Structure of Pyocin R

Cited by 14 publications

References 0 publications

Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs

Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs

High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants inPseudomonas aeruginosapopulations sourced from cystic fibrosis lung infections

High prevalence of lipopolysaccharide mutants and R2-pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections

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