Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.238956v1?rss=1 Authors: Mei, M., Thomas, J., Diggle, S. P. Abstract: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen and a major determinant of declining lung function in individuals with cystic fibrosis (CF). P. aeruginosa possesses many intrinsic antibiotic resistance mechanisms, and isolates from chronic CF lung infections develop increasing resistance to multiple antibiotics over time, making new treatment approaches necessary. R-type pyocins are narrow spectrum, phage tail-like bacteriocins, specifically produced by P. aeruginosa to kill other strains of P. aeruginosa. Due to their specific anti-pseudomonal activity and similarity to bacteriophage, R-pyocins have potential as additional therapeutics against P. aeruginosa, either in isolation, in combination with antibiotics, or as an alternative to phage therapy. While it is increasingly acknowledged that colonizing P. aeruginosa populations become both phenotypically and genetically diverse during chronic infection of the CF lung, little is known about the efficacy of R-pyocins against heterogenous populations of P. aeruginosa. To investigate this, we first evaluated the distribution of R-pyocin subtypes in different environments, by bioinformatically R-pyocin typing single strains from the International Pseudomonas Consortium Database (IPCD). We found that R1-type pyocins are the most prevalent across strains from all environments, including those sourced from CF. We corroborated these findings by R-pyocin typing whole populations of CF strains from our own biobank of isolates sourced from expectorated CF sputum and found that (i) R1-pyocins were the most prevalent R-type among our CF strains and (ii) isolates of P. aeruginosa from whole populations collected from the same patient have the same R-pyocin type. Moreover, we found heterogeneity in susceptibility to R-pyocins within populations of P. aeruginosa, which is likely due to differences in the lipopolysaccharide (LPS), supporting the idea that the core of the LPS is the receptor for R-pyocins. Our findings suggest there is likely heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, and increases our understanding of the potential of bacteriophage and other phage-like, LPS-binding antimicrobial particles as novel alternative therapies in CF. Copy rights belong to original authors. Visit the link for more info