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Title: Small colony variants and single nucleotide variations in Pf1 region of PB1 phage-resistant pseudomonas aeruginosa
Authors: Lim, Wee S.
Phang, Kevin K. S.
Tan, Andy Hee-Meng
Li, Sam F.-Y.
Ow, Dave S.-W.
Keywords: Phage Therapy
Pseudomonas Aeruginosa
Issue Date: 2016
Source: Lim, W. S., Phang, K. K. S., Tan, A. H.-M., Li, S. F. Y., & Ow, D. S. W. (2016). Small Colony Variants and Single Nucleotide Variations in Pf1 Region of PB1 Phage-Resistant Pseudomonas aeruginosa. Frontiers in Microbiology, 7, 282. doi: 10.3389/fmicb.2016.00282.
Series/Report no.: Frontiers in Microbiology
Abstract: Phage therapy involves the application of lytic bacteriophages for treatment of clinical infections but bacterial resistance may develop over time. Isolated from nosocomial infections, small colony variants (SCVs) are morphologically distinct, highly virulent bacterial strains that are resistant to conventional antibiotics. In this study, SCVs was derived from Pseudomonas aeruginosa exposed to the lytic bacteriophage PB1 and these cells were resistant to subsequent phage infection by PB1. To elucidate the mechanism of the SCV phage resistance, we performed phenotypic assays, DNA microarrays and whole-genome sequencing. Compared with wild-type P. aeruginosa, the SCV isolate showed impaired biofilm formation, decreased twitching motility, reduced elastase and pyocyanin production. The SCV is also more susceptible to the antibiotic ciprofloxacin and exhibited higher syrface hydrophobicity than the wild-type, indicative of changes to cell surface lipopolysaccharide (LPS) composition. Consistent with these results, transcriptomic studies of SCV revealed up-regulation of genes involved in O-specific antigen (OSA) biosynthesis, suggesting the regulation of surface moieties may account for phage resistance. Western blot analysis showed a difference in OSA distribution between the two strains. Simultaneously, genes involved in aromatic and branched chain amino acid catabolism were down-regulated. Whole genome sequencing of the SCV revealed multiple single nucleotide variations within the Pf1 prophage region, a genetic locus known to play a crucial role in biofilm formation and to provide survival advantage via gene transfer to a subpopulation of cells. Insights into phenotypic and genetic changes in SCV gained here should help direct future studies to elucidate mechanisms underpinning phage resistance, leading to novel counter resistance measures.
DOI: 10.3389/fmicb.2016.00282
Rights: © 2016 Lim, Phang, Tan, Li and Ow. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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