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A Genetic Screen Reveals Novel Targets to Render Pseudomonas aeruginosa Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics.

ABSTRACT: Pseudomonas aeruginosa is capable of establishing airway infections. Human airway mucus contains a large amount of lysozyme, which hydrolyzes bacterial cell walls. P. aeruginosa, however, is known to be resistant to lysozyme. Here, we performed a genetic screen using a mutant library of PAO1, a prototype P. aeruginosa strain, and identified two mutants (?bamB and ?fabY) that exhibited decrease in survival after lysozyme treatment. The bamB and fabY genes encode an outer membrane assembly protein and a fatty acid synthesis enzyme, respectively. These two mutants displayed retarded growth in the airway mucus secretion (AMS). In addition, these mutants exhibited reduced virulence and compromised survival fitness in two different in vivo infection models. The mutants also showed susceptibility to several antibiotics. Especially, ?bamB mutant was very sensitive to vancomycin, ampicillin, and ceftazidime that target cell wall synthesis. The ?fabY displayed compromised membrane integrity. In conclusion, this study uncovered a common aspect of two different P. aeruginosa mutants with pleiotropic phenotypes, and suggests that BamB and FabY could be novel potential drug targets for the treatment of P. aeruginosa infection.

SUBMITTER: Lee KM

PROVIDER: S-EPMC5331053 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Genetic Screen Reveals Novel Targets to Render Pseudomonas aeruginosa Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics.

Lee Kang-Mu KM Lee Keehoon K Go Junhyeok J Park In Ho IH Shin Jeon-Soo JS Choi Jae Young JY Kim Hyun Jik HJ Yoon Sang Sun SS

Frontiers in cellular and infection microbiology 20170301

Pseudomonas aeruginosa is capable of establishing airway infections. Human airway mucus contains a large amount of lysozyme, which hydrolyzes bacterial cell walls. P. aeruginosa, however, is known to be resistant to lysozyme. Here, we performed a genetic screen using a mutant library of PAO1, a prototype P. aeruginosa strain, and identified two mutants (ΔbamB and ΔfabY) that exhibited decrease in survival after lysozyme treatment. The bamB and fabY</i ...[more]

PMID: 28299285

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A Genetic Screen Reveals Novel Targets to Render Pseudomonas aeruginosa Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics.

Publications

A Genetic Screen Reveals Novel Targets to Render <i>Pseudomonas aeruginosa</i> Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics.

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