AUTHOR=Lee Kang-Mu , Lee Keehoon , Go Junhyeok , Park In Ho , Shin Jeon-Soo , Choi Jae Young , Kim Hyun Jik , Yoon Sang Sun 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00059

DOI=10.3389/fcimb.2017.00059

ISSN=2235-2988

ABSTRACT=<p><italic>Pseudomonas aeruginosa</italic> is capable of establishing airway infections. Human airway mucus contains a large amount of lysozyme, which hydrolyzes bacterial cell walls. <italic>P. aeruginosa</italic>, however, is known to be resistant to lysozyme. Here, we performed a genetic screen using a mutant library of PAO1, a prototype <italic>P. aeruginosa</italic> strain, and identified two mutants (Δ<italic>bamB</italic> and Δ<italic>fabY</italic>) that exhibited decrease in survival after lysozyme treatment. The <italic>bamB</italic> and <italic>fabY</italic> 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 <italic>in vivo</italic> infection models. The mutants also showed susceptibility to several antibiotics. Especially, Δ<italic>bamB</italic> mutant was very sensitive to vancomycin, ampicillin, and ceftazidime that target cell wall synthesis. The Δ<italic>fabY</italic> displayed compromised membrane integrity. In conclusion, this study uncovered a common aspect of two different <italic>P. aeruginosa</italic> mutants with pleiotropic phenotypes, and suggests that BamB and FabY could be novel potential drug targets for the treatment of <italic>P. aeruginosa</italic> infection.</p>