title: A Genetic Screen Reveals Novel Targets to RenderPseudomonas aeruginosaSensitive to Lysozyme and Cell Wall-Targeting Antibiotics.
abstract: Pseudomonas aeruginosais 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 prototypeP. aeruginosastrain, and identified two mutants (ΔbamBand ΔfabY) that exhibited decrease in survival after lysozyme treatment. ThebamBandfabYgenes 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 differentin vivoinfection models. The mutants also showed susceptibility to several antibiotics. Especially, ΔbamBmutant was very sensitive to vancomycin, ampicillin, and ceftazidime that target cell wall synthesis. The ΔfabYdisplayed compromised membrane integrity. In conclusion, this study uncovered a common aspect of two differentP. aeruginosamutants with pleiotropic phenotypes, and suggests that BamB and FabY could be novel potential drug targets for the treatment ofP. aeruginosainfection.
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: Kang-Mu
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of MedicineSeoul, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineSeoul, South Korea.
authors.forename: Keehoon
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of MedicineSeoul, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineSeoul, South Korea.
authors.forename: Junhyeok
authors.initials: J
authors.lastname: Go
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of MedicineSeoul, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineSeoul, South Korea; Department of Microbiology and Immunology, Severance Biomedical Science Institute, Yonsei University College of MedicineSeoul, South Korea; Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Yonsei University College of MedicineSeoul, South Korea.
authors.forename: Jeon-Soo
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineSeoul, South Korea; Department of Otorhinolaryngology, Yonsei University College of MedicineSeoul, South Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine Seoul, South Korea.
authors.forename: Hyun Jik
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of MedicineSeoul, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineSeoul, South Korea; Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Yonsei University College of MedicineSeoul, South Korea.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D002473:Cell Wall / Q000187:drug effects*; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D005820:Genetic Testing; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D009113:Muramidase / Q000494:pharmacology*; D016254:Mutagenesis, Insertional; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014640:Vancomycin / Q000494:pharmacology; D014774:Virulence; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D047090:beta-Lactams; D014640:Vancomycin; D009113:Muramidase
keywords: Pseudomonas aeruginosa; airway infection; lysozyme; multi-drug resistance; treatment regimen