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

Authors
 Kang-Mu Lee  ;  Keehoon Lee  ;  Junhyeok Go  ;  In Ho Park  ;  Jeon-Soo Shin  ;  Jae Young Choi  ;  Hyun Jik Kim  ;  Sang Sun Yoon 
Citation
 Frontiers in Cellular and Infection Microbiology, Vol.7 : 59, 2017 
Journal Title
 Frontiers in Cellular and Infection Microbiology 
Issue Date
2017
MeSH
Animals ; Anti-Bacterial Agents/pharmacology* ; Caenorhabditis elegans ; Cell Wall/drug effects* ; DNA Transposable Elements ; Disease Models, Animal ; Gene Knockout Techniques ; Genetic Complementation Test ; Genetic Testing ; Mice, Inbred C57BL ; Microbial Viability/drug effects ; Muramidase/pharmacology* ; Mutagenesis, Insertional ; Pseudomonas Infections/microbiology ; Pseudomonas Infections/pathology ; Pseudomonas aeruginosa/drug effects* ; Pseudomonas aeruginosa/genetics* ; Pseudomonas aeruginosa/growth & development ; Pseudomonas aeruginosa/pathogenicity ; Vancomycin/pharmacology ; Virulence ; beta-Lactams/pharmacology
Keywords
Pseudomonas aeruginosa ; airway infection ; lysozyme ; multi-drug resistance ; treatment regimen
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 (ΔbamB and ΔfabY) 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, ΔbamB mutant was very sensitive to vancomycin, ampicillin, and ceftazidime that target cell wall synthesis. The ΔfabY 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.
Files in This Item:
T201700486.pdf Download
DOI
10.3389/fcimb.2017.00059
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Park, Inho(박인호) ORCID logo https://orcid.org/0000-0003-2190-5469
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Lee, Kang Mu(이강무) ORCID logo https://orcid.org/0000-0001-7414-5921
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/153958
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