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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473628.do
DOI
10.3389/fcimb.2017.00059
Title
A Genetic Screen Reveals Novel Targets to Render Pseudomonas aeruginosaSensitive to Lysozyme and Cell Wall-Targeting Antibiotics
Description
This work was supported by grants from the National Research Foundation(NRF) of Korea, funded by the Korean government (2014R1A2A2A01002861,2014R1A4A1008625, and 2014R1A1A2059520). This work was also madepossible by a grant from the Korea Healthcare Technology R&D Project ofthe Ministry for Health, Welfare, and Family Affairs (HI15C0694).
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 (Delta bamB and Delta 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, Delta bamB mutant was very sensitive to vancomycin, ampicillin, and ceftazidime that target cell wall synthesis. The 1 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.
provenance
Made available in Cube on 2018-09-28T10:24:41Z (GMT). No. of bitstreams: 0
language
English
author
Lee, Kang-Mu
Lee, Keehoon
Go, Junhyeok
Park, In Ho
Shin, Jeon-Soo
Choi, Jae Young
Kim, Hyun Jik
Yoon, Sang Sun
accessioned
2018-09-28T10:24:41Z
available
2018-09-28T10:24:41Z
issued
2017
citation
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY(7)
issn
2235-2988
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473628.do
Funder
보건복지부
Funding Program
질환극복기술개발
Project ID
1465024091
Jurisdiction
Rep.of Korea
Project Name
Chemical optiimization of a Pseudomonas aeruginosa elastase inhibitor and development of iron acquisition inhibitors
rights
openAccess
subject
Pseudomonas aeruginosa
lysozyme
treatment regimen
airway infection
multi-drug resistance
type
article


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