title: Transcription-associated mutation of lasR in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen which infects cystic fibrosis and cancer patients with compromised immune systems. LasR is a master regulator which controls the virulence of P. aeruginosa in response to bacterial cell-density and host signals. During infection, lasR is frequently mutated, conferring P. aeruginosa a growth advantage in hosts and enhances resistance to widely used antibiotics. However, the mechanistic basis of lasR mutation is not well understood. We have tested here the hypothesis that transcription strength is a contributory determinant of lasR mutagenesis. P. aeruginosa strains with different lasR transcription strengths were therefore engineered and the lasR mutations were monitored unbiasedly using next-generation sequencing technology. Our results suggest that the strength of transcription could be one of the deterministic factors that drive the mutagenesis of lasR in P. aeruginosa, shedding new insights into bacterial infection and antibiotic resistance.
authors.affiliation: Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 169610, Singapore.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 169857, Singapore.
authors.forename: John R
authors.initials: JR
authors.lastname: McPherson
authors.affiliation: Institute of Molecular and Cell Biology, Biopolis, 138673, Singapore; Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, 510642, China.
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 169857, Singapore.
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.affiliation: Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 169610, Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 169857, Singapore; Institute of Molecular and Cell Biology, Biopolis, 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore. Electronic address: cmrksb@nccs.com.sg.
authors.forename: Kanaga
authors.initials: K
authors.lastname: Sabapathy
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness; D059014:High-Throughput Nucleotide Sequencing; D009154:Mutation; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; C081237:LasI protein, Pseudomonas aeruginosa; C080365:LasR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D015534:Trans-Activators; C118377:rsaL protein, Pseudomonas aeruginosa
keywords: Miseq; Next generation sequencing; Pseudomonas aeruginosa; Quorum sensing; Transcription-associated mutation