title: Pleiotropic effects of temperature-regulated 2-OH-lauroytransferase (PA0011) on Pseudomonas aeruginosa antibiotic resistance, virulence and type III secretion system.
abstract: Pseudomonas aeruginosa is an important human pathogen which adapts to changing environment, such as temperature variations and entering host by regulating their gene expression. Here, we report that gene PA0011 in P. aeruginosa PAO1, which encodes a 2-OH-lauroytransferase participating in lipid A biosynthesis, is involved in carbapenem resistance and virulence in a temperature-regulated manner in PAO1. The expression of PA0011 was higher at an environment temperature (21 °C) than that at a body temperature (37 °C). The inactivation of PA0011 rendered increased antibiotic susceptibility and decreased virulence both in vivo and in vitro. The impaired integrity and the decreased stability of the outer membrane were the cause of the increased susceptibility of PAO1(Δ0011) to carbapenem and many other common antibiotics. The reduced endotoxic activity of lipopolysaccharide (LPS) contributed to the decreased virulence both at 21 °C and 37 °C in PAO1 (Δ0011). In addition, we have found that PA0011 repressed the expression of TTSS virulence factors both at transcriptional and translational levels, similar to the effect of O antigen of LPS but unlike any effect of its homologue reported in other bacteria. The effect of PA0011 on resistance to many antibiotics including carbapenem and virulence in P. aeruginosa makes it a target for novel antimicrobial therapies.
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Bobo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Gao
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China; Department of Oral Biology; Department of Medical Microbiology, University of Manitoba, 780 Bannatyne Ave., Winnipeg, MB, R3E 0W2, Canada. Electronic address: kduan@nwu.edu.cn.
authors.forename: Kangmin
authors.initials: K
authors.lastname: Duan
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, 710069, China. Electronic address: shenlx@nwu.edu.cn.
authors.forename: Lixin
authors.initials: L
authors.lastname: Shen
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D024881:Drug Resistance, Bacterial; D004795:Enzyme Stability; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D013696:Temperature; D000069296:Type III Secretion Systems / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000069296:Type III Secretion Systems; D000217:Acyltransferases
keywords: Antibiotic resistance; Pseudomonas aeruginosa; Temperature; Virulence