title: Mycobacteriophage SWU1 gp39 can potentiate multiple antibiotics against Mycobacterium via altering the cell wall permeability.
abstract: M. tuberculosis is intrinsically tolerant to many antibiotics largely due to the imperviousness of its unusual mycolic acid-containing cell wall to most antimicrobials. The emergence and increasingly widespread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) revitalized keen interest in phage-inspired therapy. SWU1gp39 is a novel gene from mycobacteriophage SWU1 with unknown function. SWU1gp39 expressed in M. smegmatis conferred the host cell increased susceptibility to multiple antibiotics, including isoniazid, erythromycin, norfloxacin, ampicillin, ciprofloxacin, ofloxacin, rifampicin and vancomycin, and multiple environment stresses such as H2O2, heat shock, low pH and SDS. By using EtBr/Nile red uptake assays, WT-pAL-gp39 strain showed higher cell wall permeability than control strain WT-pAL. Moreover, the WT-pAL-gp39 strain produced more reactive oxygen species and reduced NAD(+)/NADH ratio. RNA-Seq transcriptomes of the WT-pAL-gp39 and WT-pAL revealed that the transcription of 867 genes was differentially regulated, including genes associated with lipid metabolism. Taken together, our results implicated that SWU1gp39, a novel gene from mycobacteriophage, disrupted the lipid metabolism of host and increased cell wall permeability, ultimately potentiated the efficacy of multiple antibiotics and stresses against mycobacteria.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.|School of Biological Science and Technology, University of Jinan, Shandong 250022, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Fan
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Yan
authors.affiliation: National Tuberculosis Clinical Lab of China, Beijing Key laboratory on Drug-resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism / Q000821:virology; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D010539:Permeability; D017906:Siphoviridae / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D014764:Viral Proteins