title: MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation.
abstract: OBJECTIVE
  To characterize a five gene cluster, macRS-macABCsm, in Stenotrophomonas maltophilia.
  
  
  METHODS
  The presence of macABCsm operon was verified by RT-PCR. The substrate spectrum of the MacABCsm efflux pump was investigated by mutant construction and susceptibility testing. The physiological role of MacABCsm was assessed by comparing the growth of wild-type and macABCsm mutant under different stresses. To examine the regulatory role of the two-component regulatory system (TCS) macRS in the expression of macABCsm operon, mutant construction, quantitative RT-PCR and susceptibility testing were employed.
  
  
  RESULTS
  macAsm, macBsm and macCsm genes formed a three-membered operon. The MacABCsm efflux pump extruded macrolides, aminoglycosides and polymyxins and contributed to oxidative and envelope stress tolerances and biofilm formation. Inactivation of macRS TCS hardly influenced the expression of macABCsm operon and the antimicrobial susceptibility.
  
  
  CONCLUSIONS
  The MacABCsm pump has physiological roles in protecting S. maltophilia from the attack of oxidative and envelope stresses and in biofilm formation, which may be the reason why it can be constitutively expressed in the absence of antibiotics and is highly conserved in S. maltophilia isolates isolated from different environmental niches. However, the constitutive expression of macABCsm contributes to the intrinsic resistance of S. maltophilia to macrolides, aminoglycosides and polymyxins.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yi-Tsung
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Rung-Shiuan
authors.initials: RS
authors.lastname: Liou
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 112, Taiwan tcyang@ym.edu.tw.
authors.forename: Tsuey-Ching
authors.initials: TC
authors.lastname: Yang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development*; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D009876:Operon; D011113:Polymyxins / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020615:Stenotrophomonas maltophilia / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D013312:Stress, Physiological; D013379:Substrate Specificity
chemical_list: D018528:ATP-Binding Cassette Transporters; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D018942:Macrolides; D011113:Polymyxins
keywords: antibiotics resistance; bacteria; physiological role