A linkage between SmeIJK efflux pump, cell envelope integrity, and σE-mediated envelope stress response in Stenotrophomonas maltophilia.
Resistance nodulation division (RND) efflux pumps, such as the SmeIJK pump of Stenotrophomonas maltophilia, are known to contribute to the multidrug resistance in Gram-negative bacteria. However, some RND pumps are constitutively expressed even though no antimicrobial stresses occur, implying that there should be some physical implications for these RND pumps. In this study, the role of SmeIJK in antimicrobials resistance, envelope integrity, and σE-mediated envelope stress response (ESR) of S. maltophilia was assessed. SmeIJK was involved in the intrinsic resistance of S. maltophilia KJ to aminoglycosides and leucomycin. Compared with the wild-type KJ, the smeIJK deletion mutant exhibited growth retardation in the MH medium, an increased sensitivity to membrane-damaging agents (MDAs), as well as activation of an σE-mediated ESR. Moreover, the expression of smeIJK was further induced by sub-lethal concentrations of MDAs or surfactants in an σE-dependent manner. These data collectively suggested an alternative physiological role of smeIJK in cell envelope integrity maintenance and σE-mediated ESR beyond the efflux of antibiotics. Because of the necessity of the physiological role of SmeIJK in protecting S. maltophilia from the envelope stress, smeIJK is constitutively expressed, which, in turn, contributes the intrinsic resistance to aminoglycoside and leucomycin. This is the first demonstration of the linkage among RND-type efflux pump, cell envelope integrity, and σE-mediated ESR in S. maltophilia.
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Yi-Wei
YW
Huang
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Rung-Shiuan
RS
Liou
Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Yi-Tsung
YT
Lin
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsin-Hui
HH
Huang
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Tsuey-Ching
TC
Yang
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D050557:Catechol 2,3-Dioxygenase / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003091:Colistin / Q000737:chemistry; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009876:Operon; D009995:Osmosis; D012808:Sigma Factor / Q000378:metabolism*; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D012808:Sigma Factor; C063202:sporulation-specific sigma factors; D050557:Catechol 2,3-Dioxygenase; D003091:Colistin