Abstract
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.
Highlights
Efflux pump systems are present in all organisms and recognized to transport a range of structurally unrelated compounds and confer clinically relevant resistances to antimicrobial agents
The resistance nodulation division (RND) efflux pumps consist of a RND-type transporter protein, which is located in the inner membrane; a membrane-fusion protein (MFP), which is located in the periplasmic space; and an outer membrane protein, which is located in the outer membrane of the bacterium
For the MuxABC pump of P. aeruginosa, both the two RND components are essential for its function [23]
Summary
Efflux pump systems are present in all organisms and recognized to transport a range of structurally unrelated compounds and confer clinically relevant resistances to antimicrobial agents. There are five families of efflux pumps associated with multidrug resistance (MDR): the ATP binding cassette (ABC) family, the multidrug and toxic-compound extrusion (MATE) family, the major facilitator (MFS) family, the resistance nodulation division (RND) family, and the small multidrug resistance (SMR) family [1]. The RND efflux pumps consist of a RND-type transporter protein, which is located in the inner membrane; a membrane-fusion protein (MFP), which is located in the periplasmic space; and an outer membrane protein, which is located in the outer membrane of the bacterium. Many studies have evidenced that the RND-type efflux pumps confer resistance to drugs and have a physiological role in stress adaption [2].
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