The Mla system and its role in maintaining outer membrane barrier function in Stenotrophomonas maltophilia
Coves, Xavier (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Mamat, Uwe (Leibniz Lung Center)
Conchillo-Solé, Oscar (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Huedo Moreno, Pol (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Bravo, Marc (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Gómez Camacho, Andromeda Celeste (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Krohn, Ines (University Institute of Plant Science and Microbiology of Hamburg. Department of Microbiology and Biotechnology)
Streit, Wolfgang R. (University Institute of Plant Science and Microbiology of Hamburg. Department of Microbiology and Biotechnology)
Schaible, Ulrich E. (Leibniz Lung Center)
Gibert, Isidre (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Daura i Ribera, Xavier (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Yero, Daniel (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2024
Abstract:	Stenotrophomonas maltophilia are ubiquitous Gram-negative bacteria found in both natural and clinical environments. It is a remarkably adaptable species capable of thriving in various environments, thanks to the plasticity of its genome and a diverse array of genes that encode a wide range of functions. Among these functions, one notable trait is its remarkable ability to resist various antimicrobial agents, primarily through mechanisms that regulate the diffusion across cell membranes. We have investigated the Mla ABC transport system of S. maltophilia, which in other Gram-negative bacteria is known to transport phospholipids across the periplasm and is involved in maintaining outer membrane homeostasis. First, we structurally and functionally characterized the periplasmic substrate-binding protein MlaC, which determines the specificity of this system. The predicted structure of the S. maltophilia MlaC protein revealed a hydrophobic cavity of sufficient size to accommodate the phospholipids commonly found in this species. Moreover, recombinant MlaC produced heterologously demonstrated the ability to bind phospholipids. Gene knockout experiments in S. maltophilia K279a revealed that the Mla system is involved in baseline resistance to antimicrobial and antibiofilm agents, especially those with divalent-cation chelating activity. Co-culture experiments with Pseudomonas aeruginosa also showed a significant contribution of this system to the cooperation between both species in the formation of polymicrobial biofilms. As suggested for other Gram-negative pathogenic microorganisms, this system emerges as an appealing target for potential combined antimicrobial therapies.
Grants:	Agencia Estatal de Investigación PID2019-111364RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1062 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00092
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Stenotrophomonas maltophilia ; Mla system ; Biofilm ; Chelating agents ; Membrane permeability
Published in:	Frontiers in cellular and infection microbiology, Vol. 14 (February 2024) , art. 1346565, ISSN 2235-2988

DOI: 10.3389/fcimb.2024.1346565
PMID: 38469346

18 p, 5.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles