PDF(Pubmed)
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.
摘要：
嗜麦芽窄食单胞菌是在自然和临床环境中发现的普遍存在的革兰氏阴性细菌。它是一个非常适应的物种，能够在各种环境中茁壮成长，由于其基因组的可塑性和编码多种功能的多种基因。在这些功能中，一个值得注意的特点是其显著的抵抗各种抗菌剂的能力，主要通过调节跨细胞膜扩散的机制。我们已经调查了嗜麦芽窄食链球菌的MlaABC转运系统，在其他革兰氏阴性菌中，已知磷脂穿过周质运输，并参与维持外膜稳态。首先,我们在结构和功能上表征了周质底物结合蛋白MlaC，这决定了这个系统的特殊性。嗜麦芽窄食链球菌MlaC蛋白的预测结构揭示了一个疏水腔，其大小足以容纳该物种中常见的磷脂。此外，异源产生的重组MlaC证明了结合磷脂的能力。嗜麦芽窄食链球菌K279a的基因敲除实验表明，Mla系统参与了对抗菌药物和抗生物膜药物的基线抗性，特别是那些具有二价阳离子螯合活性的。与铜绿假单胞菌的共培养实验也表明，该系统对两种物种之间在形成微生物生物膜方面的合作做出了重大贡献。正如其他革兰氏阴性病原微生物所建议的那样，该系统成为潜在的联合抗菌治疗的一个有吸引力的目标.
