Efflux pump systems as key contributors to multidrug resistance in Stenotrophomonas maltophilia: Physiological roles and gene regulation.

Abstract

Stenotrophomonas maltophilia has emerged as an opportunistic pathogen originating from the environments, causing nosocomial infections, particularly in immunocompromised individuals and patients with cystic fibrosis. Although this microorganism exhibits low virulence, its infections are associated with high morbidity and mortality rates. S. maltophilia is intrinsically resistant to many antimicrobial agents used in clinical practices, therefore, posing significant treatment challenges. The multidrug resistance in S. maltophilia results from a combination of intrinsic, adaptive, and acquired mechanisms. S. maltophilia genome carries an array of genes encoding multidrug efflux pumps, which are key contributors to its broad-spectrum antibiotic resistance by expelling a wide range of drugs and reducing their intracellular concentrations to nontoxic levels. The majority of these efflux pumps belong to the resistance-nodulation-cell division (RND) family, while a lesser fraction is classified under the major facilitator superfamily (MFS) and the adenosine triphosphate binding cassette (ABC) family. In terms of function, substrate specificity, and complex gene regulation, these multidrug efflux pumps contribute not only to the survival of S. maltophilia under antibiotic stress but also to its resilience against other chemical challenges, including oxidative stress-generating substances and biocides. The roles of certain efflux pump systems in acquired and adaptive antibiotic resistance, as well as their potential applications as drug targets to enhance the efficacy of routinely used antibiotics through the use of small molecules capable of functioning as efflux pump inhibitors, are also discussed. A deeper understanding of these mechanisms can contribute to the more effective management against antibiotic-resistant S. maltophilia.