Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials.
Multidrug efflux pumps constitute a group of transporters that are ubiquitously found in any organism. In addition to other functions with relevance for the cell physiology, efflux pumps contribute to the resistance to compounds used for treating different diseases, including resistance to anticancer drugs, antibiotics or antifungal compounds. In the case of antimicrobials, efflux pumps are major players in both intrinsic and acquired resistance to drugs currently in use for the treatment of infectious diseases. One important aspect not fully explored of efflux pumps consists on the identification of effectors able to induce their expression. Indeed, whereas the analysis of clinical isolates have shown that mutants overexpressing these resistance elements are frequently found, less is known on the conditions that may trigger expression of efflux pumps, hence leading to transient induction of resistance in vivo, a situation that is barely detectable using classical susceptibility tests. In the current article we review the structure and mechanisms of regulation of the expression of bacterial and fungal efflux pumps, with a particular focus in those for which a role in clinically relevant resistance has been reported.
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Sara
S
Hernando-Amado
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Paula
P
Blanco
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Manuel
M
Alcalde-Rico
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Fernando
F
Corona
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Jose A
JA
Reales-Calderón
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
María B
MB
Sánchez
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain. Electronic address: jlmtnez@cnb.csic.es.
José L
JL
Martínez
D000890:Anti-Infective Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D026141:Drug Resistance, Multiple, Fungal / Q000187:drug effects / Q000235:genetics*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005658:Fungi / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D015964:Gene Expression Regulation, Bacterial; D015966:Gene Expression Regulation, Fungal; D019450:Genes, MDR; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D006801:Humans; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D005656:Fungal Proteins
Antibiotic resistance; Bacterial virulence; Multidrug efflux pumps; Resistance to antifungals