AUTHOR=Morita Yuji , Tomida Junko , Kawamura Yoshiaki 

TITLE=MexXY multidrug efflux system of Pseudomonas aeruginosa

JOURNAL=Frontiers in Microbiology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2012.00408

DOI=10.3389/fmicb.2012.00408

ISSN=1664-302X

ABSTRACT=<p>Anti-pseudomonas aminoglycosides, such as amikacin and tobramycin, are used in the treatment of <italic>Pseudomonas aeruginosa</italic> infections. However, their use is linked to the development of resistance. During the last decade, the MexXY multidrug efflux system has been comprehensively studied, and numerous reports of laboratory and clinical isolates have been published. This system has been increasingly recognized as one of the primary determinants of aminoglycoside resistance in <italic>P. aeruginosa</italic>. In <italic>P. aeruginosa</italic> cystic fibrosis isolates, upregulation of the pump is considered the most common mechanism of aminoglycoside resistance. Non-fermentative Gram-negative pathogens possessing very close MexXY orthologs such as <italic>Achromobacter xylosoxidans </italic>and various <italic>Burkholderia</italic> species (e.g., <italic>Burkholderia pseudomallei</italic> and <italic>B. cepacia</italic> complexes), but not <italic>B. gladioli</italic>, are intrinsically resistant to aminoglycosides. Here, we summarize the properties (e.g., discovery, mechanism, gene expression, clinical significance) of the <italic>P. aeruginosa</italic> MexXY pump and other aminoglycoside efflux pumps such as AcrD of <italic>Escherichia coli</italic>, AmrAB-OprA of <italic>B. pseudomallei</italic>, and AdeABC of <italic>Acinetobacter baumannii</italic>. MexXY inducibility of the PA5471 gene product, which is dependent on ribosome inhibition or oxidative stress, is noteworthy. Moreover, the discovery of the cognate outer membrane component (OprA) of MexXY in the multidrug-resistant clinical isolate PA7, serotype O12 deserves special attention.</p>