AmgRS‐mediated envelope stress‐inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa. Issue 1 (1st December 2014)

• Record Type: Journal Article
• Authors: Lau, Calvin Ho‐Fung; Krahn, Thomas; Gilmour, Christie; Mullen, Erin; Poole, Keith
• Is Part Of: MicrobiologyOpen. Volume 4:Issue 1(2015:Feb.)
• Page Start: 121
• Page End: 135
• Publication Date: 2014-12-01
• Subjects: Microbiology -- Periodicals; 579
• DOI: 10.1002/mbo3.226
• Languages: English
• ISSNs: 2045-8827

Abstract

<abstract abstract-type="main" id="mbo3226-abs-0001"> <title>Abstract</title> <p>AmgRS is an envelope stress‐responsive two‐component system and aminoglycoside resistance determinant in <italic>Pseudomonas aeruginosa</italic> that is proposed to protect cells from membrane damage caused by aminoglycoside‐generated mistranslated polypeptides. Consistent with this, a Δ<italic>amgR</italic> strain showed increased aminoglycoside‐promoted membrane damage, damage that was largely absent in AmgRS‐activated <italic>amgS‐</italic>mutant strains. Intriguingly, one such mutation, V121G, while providing for enhanced resistance to aminoglycosides, rendered <italic>P. aeruginosa</italic> susceptible to several ribosome‐targeting nonaminoglycoside antimicrobials that are inducers and presumed substrates of the MexXY‐OprM multidrug efflux system. Surprisingly, the <italic>amg</italic><italic>S</italic><sub>V</sub><sub>121G</sub> mutation increased <italic>mexXY</italic> expression threefold, suggesting that export of these nonaminoglycosides was compromised in the <italic>amg</italic><italic>S</italic><sub>V</sub><sub>121G</sub> mutant. Nonetheless, a link was established between AmgRS activation and <italic>mexXY</italic> expression and this was confirmed in studies showing that aminoglycoside‐promoted <italic>mexXY</italic> expression is dependent on AmgRS. While nonaminoglycosides also induced <italic>mexXY</italic> expression, this was not AmgRS‐dependent, consistent with these agents not generating mistranslated polypeptides and not activating AmgRS. The aminoglycoside inducibility of <italic>mexXY</italic> was abrogated in a mutant lacking the AmgRS target genes <italic>htpX</italic> and PA5528, encoding a presumed cytoplasmic membrane‐associated protease and a membrane protein of unknown function, respectively. Thus, aminoglycoside induction of <italic>mexXY</italic> is a response to membrane damage and activation of the AmgRS two‐component system.</p> </abstract>