國家衛生研究院 NHRI:Item 3990099045/6114

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Title:	Interplay between mutational and horizontally acquired resistance mechanisms and its association with carbapenem resistance amongst extensively drug-resistant Pseudomonas aeruginosa (XDR-PA)
Authors:	Shu, JC;Chia, JH;Siu, LK;Kuo, AJ;Huang, SH;Su, LH;Wu, TL
Contributors:	Division of Infectious Diseases
Abstract:	Between 2003 and 2009, the prevalence of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) increased significantly in northern Taiwan from 1.0% to 2.1%. Molecular methods were used to investigate the genetic relatedness and carbapenem resistance mechanisms of a collection of 203 non-repetitive XDR-PA isolates available for study. Using pulsed-field gel electrophoresis (PFGE), 52 genotypes were observed; one predominant genotype (pulsotype 1) was found in 57.6% of the isolates. Polymerase chain reaction (PCR), sequencing and quantitative reverse-transcriptase PCR analyses demonstrated that one horizontally acquired mechanism [metallo-β-lactamase (MBL) genes] and two mutational mechanisms (efflux and porins) accounted for the carbapenem resistance. The most predominant horizontally acquired mechanism was carriage of blaVIM-3, which was found in 61.1% of isolates. Decreased expression of oprD was the most prevalent mutational mechanism and was found in 70.0% of the XDR-PA isolates, whereas overexpression of mexA was found in 27.6% of the isolates. The highlight of this study was the discovery of statistically significant relationships between certain horizontally acquired and mutational resistance mechanisms and their contribution to carbapenem susceptibility. MBL-producers expressed significantly lower MexAB and higher OprD than non-MBL-producers. Amongst isolates without an acquired β-lactamase gene, oprD expression was significantly reduced, whilst expression of efflux pumps was increased. Reduced OprD expression alone or the production of VIM-type MBLs showed similar contributions to a low to intermediate MIC50 (minimum inhibitory concentration for 50% of the organisms) for carbapenems. Isolates with reduced OprD expression that simultaneously harboured blaVIM exhibited high levels of resistance to carbapenems, which implied that these two mechanisms had a synergistic effect on the MICs.
Date:	2012-03
Relation:	International Journal of Antimicrobial Agents. 2012 Mar;39(3):217-222.
Link to:	http://dx.doi.org/10.1016/j.ijantimicag.2011.09.023
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0924-8579&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000300587100006
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84857058336
Appears in Collections:	[Leung-Kei Siu] Periodical Articles

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