TY - JOUR
T1 - Role of smeU1VWU2X operon in alleviation of oxidative stresses and occurrence of sulfamethoxazole-trimethoprim-resistant mutants in stenotrophomonas maltophilia
AU - Wu, Chao Jung
AU - Chiu, Tsu Ting
AU - Lin, Yi Tsung
AU - Huang, Yi Wei
AU - Li, Li Hua
AU - Yang, Tsuey Ching
N1 - Funding Information:
This study was funded by grant MOST 104-2320-B-010-023-MY3 from the Ministry of Science and Technology of Taiwan and grant 30219003 from the Tsuei-Chu Mong Merit Scholarship.
Publisher Copyright:
Copyright © 2018 American Society for Microbiology. All Rights Reserved.
PY - 2018/2
Y1 - 2018/2
N2 - Overexpression of resistance-nodulation-division (RND)-type efflux pumps is an important mechanism for bacteria to combat antimicrobials. RND efflux pumps are also critical for bacterial physiology, such as oxidative stress tolerance. Stenotrophomonas maltophilia, a multidrug-resistant opportunistic pathogen, harbors eight RND-type efflux pump operons. Of these, the smeU1VWU2X operon is unique for its possession of two additional genes, smeU1 and smeU2, which encode proteins of the short-chain dehydrogenase/reductase (SDR) family. Overexpression of the SmeVWX pump is known to contribute to the acquired resistance to chloramphenicol, quinolone, and tetracycline; however, SmeU1 and SmeU2 are little involved in this phenotype. In the study described in this article, we further linked the smeU1VWU2X operon to oxidative stress alleviation and sulfamethoxazole-trimethoprim (SXT)resistant mutant occurrence. The smeU1VWU2X operon was inducibly expressed upon challenge with menadione (MD), plumbagin (PL), and hydrogen peroxide (H 2 O 2 ), as verified by the use of the chromosomal smeU1VWU2X-xylE transcriptional fusion construct and quantitative real-time PCR (qRT-PCR). The MD-mediated smeU1VWU2X upexpression was totally dependent on SoxR and partially relied on SmeRv but was less relevant to OxyR. SmeRv, but not SoxR and OxyR, played a regulatory role in the H 2 O 2 -mediated smeU1VWU2X upexpression. The significance of smeU1VWU2X upexpression was investigated with respect to oxidative stress alleviation and SXT-resistant mutant occurrence. Overexpression of the smeU1VWU2X operon contributed to the alleviation of MD-mediated oxidative stress. Of the encoded proteins, the SmeVWX pump and SmeU2, rather than SmeU1, participated in MD tolerance. Furthermore, we also demonstrated that the MD-mediated expression of the smeU1VWU2X operon decreased the SXT resistance frequency when S. maltophilia was grown in a reactive oxygen species (ROS)-rich environment.
AB - Overexpression of resistance-nodulation-division (RND)-type efflux pumps is an important mechanism for bacteria to combat antimicrobials. RND efflux pumps are also critical for bacterial physiology, such as oxidative stress tolerance. Stenotrophomonas maltophilia, a multidrug-resistant opportunistic pathogen, harbors eight RND-type efflux pump operons. Of these, the smeU1VWU2X operon is unique for its possession of two additional genes, smeU1 and smeU2, which encode proteins of the short-chain dehydrogenase/reductase (SDR) family. Overexpression of the SmeVWX pump is known to contribute to the acquired resistance to chloramphenicol, quinolone, and tetracycline; however, SmeU1 and SmeU2 are little involved in this phenotype. In the study described in this article, we further linked the smeU1VWU2X operon to oxidative stress alleviation and sulfamethoxazole-trimethoprim (SXT)resistant mutant occurrence. The smeU1VWU2X operon was inducibly expressed upon challenge with menadione (MD), plumbagin (PL), and hydrogen peroxide (H 2 O 2 ), as verified by the use of the chromosomal smeU1VWU2X-xylE transcriptional fusion construct and quantitative real-time PCR (qRT-PCR). The MD-mediated smeU1VWU2X upexpression was totally dependent on SoxR and partially relied on SmeRv but was less relevant to OxyR. SmeRv, but not SoxR and OxyR, played a regulatory role in the H 2 O 2 -mediated smeU1VWU2X upexpression. The significance of smeU1VWU2X upexpression was investigated with respect to oxidative stress alleviation and SXT-resistant mutant occurrence. Overexpression of the smeU1VWU2X operon contributed to the alleviation of MD-mediated oxidative stress. Of the encoded proteins, the SmeVWX pump and SmeU2, rather than SmeU1, participated in MD tolerance. Furthermore, we also demonstrated that the MD-mediated expression of the smeU1VWU2X operon decreased the SXT resistance frequency when S. maltophilia was grown in a reactive oxygen species (ROS)-rich environment.
KW - Efflux pumps
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85041005497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041005497&partnerID=8YFLogxK
U2 - 10.1128/AAC.02114-17
DO - 10.1128/AAC.02114-17
M3 - Article
C2 - 29203487
AN - SCOPUS:85041005497
SN - 0066-4804
VL - 62
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 2
M1 - e02114-17
ER -
