ClpA and HtpX Proteases Are Involved in Intrinsic Aminoglycoside Resistance of Stenotrophomonas maltophilia and Are Potential Aminoglycoside Adjuvant Targets

Hsin-Hui Huang; Yi-Tsung Lin; Peng-Ying Chen; Li-Hua Li; Hsiao-Chen Ning; Tsuey-Ching Yang

doi:10.1128/AAC.00554-18

ClpA and HtpX Proteases Are Involved in Intrinsic Aminoglycoside Resistance of Stenotrophomonas maltophilia and Are Potential Aminoglycoside Adjuvant Targets

Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00554-18. doi: 10.1128/AAC.00554-18. Print 2018 Aug.

Authors

Hsin-Hui Huang¹, Yi-Tsung Lin^{2

3}, Peng-Ying Chen¹, Li-Hua Li^{4

5}, Hsiao-Chen Ning^{6

7}, Tsuey-Ching Yang⁸

Affiliations

¹ Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
² Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
³ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁴ Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Laboratory Medicine, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan.
⁷ Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
⁸ Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan tcyang@ym.edu.tw.

Abstract

The linkage of the protease-chaperon system, SmeYZ pump, and aminoglycoside resistance was assessed in Stenotrophomonas maltophilia The clpA, clpS, clpP, and htpX genes were upregulated in response to kanamycin exposure. Of these, clpA and htpX were the primary determinants responsible for intrinsic aminoglycoside (AG) resistance. Inactivation of clpA and htpX compromised protease-mediated intrinsic aminoglycoside resistance and weakened SmeYZ pump-mediated aminoglycoside resistance, signifying HtpX and ClpA as potential AG adjuvant targets for treatment of S. maltophilia infections.

Keywords: Stenotrophomonas maltophilia; aminoglycoside resistance; chaperone; protease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoglycosides / pharmacology*
Anti-Bacterial Agents / pharmacology*
Drug Resistance, Multiple, Bacterial
Microbial Sensitivity Tests
Stenotrophomonas maltophilia / drug effects*

Substances

Aminoglycosides
Anti-Bacterial Agents