Role of the Cys154Arg Substitution in Ribosomal Protein L3 in Oxazolidinone Resistance in Mycobacterium tuberculosis

Gaëlle Guiewi Makafe; Yuanyuan Cao; Yaoju Tan; Mugweru Julius; Zhiyong Liu; Changwei Wang; Moses M Njire; Xingshan Cai; Tianzhou Liu; Bangxing Wang; Wei Pang; Shouyong Tan; Buchang Zhang; Wing Wai Yew; Gyanu Lamichhane; Jintao Guo; Tianyu Zhang

doi:10.1128/AAC.00152-16

Role of the Cys154Arg Substitution in Ribosomal Protein L3 in Oxazolidinone Resistance in Mycobacterium tuberculosis

Antimicrob Agents Chemother. 2016 Apr 22;60(5):3202-6. doi: 10.1128/AAC.00152-16. Print 2016 May.

Authors

Gaëlle Guiewi Makafe¹, Yuanyuan Cao², Yaoju Tan³, Mugweru Julius¹, Zhiyong Liu¹, Changwei Wang¹, Moses M Njire¹, Xingshan Cai³, Tianzhou Liu⁴, Bangxing Wang², Wei Pang⁵, Shouyong Tan³, Buchang Zhang⁶, Wing Wai Yew⁷, Gyanu Lamichhane⁸, Jintao Guo¹, Tianyu Zhang⁹

Affiliations

¹ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
² State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China School of Life Sciences, Anhui University, Hefei, China.
³ State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, The Guangzhou Chest Hospital, Guangzhou, China.
⁴ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China School of Life Sciences, University of Science and Technology of China, Hefei, China.
⁵ Langfang Yanjing Vocational and Technical College, Langfang, China Forensic Medical Center, University of Maryland, Baltimore, Maryland, USA.
⁶ School of Life Sciences, Anhui University, Hefei, China.
⁷ Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
⁸ School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
⁹ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China zhang_tianyu@gibh.ac.cn.

Abstract

We expressed the wild-type rplC and mutated rplC (Cys154Arg) genes, respectively, in Mycobacterium tuberculosis H37Ra and H37Rv in an attempt to delineate the role of rplC (Cys154Arg) regarding oxazolidinone resistance. An increase of the MICs of linezolid (LZD) and sutezolid (PNU-100480, PNU) against the recombinant mycobacteria with overexpressed rplC mutation (Cys154Arg) was found, suggesting the rplC gene is a determinant of bacillary susceptibilities to LZD and PNU.

MeSH terms

Antitubercular Agents / pharmacology*
Linezolid / pharmacology
Microbial Sensitivity Tests
Mutation
Mycobacterium tuberculosis / drug effects
Mycobacterium tuberculosis / genetics
Mycobacterium tuberculosis / metabolism*
Oxazolidinones / pharmacology*
Ribosomal Protein L3
Ribosomal Proteins / genetics
Ribosomal Proteins / metabolism*

Substances

Antitubercular Agents
Oxazolidinones
PNU-100480
Ribosomal Protein L3
Ribosomal Proteins
Linezolid

Grants and funding

DP2 OD008459/OD/NIH HHS/United States