Open AccessA mutation in anti-sigma factor MAB_3542c may be responsible for tigecycline resistance in Mycobacterium abscessus
Author(s) -
Hien Fuh Ng,
Joon Liang Tan,
Thaw Zin,
Sook Fan Yap,
Yun Fong Ngeow
Publication year - 2018
Publication title -
journal of medical microbiology/journal of medical microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.91
H-Index - 117
eISSN - 1473-5644
pISSN - 0022-2615
DOI - 10.1099/jmm.0.000857
Subject(s) - tigecycline , mutant , mycobacterium tuberculosis , microbiology and biotechnology , biology , mutation , mycobacterium abscessus , point mutation , sigma factor , wild type , genetics , gene , mycobacterium , antibiotics , promoter , tuberculosis , bacteria , medicine , gene expression , pathology
In this study, we characterized 7C, a spontaneous mutant selected from tigecycline-susceptible Mycobacterium abscessus ATCC 19977. Whole-genome sequencing (WGS) was used to identify possible resistance determinants in this mutant. Compared to the wild-type, 7C demonstrated resistance to tigecycline as well as cross-resistance to imipenem, and had a slightly retarded growth rate. WGS and subsequent biological verifications showed that these phenotypes were caused by a point mutation in MAB_3542c, which encodes an RshA-like protein. In Mycobacterium tuberculosis, RshA is an anti-sigma factor that negatively regulates the heat/oxidative stress response mechanisms. The MAB_3542c mutation may represent a novel determinant of tigecycline resistance. We hypothesize that this mutation may dysregulate the stress-response pathways which have been shown to be linked to antibiotic resistance in previous studies.