title: Geographic Differences in the Contribution of ubiA Mutations to High-Level Ethambutol Resistance in Mycobacterium tuberculosis.
abstract: Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.
authors.affiliation: Center for Emerging and Re-emerging Pathogens, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Subramanya
authors.initials: S
authors.lastname: Lingaraju
authors.affiliation: Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium Biomedical Sciences, Antwerp University, Antwerp, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Rigouts
authors.affiliation: Center for Emerging and Re-emerging Pathogens, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Section of Microbiology, International Tuberculosis Research Center, Changwon, South Korea.
authors.forename: Jongseok
authors.initials: J
authors.lastname: Lee
authors.affiliation: Management Sciences for Health, Laboratory Services, Pretoria, South Africa.
authors.forename: Alaine Nyaruhirira
authors.initials: AN
authors.lastname: Umubyeyi
authors.affiliation: Department of Biostatistics, School of Public Health, Rutgers University, Newark, New Jersey, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Davidow
authors.affiliation: Department of Biostatistics, School of Public Health, Rutgers University, Newark, New Jersey, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: German
authors.affiliation: Section of Microbiology, International Tuberculosis Research Center, Changwon, South Korea.
authors.forename: EunJin
authors.initials: E
authors.lastname: Cho
authors.affiliation: Section of Microbiology, International Tuberculosis Research Center, Changwon, South Korea.
authors.forename: Ji-Im
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Section of Microbiology, International Tuberculosis Research Center, Changwon, South Korea Department of Microbiology, Yonsei University, College of Medicine, Seoul, South Korea.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: National Masan Hospital, Changwon, South Korea.
authors.forename: Cheon Tae
authors.initials: CT
authors.lastname: Kim
authors.affiliation: Center for Emerging and Re-emerging Pathogens, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Center for Emerging and Re-emerging Pathogens, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA safiha@njms.rutgers.edu.
authors.forename: Hassan
authors.initials: H
authors.lastname: Safi
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004977:Ethambutol / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004977:Ethambutol