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Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana

Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana

来源:bioRxiv_logobioRxiv
英文摘要

Abstract BackgroundBovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen. MethodsMycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes. ResultsMycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR=2.7,p=0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients with available HIV status, the odds of isolating M. bovis from HIV patients (2/119) was 3.3 higher relative to non-HIV patients (4/774). Direct contact with livestock or their unpasteurized products was significantly associated with bTB (p<0.0001,OR=124.4,95% CI=30.1-508.3). Two (13.3%) of the M. bovis isolates were INH resistant due to the S315T mutation in katG whereas one (6.7%) was RIF resistant with Q432P and I1491S mutations in rpoB. M. bovis from Ghana resolved as mono-phyletic branch among mostly M. bovis from Africa irrespective of the host and were closest to the root of the global M. bovis phylogeny. M. bovis-specific amino acid mutations were detected among MTBC core genes such as mce1A, mmpL1, pks6, phoT, pstB, glgP and Rv2955c. Additional mutations P6T in chaA, G187E in mgtC, T35A in Rv1979c, S387A in narK1, L400F in fas and A563T in eccA1 were restricted to the 5 clinical M. bovis from Ghana. ConclusionOur data indicate potential zoonotic transmission of bTB in Ghana and hence calls for intensified public education on bTB, especially among risk groups.

Otchere Isaac Darko、S¨¢nchez-Bus¨? Leonor、Coscoll¨¢ Mireia、Osei-Wusu Stephen、Yahayah Abdallah Iddrisu、Laryea Clement、Harris Simon R、Gagneux Sebastien、Baddoo Akosua、Forson Audry、Asante-Poku Adwoa、Aboagye Samuel Yaw、Yeboah-Manu Dorothy、Parkhill Julian、Ekuban Samuel Acquah、Asare Prince、van Tonder Andries J.

Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaWellcome Sanger Institute, Wellcome Genome CampusInstitute for Integrative Systems Biology (I2SysBio), University of Valencia-CSICNoguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaChest Department, Tamale Teaching HospitalPublic Health Department, 37 Military HospitalWellcome Sanger Institute, Wellcome Genome CampusSwiss Tropical and Public Health Institute||University of BaselDepartment of Chest Diseases, Korle-Bu Teaching HospitalDepartment of Chest Diseases, Korle-Bu Teaching HospitalNoguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaNoguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaNoguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaWellcome Sanger Institute, Wellcome Genome CampusChest Department, Tamale Teaching HospitalNoguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaWellcome Sanger Institute, Wellcome Genome Campus

10.1101/489203

医学研究方法基础医学微生物学

Otchere Isaac Darko,S¨¢nchez-Bus¨? Leonor,Coscoll¨¢ Mireia,Osei-Wusu Stephen,Yahayah Abdallah Iddrisu,Laryea Clement,Harris Simon R,Gagneux Sebastien,Baddoo Akosua,Forson Audry,Asante-Poku Adwoa,Aboagye Samuel Yaw,Yeboah-Manu Dorothy,Parkhill Julian,Ekuban Samuel Acquah,Asare Prince,van Tonder Andries J..Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/489203.点此复制

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