加纳临床分离牛分枝杆菌的分子流行病学和全基因组测序分析。
Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana.
机构信息
Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
出版信息
PLoS One. 2019 Mar 4;14(3):e0209395. doi: 10.1371/journal.pone.0209395. eCollection 2019.
BACKGROUND
Bovine 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.
METHODS
Mycobacterium 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 isolates were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes.
RESULTS
Mycobacterium 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.
CONCLUSION
Our data indicate potential zoonotic transmission of bTB in Ghana and hence calls for intensified public education on bTB, especially among risk groups.
背景
由牛分枝杆菌引起的牛结核病（bTB）在牲畜和人类中再次出现。一些牛分枝杆菌菌株与高致病性、耐多药结核病和播散性疾病有关，这使得了解病原体的生物学特性变得至关重要。
方法
对 2012 年至 2014 年间分离的 1755 株结核分枝杆菌复合体（MTBC）中的 15 株牛分枝杆菌进行了特征分析，并对相关患者的人口统计学和其他危险因素进行了分析。对 5 株牛分枝杆菌进行了全基因组测序，并与全球已发表的牛分枝杆菌基因组进行了比较分析。
结果
牛分枝杆菌从 3/560（0.5%）名女性和 12/1195（1.0%）名男性肺结核患者中分离出来。牛分枝杆菌感染病例的平均年龄为 46.8 岁（7-72 岁）。加纳北部地区（2.7%；4/212）的结核病患者比阿克拉地区（0.7%；11/1543）的结核病患者更有可能感染牛分枝杆菌（OR=2.7，p=0.0968）。在有 HIV 检测结果的结核病患者中，与非 HIV 患者（4/774）相比，从 HIV 患者中分离出牛分枝杆菌（2/119）的几率高 3.3 倍。与牲畜直接接触或其未经巴氏消毒的产品与 bTB 显著相关（p<0.0001，OR=124.4，95%CI=30.1-508.3）。两株（13.3%）牛分枝杆菌因 katG 中的 S315T 突变而对 INH 耐药，一株（6.7%）因 rpoB 中的 Q432P 和 I1491S 突变而对 RIF 耐药。来自加纳的牛分枝杆菌在非洲的大多数牛分枝杆菌中形成单系分支，而与宿主无关，并且与全球牛分枝杆菌系统发育树的根部最为接近。在 MTBC 核心基因（如 mce1A、mmpL1、pks6、phoT、pstB、glgP 和 Rv2955c）中检测到牛分枝杆菌特有的氨基酸突变。此外，在 chaA 中的 P6T、mgtC 中的 G187E、Rv1979c 中的 T35A、narK1 中的 S387A、fas 中的 L400F 和 eccA1 中的 A563T 突变仅局限于来自加纳的 5 株临床牛分枝杆菌。
结论
我们的数据表明，加纳存在牛结核病的潜在人畜共患病传播，因此需要加强公众对牛结核病的教育，特别是针对高危人群。
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