Institute of Tropical Medicine, Antwerp, Belgium ; Medical Research Council Unit, Fajara, The Gambia.
PLoS Negl Trop Dis. 2013 May 16;7(5):e2220. doi: 10.1371/journal.pntd.0002220. Print 2013.
Human tuberculosis (TB) in West Africa is not only caused by M. tuberculosis but also by bacteria of the two lineages of M. africanum. For instance, in The Gambia, 40% of TB is due to infections with M. africanum West African 2. This bacterial lineage is associated with HIV infection, reduced ESAT-6 immunogenicity and slower progression to active disease. Although these characteristics suggest an attenuated phenotype of M. africanum, no underlying mechanism has been described. From the first descriptions of M. africanum in the literature in 1969, the time to a positive culture of M. africanum on solid medium was known to be longer than the time to a positive culture of M. tuberculosis. However, the delayed growth of M. africanum, which may correlate with the less virulent phenotype in the human host, has not previously been studied in detail.
METHODOLOGY/PRINCIPAL FINDINGS: We compared the growth rates of M. tuberculosis and M. africanum isolates from The Gambia in two liquid culture systems. M. africanum grows significantly slower than M. tuberculosis, not only when grown directly from sputa, but also in growth experiments under defined laboratory conditions. We also sequenced four M. africanum isolates and compared their whole genomes with the published M. tuberculosis H37Rv genome. M. africanum strains have several non-synonymous SNPs or frameshift mutations in genes that were previously associated with growth-attenuation. M. africanum strains also have a higher mutation frequency in genes crucial for transport of sulphur, ions and lipids/fatty acids across the cell membrane into the bacterial cell. Surprisingly, 5 of 7 operons, recently described as essential for intracellular survival of H37Rv in the host macrophage, showed at least one non-synonymously mutated gene in M. africanum.
CONCLUSIONS/SIGNIFICANCE: The altered growth behaviour of M. africanum might indicate a different survival strategy within host cells.
西非的人类肺结核（TB）不仅由结核分枝杆菌引起，还由非洲分枝杆菌的两个谱系的细菌引起。例如，在冈比亚，40%的结核病是由感染非洲分枝杆菌西非 2 型引起的。这种细菌谱系与 HIV 感染、ESAT-6 免疫原性降低以及向活动性疾病的进展速度较慢有关。尽管这些特征表明非洲分枝杆菌的表型减弱，但尚未描述潜在的机制。自 1969 年文献中首次描述非洲分枝杆菌以来，固体培养基上非洲分枝杆菌的阳性培养时间比结核分枝杆菌的阳性培养时间长。然而，非洲分枝杆菌的生长延迟，这可能与宿主中较弱的毒力表型相关，以前尚未进行详细研究。
方法/主要发现：我们比较了来自冈比亚的结核分枝杆菌和非洲分枝杆菌分离株在两种液体培养系统中的生长速率。非洲分枝杆菌的生长速度明显比结核分枝杆菌慢，不仅是直接从痰液中生长时如此，而且在实验室条件下进行的生长实验中也是如此。我们还对四个非洲分枝杆菌分离株进行了测序，并将其全基因组与已发表的结核分枝杆菌 H37Rv 基因组进行了比较。非洲分枝杆菌菌株在以前与生长衰减相关的基因中存在几个非同义 SNP 或移码突变。非洲分枝杆菌菌株在对跨细胞膜进入细菌细胞的硫、离子和脂质/脂肪酸运输至关重要的基因中也具有更高的突变频率。令人惊讶的是，最近描述为 H37Rv 在宿主巨噬细胞中存活所必需的 7 个操纵子中的 5 个，在非洲分枝杆菌中至少有一个基因发生非同义突变。
结论/意义：非洲分枝杆菌生长行为的改变可能表明其在宿主细胞内的生存策略不同。
