Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Department of Molecular Biology and Biochemistry, Bio21 Institute, University of Melbourne, Parkville, Australia.
PLoS Pathog. 2024 Aug 29;20(8):e1012440. doi: 10.1371/journal.ppat.1012440. eCollection 2024 Aug.
Reconstructing the evolutionary origins of Mycobacterium tuberculosis, the causative agent of human tuberculosis, has helped identify bacterial factors that have led to the tubercle bacillus becoming such a formidable human pathogen. Here we report the discovery and detailed characterization of an exceedingly slow growing mycobacterium that is closely related to M. tuberculosis for which we have proposed the species name Mycobacterium spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from a marine sponge, taken from the waters of the Great Barrier Reef in Queensland, Australia. Comparative genomics revealed that, after the opportunistic human pathogen Mycobacterium decipiens, M. spongiae is the most closely related species to the M. tuberculosis complex reported to date, with 80% shared average nucleotide identity and extensive conservation of key M. tuberculosis virulence factors, including intact ESX secretion systems and associated effectors. Proteomic and lipidomic analyses showed that these conserved systems are functional in FSD4b-SM, but that it also produces cell wall lipids not previously reported in mycobacteria. We investigated the virulence potential of FSD4b-SM in mice and found that, while the bacteria persist in lungs for 56 days after intranasal infection, no overt pathology was detected. The similarities with M. tuberculosis, together with its lack of virulence, motivated us to investigate the potential of FSD4b-SM as a vaccine strain and as a genetic donor of the ESX-1 genetic locus to improve BCG immunogenicity. However, neither of these approaches resulted in superior protection against M. tuberculosis challenge compared to BCG vaccination alone. The discovery of M. spongiae adds to our understanding of the emergence of the M. tuberculosis complex and it will be another useful resource to refine our understanding of the factors that shaped the evolution and pathogenesis of M. tuberculosis.
重建人类结核病病原体结核分枝杆菌的进化起源，有助于确定导致结核分枝杆菌成为如此强大的人类病原体的细菌因素。在这里，我们报告了一种极其缓慢生长的分枝杆菌的发现和详细特征，该细菌与结核分枝杆菌密切相关，我们提议将其命名为海绵分枝杆菌 sp. nov.（菌株 ID：FSD4b-SM）。该细菌是从澳大利亚昆士兰州大堡礁水域的一种海绵中分离出来的。比较基因组学显示，在机会性病原体分枝杆菌 M. decipiens 之后，M. spongiae 是迄今为止报道的与结核分枝杆菌复合体最密切相关的物种，其平均核苷酸同一性为 80%，并且关键结核分枝杆菌毒力因子广泛保守，包括完整的 ESX 分泌系统及其相关效应子。蛋白质组学和脂质组学分析表明，这些保守系统在 FSD4b-SM 中是功能性的，但它也产生了以前在分枝杆菌中未报道过的细胞壁脂质。我们研究了 FSD4b-SM 在小鼠中的毒力潜力，发现尽管细菌在鼻腔感染后 56 天仍存在于肺部，但未检测到明显的病理学。与结核分枝杆菌的相似性，以及其缺乏毒力，促使我们研究 FSD4b-SM 作为疫苗株的潜力，以及作为 ESX-1 基因座的遗传供体，以提高卡介苗的免疫原性。然而，与单独接种卡介苗相比，这两种方法都没有导致对结核分枝杆菌挑战的保护作用更优越。海绵分枝杆菌的发现增加了我们对结核分枝杆菌复合体出现的理解，它将成为另一个有用的资源，以完善我们对塑造结核分枝杆菌进化和发病机制的因素的理解。
