State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou, China.
Front Cell Infect Microbiol. 2023 Jan 4;12:1056007. doi: 10.3389/fcimb.2022.1056007. eCollection 2022.
Infections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals. This pathogen has the potential to create adverse effects on human healthcare.
The MF GZ001 clinical strain was collected from the sputum of a 45-year-old male patient with a pulmonary infection. The morphological studies, comparative genomic analysis, and drug resistance profiles along with variants detection were performed in this study. In addition, comparative analysis of virulence genes led us to understand the pathogenicity of this organism.
Bacterial growth kinetics and morphology confirmed that MF GZ001 is a rapidly growing species with a rough morphotype. The MF GZ001 contains 6413573 bp genome size with 66.18 % high G+C content. MF GZ001 possesses a larger genome than other related mycobacteria and included 6156 protein-coding genes. Molecular phylogenetic tree, collinearity, and comparative genomic analysis suggested that MF GZ001 is a novel member of the M. fortuitum complex. We carried out the drug resistance profile analysis and found single nucleotide polymorphism (SNP) mutations in key drug resistance genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, blaF, thyA, embC, embR, and iniA. In addition, the MF GZ001strain contains mutations in iniA, iniC, pncA, and ribD which conferred resistance to isoniazid, ethambutol, pyrazinamide, and para-aminosalicylic acid respectively, which are not frequently observed in rapidly growing mycobacteria. A wide variety of predicted putative potential virulence genes were found in MF GZ001, most of which are shared with well-recognized mycobacterial species with high pathogenic profiles such as M. tuberculosis and M. abscessus.
Our identified novel features of a pathogenic member of the M. fortuitum complex will provide the foundation for further investigation of mycobacterial pathogenicity and effective treatment.
在全球范围内，非结核分枝杆菌引起的感染正在显著恶化。快速生长的致病物种 M. fortuitum 复合体对人类和动物的临床均具有重要意义。该病原体有可能对人类医疗保健产生不利影响。
从一名患有肺部感染的 45 岁男性患者的痰液中采集 MF GZ001 临床株。在这项研究中进行了形态学研究、比较基因组分析、耐药谱分析以及变异检测。此外，对毒力基因的比较分析使我们了解了该生物的致病性。
细菌生长动力学和形态学证实 MF GZ001 是一种快速生长的物种，具有粗糙的形态。MF GZ001 基因组大小为 6413573bp，GC 含量为 66.18%。MF GZ001 的基因组大于其他相关分枝杆菌，包含 6156 个编码蛋白的基因。分子系统发育树、共线性和比较基因组分析表明，MF GZ001 是 M. fortuitum 复合体的一个新成员。我们进行了耐药谱分析，发现 rpoB、katG、AAC(2')-Ib、gyrA、gyrB、embB、pncA、blaF、thyA、embC、embR 和 iniA 等关键耐药基因存在单核苷酸多态性（SNP）突变。此外，MF GZ001 菌株在 iniA、iniC、pncA 和 ribD 中存在突变，分别导致对异烟肼、乙胺丁醇、吡嗪酰胺和对氨基水杨酸的耐药性，这在快速生长的分枝杆菌中并不常见。在 MF GZ001 中发现了多种预测的潜在毒力基因，其中大多数与具有高致病性的公认分枝杆菌物种（如结核分枝杆菌和脓肿分枝杆菌）共享。
我们鉴定出 M. fortuitum 复合体的一种致病性成员的新特征，这将为进一步研究分枝杆菌的致病性和有效治疗提供基础。
