Park Hyun-Eui, Shin Jeong-Ih, Kim Kyu-Min, Choi Jeong-Gyu, Anh Won Jun, Trinh Minh Phuong, Kang Kyeong-Min, Byun Jung-Hyun, Yoo Jung-Wan, Kang Hyung-Lyun, Baik Seung-Chul, Lee Woo-Kon, Jung Myunghwan, Shin Min-Kyoung
Department of Microbiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Department of Microbiology, College of Medicine, Gyeongsang National University, Jinju, Republic of Korea; Department of Convergence of Medical Science, Gyeongsang National University, Jinju, Republic of Korea.
Infect Genet Evol. 2025 Mar;128:105716. doi: 10.1016/j.meegid.2025.105716. Epub 2025 Jan 19.
Mycobacterium avium complex (MAC) is an emerging pathogen leading to public health concerns in developing and developed countries, particularly among immunocompromised individuals and patients with structural lung diseases. Current clinical guidelines recommend combination antibiotic therapy for treating MAC pulmonary disease (MAC-PD). However, the rising prevalence of antibiotic resistance poses significant challenges, including treatment failure and clinical recurrence. A deeper understanding of the mechanisms underlying MAC antibiotic resistance is essential to improve treatment outcomes. This study investigates the genetic variations associated with aminoglycoside resistance in an antibiotic-induced Mycobacterium intracellulare mutant derived from a clinical strain. Whole-genome analysis identified seven mutations in the aminoglycoside-resistant mutant, including single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Key genetic alterations included a frameshift variant in a gene encoding a secreted protein antigen, missense mutations in rpsL and rsmG, and synonymous and in-frame deletion variants in srfAB and mtrB, respectively. These findings highlight the complex genetic landscape of aminoglycoside resistance in M. intracellulare. Understanding these resistance determinants provides valuable insights for developing diagnostic tools to detect drug-resistant MAC strains and optimizing therapeutic strategies for managing MAC infections in clinical practice.
鸟分枝杆菌复合群（MAC）是一种新出现的病原体，在发展中国家和发达国家都引发了公共卫生问题，尤其是在免疫功能低下的个体和患有结构性肺病的患者中。目前的临床指南推荐联合使用抗生素治疗MAC肺部疾病（MAC-PD）。然而，抗生素耐药性的日益普遍带来了重大挑战，包括治疗失败和临床复发。深入了解MAC抗生素耐药性的潜在机制对于改善治疗结果至关重要。本研究调查了一株源自临床菌株的抗生素诱导胞内分枝杆菌突变体中与氨基糖苷类耐药相关的基因变异。全基因组分析在氨基糖苷类耐药突变体中鉴定出七个突变，包括单核苷酸多态性（SNP）和插入/缺失（InDel）。关键的基因改变包括编码分泌蛋白抗原的基因中的移码变异、rpsL和rsmG中的错义突变，以及srfAB和mtrB中的同义及框内缺失变异。这些发现凸显了胞内分枝杆菌中氨基糖苷类耐药的复杂基因格局。了解这些耐药决定因素为开发检测耐药MAC菌株的诊断工具以及优化临床实践中管理MAC感染的治疗策略提供了有价值的见解。
