Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy; Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie - Sezione di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy; Dipartimento di Sicurezza e Bioetica, Sez. Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
Int J Med Microbiol. 2021 May;311(4):151506. doi: 10.1016/j.ijmm.2021.151506. Epub 2021 Apr 19.
Isoniazid (INH) is the cornerstone of the anti-tuberculosis regimens and emergence of Mycobacterium tuberculosis (Mtb) resistant strains is a major threat to our ability to control tuberculosis (TB) at global level. Mutations in the gene coding the catalase KatG confer resistance to high level of INH. In this paper, we describe for the first time a complete deletion of the genomic region containing the katG gene in an Mtb clinical strain isolated in Italy in a patient with HIV infection that previously completed INH preventive therapy. We genotypically characterized the Mtb strain and showed that katG deletion confers high-level resistance to INH (MIC > 25.6 μg/mL). The katG deletion did not impact significantly on Mtb fitness as we did not detect enhanced susceptibility to HO compared to the wild type Mtb strains nor impaired growth in in vitro infection models. These findings highlight the ability of Mtb to acquire resistance to INH while maintaining fitness and pathogenic potential.
异烟肼（INH）是抗结核方案的基石，结核分枝杆菌（Mtb）耐药菌株的出现是我们在全球范围内控制结核病（TB）能力的主要威胁。编码过氧化氢酶 KatG 的基因发生突变可赋予 INH 高水平耐药性。本文首次描述了在一名 HIV 感染患者中分离的意大利临床结核分枝杆菌菌株中，katG 基因所在的基因组区域完全缺失，该患者曾完成 INH 预防性治疗。我们对结核分枝杆菌菌株进行了基因分型特征描述，并表明 katG 缺失赋予 INH 高水平耐药性（MIC > 25.6μg/ml）。katG 缺失并没有显著影响结核分枝杆菌的适应性，因为与野生型结核分枝杆菌菌株相比，我们没有检测到对 HO 的敏感性增强，也没有在体外感染模型中观察到生长受损。这些发现强调了结核分枝杆菌在保持适应性和致病性的同时获得 INH 耐药性的能力。
