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 H₂O₂ 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）是抗结核病治疗的基础，结核分枝杆菌（Mtb）耐药菌株的出现对我们在全球范围内控制结核病（TB）的能力构成重大威胁。编码过氧化氢酶KatG的基因突变赋予对高水平INH的抗性。在本文中，我们首次描述了先前在意大利完成了INH预防性治疗的HIV感染患者在意大利分离的Mtb临床菌株中包含katG基因的基因组区域的完全缺失。我们对Mtb菌株进行了基因型鉴定，结果表明katG缺失赋予了对INH的高水平抗性（MIC> 25.6μg/ mL）。这由于与野生型Mtb菌株相比，我们没有检测到对H ₂ O _2的敏感性增加，也没有在体外感染模型中损害其生长，因此katG缺失对Mtb的适应性没有显着影响。这些发现凸显了Mtb在保持健康和致病潜力的同时获得对INH的抗性的能力。