Mycobacterium avium complex (MAC) is a group of slow-growing mycobacteria that includes Mycobacterium avium and Mycobacterium intracellulare. MAC pulmonary disease (MAC-PD) poses a threat to immunocompromised individuals and those with structural pulmonary diseases worldwide. The standard treatment regimen for MAC-PD includes a macrolide in combination with rifampicin and ethambutol. However, the treatment failure and disease recurrence rates after successful treatment remain high. In the present study, we investigated the unique characteristics of small colony variants (SCVs) isolated from patients with MAC-PD. Furthermore, revertant (RVT) phenotype, emerged from the SCVs after prolonged incubation on 7H10 agar. We observed that SCVs exhibited slower growth rates than wild-type (WT) strains but had higher minimum inhibitory concentrations (MICs) against multiple antibiotics. However, some antibiotics showed low MICs for the WT, SCVs, and RVT phenotypes. Additionally, the genotypes were identical among SCVs, WT, and RVT. Based on the MIC data, we conducted time-kill kinetic experiments using various antibiotic combinations. The response to antibiotics varied among the phenotypes, with RVT being the most susceptible, WT showing intermediate susceptibility, and SCVs displaying the lowest susceptibility. In conclusion, the emergence of the SCVs phenotype represents a survival strategy adopted by MAC to adapt to hostile environments and persist during infection within the host. Additionally, combining the current drugs in the treatment regimen with additional drugs that promote the conversion of SCVs to RVT may offer a promising strategy to improve the clinical outcomes of patients with refractory MAC-PD.

中文翻译：

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较小菌落带来更大问题：MAC 肺病患者中出现鸟分枝杆菌复合体的抗生素耐受性小菌落变种

鸟分枝杆菌复合体（MAC）是一组生长缓慢的分枝杆菌，包括鸟分枝杆菌和胞内分枝杆菌。MAC 肺病 (MAC-PD) 对全世界免疫功能低下者和结构性肺病患者构成威胁。MAC-PD 的标准治疗方案包括大环内酯类药物联合利福平和乙胺丁醇。然而，治疗失败和成功治疗后的疾病复发率仍然很高。在本研究中，我们研究了从 MAC-PD 患者中分离出的小集落变异体 (SCV) 的独特特征。此外，在 7H10 琼脂上长时间孵育后，SCV 出现了回复突变 (RVT) 表型。我们观察到，SCV 的生长速度比野生型 (WT) 菌株慢，但对多种抗生素的最低抑制浓度 (MIC) 较高。然而，一些抗生素对 WT、SCV 和 RVT 表型显示出较低的 MIC。此外，SCV、WT 和 RVT 的基因型相同。根据 MIC 数据，我们使用各种抗生素组合进行了时间杀灭动力学实验。不同表型对抗生素的反应各不相同，RVT 最敏感，WT 表现出中等敏感性，SCV 表现出最低敏感性。总之，SCV表型的出现代表了MAC为适应恶劣环境并在宿主感染期间持续存在而采取的生存策略。此外，将治疗方案中的现有药物与促进 SCV 转化为 RVT 的其他药物相结合，可能会提供一种有前景的策略，以改善难治性 MAC-PD 患者的临床结果。