The relationships of gene mutations between ESX and drug resistance in the patients with extra-pulmonary tuberculosis in local regions of Southwest China.

BACKGROUND

Drug resistant extrapulmonary tuberculosis (DR-EPTB) is a major threat to human health. The mycobacterial ESAT-6 secretion (ESX) system is main virulence protein export system of Mycobacterium tuberculosis (MTB). This study aimed to determine the relationships between ESX and drug resistance (DR) in patients with DR-EPTB in local regions of Southwest China.

METHODS AND DESIGN

Patients were retrospectively studied from January 2020 to December 2021. All the isolates were cultured, drug susceptibility was detected, and gene mutations were detected using whole-genome sequencing (WGS). The correlations between the mutant genes of the ESX system and DR pattern, patient demographics, and DR mutant gene sites were analyzed.

RESULTS

A total of 111 patients with DR-EPTB were enrolled including 40 females and 71 males. In the five ESX systems there were 1664 gene mutation sites and ESX-3 accounted for 32.6 %. The most common mutant gene site in all the ESX systems was eccC2. There was a significant difference in the number of mutant gene sites between ESX-1 and DR (P < 0.01). There were significant correlations between the numbers of mutant gene sites in the different ESX systems and gender (P < 0.05), age group (P < 0.05), residence (P < 0.01), type of treatment (P < 0.01), lineage (P < 0.01) and cluster (P < 0.01).

CONCLUSION

In patients with DR-EPTB, ESX-3 was the system that included the most mutant gene sites and the eccC2 gene had the highest frequency. The gender, age group, residence, type of treatment, lineage and cluster were risk factors for gene mutations in the ESX system. The mutant gene sites of ESX-1 were correlated with those of DR and the mutations in espA and espK may be the main factors.