Molecular surveillance of antimicrobial resistance and transmission pattern of Mycobacterium leprae in Chinese leprosy patients

Abstract

Reports on antimicrobial resistance (AMR) of Mycobacterium leprae, relationship with bacteriological index (BI), and transmission in China are limited. We investigated the emergence of AMR mutations, the relationship between BI and AMR in complete, moderate and lack of BI decline cases, and molecular epidemiological features of AMR cases by enrolling 290 leprosy cases from four endemic provinces. Seven (2.41%), one (0.34%), five (1.72%), one (0.34%), and one (0.34%) strains had single mutations in folP1, rpoC, gyrA, gyrB, and 23S rRNA, respectively. Double mutations in folP1 and gyrA, rpoB and gyrA, and gyrA and 23S rRNA were observed in one (0.34%) strain each. Mutated strains occurred in three out of 81 (95% CI−0.005-0.079, p = 0.083) cases with complete BI decline, in seven out of 103 (95% CI 0.018-0.117, p = 0.008) cases with moderate BI decline, and in four out of 34 (95% CI 0.003-0.231, p = 0.044) cases with lack of BI decline. Most of these mutated strains were geographically separated and diverged genotypically. AMR mutations may not be the main cause of the lack of BI decline. The low transmission of AMR strains at the county level indicates an ongoing transmission at close contact levels.

A systematic review of Mycobacterium leprae DNA gyrase mutations and their impact on fluoroquinolone resistance

“…[13,25,26] The prior use of FQ was reported in 18 studies (Table 4). [13,[24][25][26]29,[32][33][34][35][36][37][38][39][40][41][42][43][44] Mutations in gyrA (Tables 1, 4) Among the 18 substitutions described in GyrA, nine were inside and seven outside the QRDR, and two were inside the intein (Table 1). The A91 substitution was the most prevalent.…”

“…Only five studies reported substitutions in GyrB, using PCR sequencing or WGS. [3,29,[42][43][44] Among the 755 strains studied for GyrB, only nine (1.2%) harbored substitutions corresponding to three amino acid changes. Among these, two were inside the QRDR (D464N, also named D205N by two authors, and T503I) [3,29,44] and one was outside (V214G) [29,43] (Table 4).…”

Reverse vaccinology and subtractive genomics approaches for identifying common therapeutics against Mycobacterium leprae and Mycobacterium lepromatosis

“…Because of this Rifampicin resistance, fluoroquinolones became the preferred category of second-line drugs. Unfortunately, the stains of M. leprae with quinolone-resistance have been reported in several countries [ 16 ]. This might be because of the wide use of quinolones for treating numerous types of infections.…”

Relapse in leprosy and drug resistance assessment in a tertiary hospital of the state of Espírito Santo, Brazil

“…In the present study, all cases assessed through molecular biology were negative for drug resistance, corroborating the absolute effectiveness of the therapeutic scheme proposed by the Brazilian Ministry of Health 4 . However, some studies have indicated drug resistance to rifampicin, dapsone, and ofloxacin, also in cases of leprosy recurrence 12 - 14 , in addition to reporting mutations other than the traditional ones, such as nth (DNA repair), rpo , rpoC (rifampicin), gyrB (ofloxacin), and 23s rRNA (clarithromycin), but still having uncertain roles 13 . Reja et al 14 and Chauffour et al 15 affirmed that even cases of negative bacilloscopy can be targets of drug resistance, deserving even more attention during the follow-up period.…”