Drug resistance profiles and related gene mutations in slow-growing non-tuberculous mycobacteria isolated in regional tuberculosis reference laboratories of Iran: a three year cross-sectional study

ABSTRACT

There are limited studies on the antibiotic resistance patterns of slowly growing mycobacteria (SGM) species and their related gene mutations in Iran. This study aimed to elucidate the antibiotic susceptibility profiles and the mutations in some genes that are associated with the antibiotic resistance among SGM isolates from Iran. The SGM strains were isolated from sputum samples of suspected tuberculosis (TB) patients. SGM species were identified by standard phenotypic tests and were assigned to species level by amplification and sequencing of the dnaK gene. The minimum inhibitory concentration (MIC) of eight antibiotics was determined using broth microdilution method. The mutations in rrl, rpoB, gyrA, and gyrB genes were investigated in clarithromycin, rifampin, and moxifloxacin resistant isolates using sequencing method. A total of 77 SGM isolates including 46 (59.7%) Mycobacterium kansasii, 21 (27.3%) Mycbacterium simiae, and 10 (13%) Mycobacterium avium complex (MAC) were detected. The amikacin and linezolid with the susceptibility rates of 97.4% and 1.3% were the most and the least effective antibiotics, respectively. All MAC and M. simiae isolates, and 32 (69.6%) M. kansasii strains had multiple-drug resistance (MDR) profiles. The rrl, rpoB, gyrA, and gyrB genes showed various mutations in resistant isolates. Although the current study showed an association among resistance to the clarithromycin, rifampin, and moxifloxacin with mutations in the relevant genes, further research using the whole-genome sequencing is needed to provide a clearer insight into the molecular origins of drug resistance in SGM isolates.

KEYWORDS:

• Antibiotic resistance
• nontuberculous mycobacteria
• mutations
• slowly growing mycobacteria
• Iran

Acknowledgments

This work was part of M. Sc. thesis for Sousan Akrami, which was approved in Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. The authors would like to thank Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, for providing financial support for this research.

Author contributions

Azar Dokht Khosravi: Supervision; Writing – review & editing of manuscript, Data validation

Mohammad Hashemzadeh: Conceptualization; Formal analysis; Resources

Sousan Akrami: Data curation; Investigation; Methodology; Validation; Writing – original draft.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability

All relevant data are within the manuscript.

Additional information

Funding

This work was supported by the research affairs of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran under Grant number [OG-9906].