Infection and Drug Resistance (Sep 2021)
Genetic Diversity and Drug Susceptibility Profiles of Multidrug-Resistant Tuberculosis Strains in Southeast China
Abstract
Shufang Lin,1 Shuzhen Wei,1 Yong Zhao,1 Zhisong Dai,1 Jian Lin,1 Yu Pang2 1Fujian Provincial Key Laboratory of Zoonosis Research, Fujian Center for Disease Control and Prevention, Fuzhou, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of ChinaCorrespondence: Shuzhen WeiFujian Center for Disease Control and Prevention, Fuzhou, People’s Republic of ChinaTel/Fax +86 591 8343 1464Email [email protected] PangBeijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel/Fax +86 10 8950 9359Email [email protected]: Multidrug-resistant tuberculosis (MDR-TB) isolates collected from Fujian province, China were assessed for molecular epidemiological characteristics. Analysis of isolate genotype profiles revealed that the Beijing genotype was associated with especially high drug resistance and community transmission rates.Methods: A total of 119 MDR-TB isolates obtained from TB patients in Fujian province were typed using 24–locus mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and spoligotyping. Drug susceptibility testing of all isolates was conducted using the L-J proportion method, with pyrazinamide (PZA) susceptibility testing conducted using the Mycobacterium Growth Indicator Tube System 960 (MGIT 960).Results: We obtained 26 spoligotypes for the 119 isolates examined in this work. Spoligotyping results revealed that 80 (67.2%) isolates possessed the Beijing family genotypic profiles. Patients aged 25– 44 years and ≥ 45 years were most likely to be infected by non-Beijing genotypes. The percentage of clustered cases with both PZA and ofloxacin (OFLX) resistance was significantly greater than the corresponding percentage for non-clustered cases. Of 44 PZA-resistant isolates, 28 isolates (63.6%) harbored pncA mutations, while pncA mutations were only detected in 7 (9.3%) PZA-susceptible isolates.Conclusion: Our data demonstrate that the Beijing genotype is the dominant lineage among MDR-TB strains circulating in Fujian. Thus, MDR-TB infections occurring within this province are not likely associated with recent transmission events. PZA and fluoroquinolone resistance profiles were found to be associated with clustered isolates. Mutation of pncA is the main driver of MDR-TB PZA resistance and is associated with mutation sites scattered throughout the entire pncA protein-coding region.Keywords: multidrug resistance, Mycobacterium tuberculosis, genotype, pyrazinamide, pncA
