Abstract

Central Asian Strain 1 (CAS1) is the predominant Mycobacterium tuberculosis genotype in Pakistan. The occurrence of deletions in regions of differences (RDs) among CAS1 and other predominant genogroups in the country were investigated. Using stratified random sampling, 235 M. tuberculosis (185 pulmonary; 50 extrapulmonary) strains were selected from 926 previously spoligotyped isolates, including 171 CAS strains (133 CAS1 (ST26), 38 CAS subfamily), 8 Beijing isolates, 47 isolates belonging to other previously defined ("Other") clusters, and 9 previously undefined Unique isolates. Commonly reported RD deletions, RD1, RD750, RD207, RD149, RD152, RD105, RD150, RD142 and RD181, were investigated using a PCR-based method. Deletions in RDs 750, 149 and 152 were identified among CAS strains, and in RDs 207, 149, 152, 105, 150, 142 and 181 in Beijing isolates. CAS1 strains showed more frequent RD149 deletions compared with CAS subfamily strains (p = 0.036), and more frequent RD152 deletions compared with "Other" clusters (p = 0.003). RD149 and RD152 deletions were more frequent in Beijing isolates compared with CAS1 strains (p < 0.001). Concurrent RD149 and RD152 deletions were more frequent in CAS1 compared with "Other" clusters (p < 0.001) and in Beijing strains compared with CAS1 (p < 0.001). No significant difference was detected in RD deletion patterns between pulmonary and extra pulmonary isolates. Higher frequencies of RD149 and RD152 deletions and of concurrent RD149 and RD152 deletions were found in CAS1 and Beijing strains compared with CAS subfamilies, "Other" clusters and Unique strains. No association between these deletions and disease presentation, pulmonary or extrapulmonary tuberculosis, was observed.

Highlights

  • Central Asian Strain 1 (CAS1) is the predominant Mycobacterium tuberculosis genotype in Pakistan

  • It is recognized that variation in clinical M. tuberculosis strains are a result of repeated insertion or deletion events in specific genomic regions known as regions of differences (RDs) [3]

  • All the 38 CAS subfamily isolates were characterized by a RD750 deletion; 21.05% (n = 8) had RD149 deletions and 21.05% (n = 8) had RD152 deletions

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Summary

Introduction

Central Asian Strain 1 (CAS1) is the predominant Mycobacterium tuberculosis genotype in Pakistan. The occurrence of deletions in regions of differences (RDs) among CAS1 and other predominant genogroups in the country were investigated. Conclusion: Higher frequencies of RD149 and RD152 deletions and of concurrent RD149 and RD152 deletions were found in CAS1 and Beijing strains compared with CAS subfamilies, “Other” clusters and Unique strains. No association between these deletions and disease presentation, pulmonary or extrapulmonary tuberculosis, was observed. Molecular epidemiological studies have identified the predominance of Central Asian Strain 1 (CAS1) (39%) in this population, with Beijing strains constituting 3% of the Mycobacterium tuberculosis isolates from the country [2]. RD1 deletion, has been reported in M. tuberculosis strains from patients with active tuberculosis (TB) [8] and the significance of this deletion is yet to be established

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