Rifampin resistance, Beijing-W clade-single nucleotide polymorphism cluster group 2 phylogeny, and the Rv2629 191-C allele in Mycobacterium tuberculosis strains.
Rifampin resistance is a key prognostic marker for treatment success in tuberculosis patients. Recently, Wang et al. demonstrated that Rv2629 A191C mutations were present in 99.1% of rifampin-resistant and 0% of rifampin-susceptible clinical Mycobacterium tuberculosis isolates and that overexpression of the Rv2629 191C allele in Mycobacterium smegmatis produced an eightfold increase in rifampin resistance. These results suggested that Rv2629 could be a cause of rifampin resistance and a valuable target for rifampin resistance detection assays. We developed a molecular-beacon assay to study the association between Rv2629 191 alleles and rifampin resistance in 246 geographically and phylogenetically diverse clinical M. tuberculosis isolates. The 191C allele was present in 30/98 (30.6%) rifampin-resistant isolates and 25/148 (16.9%) rifampin-susceptible isolates and was more common in isolates from Asia. Phylogenetic analysis demonstrated complete overlap between the 191C allele and single nucleotide polymorphism cluster group 2 (SCG-2), a phylogenetic lineage that corresponds to the Beijing-W clade of M. tuberculosis. All 55 (100%) 191C isolates were SCG-2, while none of the 191 191A isolates were SCG-2 (P < 0.001). No association was found between the 191C allele and rifampin resistance in an analysis that included the SCG type (P = 1.0). Also, in contrast to the findings of Wang et al., we found that overexpression of either Rv2629 191 allele in M. smegmatis did not produce an increase in rifampin resistance. We conclude that the Rv2629 191C allele is not associated with rifampin resistance and that the allele cannot be used as a molecular target to detect rifampin resistance. The allele appears to be an excellent marker for the Beijing-W clade/SCG-2 phylogenetic group.
Division of Infectious Disease, Department of Medicine, and the Ruy V. Lourenço Center for the Study of Emerging and Reemerging Pathogens, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Soumitesh
S
Chakravorty
Bola
B
Aladegbami
Alifiya S
AS
Motiwala
Yang
Y
Dai
Hassan
H
Safi
Michael
M
Brimacombe
Danica
D
Helb
David
D
Alland
D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D018628:Gene Dosage; D006801:Humans; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D012293:Rifampin / Q000494:pharmacology*; D014376:Tuberculosis / Q000382:microbiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C527629:Rv2629 protein, Mycobacterium; D012293:Rifampin