+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Genomic sequence based scanning for drug resistance-associated mutations and evolutionary analysis of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis



Genomic sequence based scanning for drug resistance-associated mutations and evolutionary analysis of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis



Journal of Infection 65(5): 412-422



To better understand the molecular mechanisms and evolution of drug resistance in Mycobacterium tuberculosis (M. tuberculosis), we performed a genomic sequence based scanning of drug resistance-associated loci for multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains. Forty-five pairs of primers covering known drug resistance-associated loci compiled in the TBDReaMDB database were designed to perform the analysis of drug resistance-associated mutations for 14 M. tuberculosis clinical isolates from TB patients in China. Genetic diversity and evolutionary analysis was done using concatenated nucleotide sequences of drug resistance-associated loci. Forty-four types of mutations were identified in 14 M. tuberculosis clinical isolates. Average nucleotide diversity for drug resistance-associated loci increased in the M. tuberculosis isolates as the drug resistance increased (π = 0, π = 0.00021, and π = 0.00028 for susceptible, MDR, and XDR isolates, respectively). The dN/dS ratios for coding regions of drug resistance-associated genes in MDR and XDR isolates were 2.73 and 1.83, respectively. MDR and XDR isolates were distributed sporadically on different branches in the phylogenetic trees. Our study provides supporting evidence to demonstrate that the MDR- and XDR-M. tuberculosis strains have evolved independently driven by positive selection.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036461054

Download citation: RISBibTeXText

PMID: 22728171

DOI: 10.1016/j.jinf.2012.06.007


Related references

A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis. Memorias do Instituto Oswaldo Cruz 111(2): 93, 2016

Additional drug resistance in Mycobacterium tuberculosis isolates from resected cavities among patients with multidrug-resistant or extensively drug-resistant pulmonary tuberculosis. Clinical Infectious Diseases 54(6): E51-E54, 2012

Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment. Antimicrobial Agents and ChemoTherapy 53(8): 3353-3356, 2009

Beijing genotype of Mycobacterium tuberculosis is significantly associated with linezolid resistance in multidrug-resistant and extensively drug-resistant tuberculosis in China. International Journal of Antimicrobial Agents 43(3): 231-235, 2014

A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype. Molecular Genetics and Genomics 288(9): 425-436, 2013

Mutations in extensively drug-resistant Mycobacterium tuberculosis that do not code for known drug-resistance mechanisms. Journal of Infectious Diseases 201(6): 881-888, 2010

The emergence of extensively drug-resistant tuberculosis (TB): TB/HIV coinfection, multidrug-resistant TB and the resulting public health threat from extensively drug-resistant TB, globally and in Canada. Canadian Journal of Infectious Diseases and Medical Microbiology 18(5): 289-291, 2007

Multidrug-resistant tuberculosis in panama is driven by clonal expansion of a multidrug-resistant Mycobacterium tuberculosis strain related to the KZN extensively drug-resistant M. tuberculosis strain from South Africa. Journal of Clinical Microbiology 51(10): 3277-3285, 2013

RNA expression analysis of efflux pump genes in clinical isolates of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis in South Korea. Infection Genetics and Evolution 49: 111-115, 2017

Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea. Annals of Laboratory Medicine 38(6): 563-568, 2018

Scrutinizing the drug resistance mechanism of multi- and extensively-drug resistant Mycobacterium tuberculosis: mutations versus efflux pumps. Antimicrobial Resistance and Infection Control 8: 70, 2019

Pulmonary resection combined with isoniazid- and rifampin-based drug therapy for patients with multidrug-resistant and extensively drug-resistant tuberculosis. International Journal of Infectious Diseases 13(2): 170-175, 2008

Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis: epidemiology and control. Expert Review of Anti-Infective Therapy 5(5): 857-871, 2007

Inactivation of multidrug resistant (MDR)- and extensively drug resistant (XDR)-Mycobacterium tuberculosis by photodynamic therapy. Photodiagnosis and Photodynamic Therapy 10(4): 694-702, 2013

Transmission of extensively drug-resistant and multidrug resistant Mycobacterium tuberculosis in families identified by genotyping. Chinese Medical Journal 126(3): 521-525, 2013