title: Mechanisms of first-line antimicrobial resistance in multi-drug and extensively drug resistant strains of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa.
abstract: BACKGROUND
  In South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic.
  
  
  METHODS
  In an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium tuberculosis in the KwaZulu-Natal province.
  
  
  RESULTS
  Classical mutations were detected in the katG, inhA and embB genes associated with resistance to isoniazid and ethambutol. Diverse mutations were recorded in the multidrug resistant (MDR) and extensively drug resistant (XDR) isolates for the rpoB and pncA gene associated with resistance to rifampicin and pyrazinamide.
  
  
  CONCLUSIONS
  M.tuberculosis strains circulating in our setting display a combination of previously observed mutations, each mediating resistance to a different drug. The MDR and XDR TB isolates analysed in this study displayed classical mutations linked to INH and EMB resistance, whilst diverse mutations were linked to RIF and PZA resistance. The similarity of the XDR strains confirms reports of the clonality of the XDR epidemic. The successful dissemination of the drug resistant strains in the province underscores the need for rapid diagnostics to effectively diagnose drug resistance and guide treatment.
authors: Medical Microbiology and Infection Prevention and Control, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu-Natal, Durban, South Africa.
authors: Navisha
authors: N
authors: Dookie
authors: Medical Microbiology and Infection Prevention and Control, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu-Natal, Durban, South Africa.
authors: A Willem
authors: AW
authors: Sturm
authors: Medical Microbiology and Infection Prevention and Control, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu-Natal, Durban, South Africa. moodleyp@ukzn.ac.za.
authors: Prashini
authors: P
authors: Moodley
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D004977:Ethambutol / Q000494:pharmacology; D054908:Extensively Drug-Resistant Tuberculosis / Q000382:microbiology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics; D010430:Pentosyltransferases / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000494:pharmacology; D013019:South Africa / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011718:Pyrazinamide; D004977:Ethambutol; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; C540269:EmbB protein, Mycobacterium tuberculosis; D010430:Pentosyltransferases; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis; D007538:Isoniazid; D012293:Rifampin
keywords: Clonality; Drug-resistance; Extensively drug-resistant-TB; First-line drugs; Multi-drug resistant-TB