title: Can mycobacterial katG genetic changes in isoniazid-resistant tuberculosis influence human disease features?
abstract: BACKGROUND
  Isoniazid-resistant (INHr) Mycobacterium tuberculosis isolates often have katG mutations, and katG is a virulence factor in animal models. It is unclear if katG mutations or other mutations influence the characteristics of human disease.
  
  
  OBJECTIVE
  To determine if the presence of INHr-conferring mutations were associated with distinct clinical features of tuberculosis (TB).
  
  
  METHODS
  In a retrospective case-control study, INHr-conferring mutations were determined by DNA sequencing. We examined associations between clinical characteristics in patients with INHr M. tuberculosis (stratified by groups of relevant INHr-conferring mutations, including katG-S315T and inhA-C(-)15T mutations) and pan-susceptible (PS) isolates.
  
  
  RESULTS
  Twenty-nine INHr TB cases and 50 PS controls were evaluated. Disease characteristics were not statistically different between INHr and PS cases. However, patients infected with non-katG mutants were associated with a higher rate of sputum culture conversion at 1 month after adjustment for relevant covariates (adjusted OR [aOR] 4.4, 95%CI 1.1-23.6, P = 0.04). Patients infected with katG mutants were associated with a higher rate of unilateral disease (aOR 4.7, 95%CI 1.0-34.3, P = 0.05).
  
  
  CONCLUSIONS
  Most INHr TB cases with non-katG mutations have disease associated with faster response to treatment, and most cases with katG mutants have localized lung involvement.
authors: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. escalante.patricio@mayo.edu
authors: P
authors: P
authors: Escalante
authors: R
authors: R
authors: McKean-Cowdin
authors: S V
authors: SV
authors: Ramaswamy
authors: N
authors: N
authors: Williams-Bouyer
authors: L D
authors: LD
authors: Teeter
authors: B E
authors: BE
authors: Jones
authors: E A
authors: EA
authors: Graviss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D016017:Odds Ratio; D010641:Phenotype; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D014774:Virulence; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D007538:Isoniazid