Can mycobacterial katG genetic changes in isoniazid-resistant tuberculosis influence human disease features?

Patricio Escalante, R. McKean-Cowdin, S. V. Ramaswamy, Natalie Williams-Bouyer, L. D. Teeter, B. E. Jones, E. A. Graviss

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)644-651
Number of pages8
JournalInternational Journal of Tuberculosis and Lung Disease
Volume17
Issue number5
DOIs
StatePublished - May 1 2013

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Isoniazid
Tuberculosis
Mutation
Mycobacterium tuberculosis
Virulence Factors
Sputum
DNA Sequence Analysis
Case-Control Studies
Animal Models
Lung

Keywords

  • KatG protein
  • Mycobacterium tuberculosis
  • Resistance
  • Virulence

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Can mycobacterial katG genetic changes in isoniazid-resistant tuberculosis influence human disease features? / Escalante, Patricio; McKean-Cowdin, R.; Ramaswamy, S. V.; Williams-Bouyer, Natalie; Teeter, L. D.; Jones, B. E.; Graviss, E. A.

In: International Journal of Tuberculosis and Lung Disease, Vol. 17, No. 5, 01.05.2013, p. 644-651.

Research output: Contribution to journalArticle

Escalante, Patricio ; McKean-Cowdin, R. ; Ramaswamy, S. V. ; Williams-Bouyer, Natalie ; Teeter, L. D. ; Jones, B. E. ; Graviss, E. A. / Can mycobacterial katG genetic changes in isoniazid-resistant tuberculosis influence human disease features?. In: International Journal of Tuberculosis and Lung Disease. 2013 ; Vol. 17, No. 5. pp. 644-651.
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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.",
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N2 - 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.

AB - 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.

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