Comparative study of enzymatic activities of new KatG mutants from low- and high-level isoniazid-resistant clinical isolates of Mycobacterium tuberculosis

Brossier, Florence; Boudinet, Marlène; Jarlier, Vincent; Pétrella, S.; Sougakoff, Wladimir

doi:10.1016/j.tube.2016.06.002

Cited by 19 publications

(19 citation statements)

References 57 publications

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“…20 Lack of clarity about the association between specific mutations, phenotypic resistance, and treatment outcomes hinders genotyping being used to make rapid treatment decisions. 21;22 inhA mutations are generally associated with lower phenotypic resistance than katG mutations, 23;24 but even within the same gene different mutations can cause differing levels of phenotypic resistance. For example, in vitro katG H270R mutations result in greater resistance levels than A162E.…”

Section: Resistance Mutationsmentioning

confidence: 99%

“…For example, in vitro katG H270R mutations result in greater resistance levels than A162E. 24 Beyond the role of single point mutations a strain’s genetic background contributes to the relationship between the genotype of resistance loci and phenotypic resistance, 25 as does the presence of compensatory mutations e.g. those in the ahpC gene.…”

Section: Resistance Mutationsmentioning

confidence: 99%

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Isoniazid-resistant tuberculosis: a cause for concern?

Stagg¹,

Lipman

McHugh³

et al. 2017

int j tuberc lung dis

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SUMMARY The drug isoniazid (INH) is a key component of global tuberculosis (TB) control programmes. It is estimated, however, that 16.1% of TB disease cases in Former Soviet Union countries and 7.5% of cases outside of those settings have non-multidrug resistant (MDR) INH resistance. Resistance has been linked to poorer treatment outcomes, post-treatment relapse and death, at least for specific sites of disease. Multiple genetic loci are associated with phenotypic resistance, but the relationship between genotype and phenotype is complex. This restricts the use of rapid sequencing techniques as part of the diagnostic process to determine the most appropriate treatment regimens for patients. The burden of resistance also influences the usefulness of INH preventative therapy (IPT). Despite seven decades of the use of INH our knowledge in key areas- such as the epidemiology of resistant strains, their clinical consequences, and their exact role in fuelling the MDR TB epidemic- is limited. The importance of non-MDR INH resistance needs to be re-evaluated both globally and by national TB control programmes.

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Section: Resistance Mutationsmentioning

confidence: 99%

Section: Resistance Mutationsmentioning

confidence: 99%

Isoniazid-resistant tuberculosis: a cause for concern?

Stagg¹,

Lipman

McHugh³

et al. 2017

int j tuberc lung dis

View full text Add to dashboard Cite

show abstract

“…[25] The S315T muta-tion decreases the catalase-peroxidase efficiency of the KatG enzymea nd INH activation. [61] The second mostc ommon mutation found occurs in the promoter region of inhA causing an overexpression of InhAo r, less frequently,amutation in InhA active site decreasing its affinity for the INH-NADH adduct. [36,39,59,60] It was observed that mutants associated with av ery highl evel of INH resistance generally also showed ad rastic decrease in catalase activity and in INH activation.…”

Section: Resistance To Inhmentioning

confidence: 99%

“…[36,39,59,60] It was observed that mutants associated with av ery highl evel of INH resistance generally also showed ad rastic decrease in catalase activity and in INH activation. [61] The second mostc ommon mutation found occurs in the promoter region of inhA causing an overexpression of InhAo r, less frequently,amutation in InhA active site decreasing its affinity for the INH-NADH adduct. [62][63][64] Moreover,m utations on the mabA gene resulted also in the upregulationo finhA.…”

Section: Resistance To Inhmentioning

confidence: 99%

Update of Antitubercular Prodrugs from a Molecular Perspective: Mechanisms of Action, Bioactivation Pathways, and Associated Resistance

2017

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The place of prodrugs in the current antitubercular therapeutic arsenal is preponderant, since two of the four first-line antitubercular agents, isoniazid (INH) and pyrazinamide (PZA), need to be activated by Mycobacterium tuberculosis before exerting their activity. In addition, six other prodrugs can be found in the second- and third-line therapeutic regimens. The emergence of mycobacterial strains resistant to one or several antitubercular agents is one of the main issues of the antitubercular therapy. In the case of prodrugs, the resistance phenomenon is often related to a mutation in the gene encoding for the activation enzymes, resulting thus in a default of these enzymes that are no more able to activate prodrugs. Consequently, identification of the prodrugs targets and a better understanding of their modes of action and also of their activation mechanisms are of crucial importance. Related to their molecular mechanism of activation, these prodrugs may thus be classified in four categories: activation via oxidation (catalase-peroxidase (KatG) or flavin monooxygenase (EthA) enzymes), condensation (FolP1 and FolC), hydrolysis (by the amidase PncA) and reduction (by the nitroreductase DnD) mechanisms. For each prodrug, these mechanisms are described in details, as well as the mechanism of action of its active metabolite. Finally, the reported resistance related to these mechanisms of activation/action are also addressed in a molecular perspective.

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“…towards humans [98], suggesting that this bifunctional KatG enzyme may have a specialized role in defense and virulence for bacterial species [70,97,98]. As a bifunctional catalase, KatG has been shown to interact with other substrates such as guaiacol [70], and in M. tuberculosis infection in mammals, it is able to inactivate the anti-tuberculosis drug isoniazid [99].…”

Section: Can Bacterial Antioxidant Activity Reduce Oxidative Stress Tmentioning

confidence: 99%

Reduction in Trace Element Mediated Oxidative Stress towards Cropped Plants via Beneficial Microbes in Irrigated Cropping Systems: A Review

2018

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Summer crops grown in Australia, including rice, cotton, and sugar cane, require high volumes of water, which is applied using irrigation systems. Yields from these crops are influenced by abiotic stressors. Fluctuations in the abiotic stressors, including soil pH and trace element availability, can increase levels of reactive oxygen species (ROS) in plants leading to increased oxidative stress and subsequent reduced crop growth and yield. One potential way of reducing plant ROS production and levels in these systems is through inoculation of these crops with beneficial microbes. The ability of beneficial microbes to enhance plant growth is well characterized, and it is also clear that many of them produce antioxidant enzymes. Presented in this review are the potential modes of action for microbes to reduce abiotic stress in cropped systems.

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Comparative study of enzymatic activities of new KatG mutants from low- and high-level isoniazid-resistant clinical isolates of Mycobacterium tuberculosis

Cited by 19 publications

References 57 publications

Isoniazid-resistant tuberculosis: a cause for concern?

Isoniazid-resistant tuberculosis: a cause for concern?

Update of Antitubercular Prodrugs from a Molecular Perspective: Mechanisms of Action, Bioactivation Pathways, and Associated Resistance

Reduction in Trace Element Mediated Oxidative Stress towards Cropped Plants via Beneficial Microbes in Irrigated Cropping Systems: A Review

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