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- Title
The Role of Nitroreductases in Resistance to Nitroimidazoles.
- Authors
Thomas, Carol; Gwenin, Christopher D.; Sanchis-Borja, Vincent
- Abstract
Simple Summary: Antimicrobial resistance continues to be a major global health threat. It is estimated by the WHO that 700,000 people die each year because of drug resistance, and this is predicted to rise to 10 million by 2050. As well as the increased cost, which is forecast to exceed $100 trillion, as more expensive drugs have to be deployed, illnesses often last longer and require hospital treatment. This, in turn, increases the strain on often-inadequate healthcare systems. As resistances continue to grow, finding alternatives is crucial. This review showed that nitroreductases play a role in drug activation but are also associated with resistance mechanisms. These mechanisms require further investigation to fully understand them before they can be utilised against multidrug-resistant organisms. This will depend on committed collaborations between the private and public sector to translate academic research into the clinic. Antimicrobial resistance is a major challenge facing modern medicine, with an estimated 700,000 people dying annually and a global cost in excess of $100 trillion. This has led to an increased need to develop new, effective treatments. This review focuses on nitroimidazoles, which have seen a resurgence in interest due to their broad spectrum of activity against anaerobic Gram-negative and Gram-positive bacteria. The role of nitroreductases is to activate the antimicrobial by reducing the nitro group. A decrease in the activity of nitroreductases is associated with resistance. This review will discuss the resistance mechanisms of different disease organisms, including Mycobacterium tuberculosis, Helicobacter pylori and Staphylococcus aureus, and how these impact the effectiveness of specific nitroimidazoles. Perspectives in the field of nitroimidazole drug development are also summarised.
- Subjects
NITROREDUCTASES; NITROIMIDAZOLES; HELICOBACTER pylori; DRUG activation; DRUG resistance in microorganisms; DRUG resistance; GRAM-negative anaerobic bacteria
- Publication
Biology (2079-7737), 2021, Vol 10, Issue 5, p388
- ISSN
2079-7737
- Publication type
Article
- DOI
10.3390/biology10050388