Shayan Ahmed, Jamia Millia Islamia, New Delhi
Antibiotic resistance happens to be an important phenomenon emerging as a defence mechanism in bacteria. Antibiotic resistance mechanisms are the reason bacteria are able to counter the effects of antibiotics. Immeasurable and indiscriminate use of antibiotics ever since their discovery has contributed to the development of antibiotic resistance. This further compromises the potential treatment of life-threatening bacterial infections via the application of antibiotics. The development of antibiotic resistance is now a serious global concern due to the considerate increase in associated rates of global morbidity and mortality. Therefore, it becomes the utmost priority for researchers to develop novel strategies to combat antibiotic resistance. The native state mass spectrometry is one such strategy that has been recently established at Miami University in Ohio.
Combination drug therapy (inhibitor therapy) is an important technique for combating antibiotic resistance. In combination drug therapy, an antibiotic is coupled with an inhibitor and is prescribed to the patient infected with antibiotic-resistant bacterial strains. Antibiotic therapy Augmentin, i.e., antibiotic amoxicillin coupled with inhibitor clavulanic acid is one example of a combination drug therapy. Inhibitors deactivate the essential proteins that bacteria employ to develop antibiotic resistance. When the key protein in bacteria associated with antibiotic resistance is disabled, the antibiotic acts on its target, and thus the infection is treated.
Antibiotic-resistant microorganisms are tested using native state mass spectrometry to see how possible inhibitors operate. It is important to understand the complete action mechanism of the inhibitor molecule, before bringing it to clinical use. The bacterial protein metallo-beta-lactamase was studied by the research team at Miami University. Many clinical strains of bacteria are found resistant to all penicillin-like drugs because of this protein. Penicillin-like antibiotics account for more than 60% of the total antibiotic drugs that are used to treat bacterial infections.
The mechanism of action of certain inhibitors for the metallo-beta-lactamase was studied using native state mass spectrometry. The metallo-beta-lactamase contains two metal ions, this helped the investigators to study them using a number of spectroscopic methods. These tests provide further information about how the inhibitor works against the bacterial protein and if it may be used in clinical trials in the future.
A number of potential inhibitors were reported using native state mass spectrometry. Among these reported inhibitors, some operate by eliminating a component of the metallo-beta-lactamase that is necessary for its function. In humans, these inhibitors may also result in serious side effects. Some other inhibitors are also known, these bind to the metallo-beta-lactamase directly and inactivate the protein. The latter inhibitors are ideal for any novel inhibitor that may be employed for clinical purposes.
Also read: SETD2 in histone and tubulin methylation
Source: New technique allows for identification of potential drugs to fight resistant bacteria (2021, June 20) retrieved 21 June 2021 from https://phys.org/news/2021-06-technique-identification-potentialdrugs-resistant.html
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About Author: Shayan Ahmed is currently pursuing a Master of Science degree in Microbiology from the Department of Biosciences, Jamia Millia Islamia, New Delhi. His area of research interest lies in antibiotic resistance and associated molecular mechanisms. His recent work was focused on understanding colistin resistance patterns in the environment, particularly in water bodies.
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