The development of antibiotics and therapeutics have been instrumental in the economic development that the world experiences today. Lifesaving therapeutics are threatened by the increasing prevalence of multi-drug resistant strains of bacteria, one of which includes Mycobacterium tuberculosis (MDR-TB).
A microscopic image of Mycobacterium tuberculosis. Credit: flickr . The first-line antibiotic treatments for tuberculosis are rifampicin and isoniazid. MDR-TB has shown resistance to these first-line therapeutics. Extensive drug resistant tuberculosis (XDR-TB) has demonstrated resistance to second-line therapeutics like fluoroquinolones and linezolid. According to the World Health Organization , multi-drug resistant tuberculosis or rifampicin-resistant tuberculosis reached a global prevalence of 206,030 cases in 2019. This is a 10% increase in prevalence from the previous 2018 year.
Inhibiting RNase HI Functionality Hinders the Transcription and Translation Mechanisms
With the effectiveness of first-line and second-line therapeutics in jeopardy, a study conducted by researchers at Cold Spring Harbor Laboratory suggest that the inhibition of the RNase HI enzyme could drive the extinction of these first and second-line resistant strains of TB. The study published in bioRxiv makes use of our Anti-DNA-RNA Hybrid [S9.6] Antibody , which helps detect R-loops as well as varying sizes of DNA-RNA hybrids. The antibody, as well as recombinant versions from our sister company Absolute Antibody, can be purchased on our website .
RNase HI is an enzyme necessary for maintaining genome stability in a bacterium. During translation RNase HI can resolve DNA supercoiling or uncoupling, and during transcription, DNA/RNA hybrids may form. This can cause R-loops to arise, which threatens bacteria’s genome stability. RNase HI can hydrolyze the RNA region to resolve the R-loops.
The structure of RNase HI is composed of RnhC and RnhA. One form of inhibition can arise when RnhC or RnhA is depleted, causing significant accumulation of R-loops and potentiate the activity of anti-tubular drugs. As a result, this saves first-line therapeutics like rifampicin and second-line medications from complete inefficiency.
The Future of Multi-Drug Resistant Mycobacterium Tuberculosis
The findings from this study provide a promising solution to MDR-TB. Targeting fundamental biochemical pathways like transcription and translation can become a reliable crutch in the makeup of MDR bacteria. There is still more research to be conducted in the inhibition of transcription or translation enzymes in other species of multi-drug resistant bacteria. This study provides promising results for this area of research. First-line and second-line therapeutics have successfully reduced cases of tuberculosis in the past. Their potentiation with RNase HI inhibition further amplifies the importance of the study’s findings.
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