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Since the discovery of penicillin by Alexander Fleming in 1928, scientists have sought ways to effectively combat bacteria. Antibiotics, a class of drugs capable of destroying bacteria or slowing down their growth, are the results of that quest. Although several approaches to developing antibiotics have been taken, harnessing the bacteria genes to produce lethal antibiotic substances against other bacteria is by far the most recent. Due to the numerous opportunities genes hold, scientists agree that this approach may also hold the key to the development of a wide variety of antibiotics that would effectively subserve the antimicrobial functions intended. Contrary to what one may expect, however, this approach is not only complex but presents some major difficulties and one of the most difficult questions scientists have asked is, “How can silent genes be harnessed for antibiotic synthesis?” Researchers at Rice University may have answered that question and thus unraveled a rare gem in the field of genetics and biology.
Harnessing Hidden Bacterial Genes. Credit: Andrea Ameruoso
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What are silent genes?
Silent genes are inactive DNA sequences that are generally not expressed or expressed to a very low extent. In bacteria, such as streptomyces used in the production of active antibiotic metabolites, the inactivity of these genes greatly limits the antibiotics obtained from the organisms as these genes are only activated in nature under certain conditions. In this study, however, the scientists designed a novel switch that can “turn on” and “turn off” these genes anytime.
Activating and deactivating silent genes
The study was performed on Streptomyces, a genus of bacteria consisting of about 500 species. They observed that aside from the usually expressed genes, each of these species has a myriad of silent genes that on activation can produce antibiotic molecules. To unlock these genes, scientists developed customized CRISPR-Cas9 tools aimed at controlling the expression of these genes. As observed, the CRISPR technology adapted to the bacterial immune system mechanisms, and using this, it located specific genes along the DNA strand used. This greatly simplified access to the gene clusters initially hidden. About 40 of these clusters were discovered in each streptomyces strain, representing 40 different new molecules derivable from each strain.
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Clinical significance
Each of these 40 molecules represents a potential antibiotic with lethal effects against bacteria. With many bacteria such as Acinetobacter, Pseudomonas, and various Enterobacteriaceae (like E. coli and Klebsiella) becoming resistant to already existing antibiotics, there is a need to develop even more to replace them. Interestingly, this study explores DNA sequences that have not been explored before and thus the molecules produced may posess even greater antibiotic potential than the ones already known. Additionally, the scientists postulate that the molecules discovered may also possess antifungal and anticancer effects, thus advancing the field of chemotherapy generally.
Conclusion
Although CRISPR-Cas9 technologies have been used in previous studies to activate genes in Escherichia coli, this research is the first of its kind to explore the possibilities of harnessing the antimicrobial propensities of silent genes in streptomyces. It represents a milestone achievement that aside from increasing the number of antibiotics currently known would also create a template for the exploration of silent genes in other microorganisms which may hold secrets beyond human imagination.
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References
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