Breaking down the microbiology world one bite at a time
The bacterial tug-of-war
“No pain, no gain” is a famous English saying that also applies to the bacterial community. While some bacterial infections are mild, severe infections require antibiotic treatments. Antibiotics are chemical compounds that treat bacterial diseases by either killing the bacteria or preventing their growth. Some commonly used antibiotics are amoxicillin, gentamicin, chloramphenicol, streptomycin, and azithromycin. Different antibiotics have different modes of action and target different bacterial components. However, the continuous use of these antibiotics against the bacterial species makes them resistant to these antibiotics, leading to the development of antibiotic resistance in bacteria. This phenomenon occurs when bacteria adapt and build defences against antibiotics, and antibiotics lose their ability to treat infections. For example, methicillin-resistant Staphylococcus aureus, multi-drug-resistant Mycobacterium tuberculosis, and erythromycin-resistant Bacillus subtilis are a few common antibiotic-resistant bacterial species.
A typical target for antibiotics is the ribosome, the protein-synthesizing factory of cells. They are a part of the “translational apparatus” and read the nucleotide sequence in messenger RNAs to link specific amino acids and form a protein. It has been noted in many studies (refer to additional sources) that antibiotic-resistant bacterial cells show a spontaneous emergence of altered ribosomes. However, the benefits of antibiotic resistance are not free of cost. The physiological cost of the development of variant ribosomes and antibiotic resistance in bacteria has been studied by E.C. Moon and his co-workers.
Moon and his team studied the L22* ribosome variant in B. subtilis, which arises due to a spontaneous mutation (change in the nucleic acid sequence of DNA and RNA) in the L22 ribosomal subunit. This mutation provides resistance against the antibiotic erythromycin. Magnesium ions (Mg2+) are key players in keeping the ribosome stable and working properly. Thanks to their small size and double positive charge, Mg2+ ions are especially important among all the other ions involved. The concentration of these Mg2+ ions plays a significant role in putting the different parts of the ribosome together, more so in the L22* variant. In addition to this, these ions also assist the bacteria against antibiotics that target ribosomes.
It is also important to take into notice the other roles of Mg2+ ions in the cell. One such role is pairing with ATP molecules, the energy currency of the cells, making Mg2+-ATP the most biologically active form of ATP molecules. ATP and ribosomes together use up most of the Mg2+ so they do not function up to their full potential during Mg2+ deficiency. Thus, when normal ribosomes (wild-type) mutate to the L22 variant, the bacteria become resistant to erythromycin, and their ribosomes and ATP molecules start competing for the limited magnesium supply. This, in turn, gives an advantage to bacteria with wild-type ribosomes, thereby making them targets for antibiotics. The effects of antibiotic resistance on the mutation in the L22 subunit and its effects on Mg2+ ions and ATP have been shown in the figures below.
This study shows that the concentration of Mg2+ ions in the bacterial cells with antibiotic resistance is an Achilles heel of the bacteria. The vulnerability of these bacteria to the concentration of Mg2+ ions can open doors to new treatments against antibiotic-resistant bacteria. This study has great significance in today’s world where antibiotic resistance causes millions of deaths around the globe every year and treating it has been a major challenge for the scientific community. Further insights into the intricate mechanisms of bacteria to find other such loopholes and to develop targeted treatments is the goal of the future.
Link to the original post: E.C. Moon, T. Modi, D.D. Lee, D. Yangaliev, J. Garcia-Ojalvo, S.B. Ozkan, G.M. Süel, Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria, Science Advances, 10(46), eadq5249, November 2024. DOI: 10.1126/sciadv.adq5249.
Featured image: Created by the author using Canva
Additional sources:
D. Criswell, V.L. Tobiason, J. S. Todmell, J.S. Lodmell, D.S. Samuels, Mutations conferring aminoglycoside and spectinomycin resistance in Borrelia burgdorferi, Antimicrobial Agents and Chemotherapy, 50(2), 445–452, February 2006. DOI: 10.118/AAC.50.2.445-452.2006.
R.A. Sharrock, T. Leighton, H.G. Wittmann, Macrolide and aminoglycoside antibiotic resistance mutations in the Bacillus subtilis ribosome resulting in temperature-sensitive sporulation, Molecular and General Genetics, 183(3), 538–543, November 1981. DOI: 10.1107/BF00268778.
S.H. Thorbjarnardóttir, R.Á. Magnúsdóttir, G. Eggertsson, S.A. Kagan, Ó.S. Andrésson, Mutations determining generalized resistance to aminoglycoside antibiotics in Escherichia coli, Molecular and General Genetics, 161(1), 89–98, April 1978. DOI: 10.1107/BF00266619.
P. Buckel, A. Buchberger, A. Böck, H.G. Wittmann, Alteration of ribosomal protein 6 in mutants of Escherichia coli resistant to gentamicin, Molecular and General Genetics, 158, 47–54, January 1977. DOI: 10.1107/BF00455118.
R. Nessar, J.M. Reyrat, A. Murray, B. Gicquel, Genetic analysis of new 16S rRNA mutations conferring aminoglycoside resistance in Mycobacterium abscessus, Journal of Antimicrobial Chemotherapy, 66(8), 1719–1724, August 2011. DOI: 10.1093/jac/dkr209.
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