Every person knows or has heard about antibiotics at some point in their life. In layman’s language we can say anything which is against life, But is it really? When I was a kid I used to think that antibiotics are something which will help me to get read of my infection, and now when I am grown up I have learned that antibiotics are compounds that are antimicrobial in nature. In a recent study, it has been revealed that antibiotics not only kill microbes like bacteria but also help to fight against diseases that are autoimmune in nature. So the question is how antibiotics that are designed to treat bacterial infections help to treat something related to the immune system. In this blog, I will try to show how amazingly a group of researchers showed that linezolid helps to fight against autoimmune diseases

What are autoimmune diseases?

Our body has certain cells called immune cells which protect us against any foreign harmful organisms. When these cells start fighting against their own self cells it is known as autoimmunity. Example rheumatoid arthritis.

What is linezolid?

Linezolid is a synthetic class of oxazolidinone antibiotics that inhibits bacterial protein synthesis by binding to the ribosomal subunits of the 30S and 50S. It works mainly against gram positive bacteria and multiple antibiotic resistant bacteria like Staphylococcus aureus and multidrug-resistant tuberculosis (MDR-TB).

Fig: linezolid structure
Fig: linezolid structure

Why linezolid work against mammalian (host) mitochondria?

The protein machinery of mitochondria and bacteria share similarities because it is known that mitochondria were originated from prokaryotes. If antibiotics like linezolid are penetrated or transported into mitochondria the mitochondrial translation gets inhibited by occupying the 50s ribosome which results in occupation of the peptidyl transferase center.

How the researchers proved mitochondrial translation inhibition by linezolid?

In order to prove mitochondrial translation inhibition by linezolid, the researchers labelled mitochondrial translation products with 32S methionine in murine lymphoma T cell line. They observed that there was no incorporation of 32S methionine in ETC subunits(encoded by mitochondrial DNA)

Fig: Electron transport chain producing NAD+ from NADH
Fig: Electron transport chain producing NAD+ from NADH

How mitochondrial translation inhibition lead to immunosuppression (against autoimmunity) by linezolid?

The Electron Transport Chain is composed of five subunits that are present in the inner membrane of the mitochondria. The ETC subunits are coded by both mitochondrial and nuclear DNA. When T cells get activated it leads to multiple cell division which requires translation of mitochondrial protein. The researchers observed that linezolid depleted mtDNA encoded mitochondrial-NADH-ubiquinone oxidoreductase chain (ND1) and cytochrome c oxidase 1(COX1) proteins in Th17 cells and CD4+ T cells. This results in reduced nicotinamide adenine dinucleotide concentration because of incomplete ETC assembly and thereby the cytokines released by Th17 cells i.e IL17 are reduced which plays a crucial role in autoimmune disease.

Conclusion

Thus antibiotics like linezolid can be used sometimes for immunosuppression and treat autoimmunity. But it has been observed that since linezolid leads to a reduction in  IL17 and IL17 is also responsible to fight against certain fungal and gram negative bacteria, further research need to be done in this area in order to observe if there are some underlining infections associated with such antibiotics for a safer approach.

Reference 

Almeida, L., Dhillon-LaBrooy, A., Castro, C.N., Adossa, N., Carriche, G.M., Guderian, M., Lippens, S., Dennerlein, S., Hesse, C., Lambrecht, B.N. and Berod, L., 2020. Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis. Immunity.

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