Mechanism of Antibiotic Resistance by Protein Moonlighting

Abstract

Ikeanyibe Nneoma Collette74880*, Sabinus Oscar O. Eze74881, Tobechukwu Christian Ezike74882 and Kingsley Ozioma Omeje74883

Antibiotic resistance has become a major global health crisis, posing significant challenges in the treatment of bacterial infections. Most antibiotic resistance has emerged as a result of mutation or through the transfer of genetic material between microorganisms. Some studies on bacterial resistance have shown that there is a huge diversity of resistance mechanisms, with their distribution and interaction being mostly complex and unknown. However, various biochemical and physiological mechanisms are responsible for the development of antibiotic resistance. However, emerging evidence suggests that protein moonlighting, a phenomenon where a single protein can perform multiple functions in the cell beyond its originally described role, plays an important role in antibiotic resistance. Some proteins involved in the normal functioning of bacterial cells may have the ability to interact with antibiotics in ways that allow the bacteria to resist their effects. For example, Pyruvate Dehydrogenase (PDH), a key enzyme in energy metabolism, can bind to and detoxify fluoroquinolone antibiotics like ciprofloxacin. In Pseudomonas aeruginosa (P. aeruginosa), PDH sequesters the antibiotic within its active site, rendering it inactive. Additionally, some proteins involved in the transport of nutrients into the bacterial cell may also be able to transport antibiotics out of the cell, preventing them from accumulating to toxic for the bacteria. For example, ToIC an outer membrane protein found in Escherichia coli (E. coli) act as a channel for various molecules, including antibiotics. However, specific mutations in ToIC can alter its conformation, reducing the passage of certain antibiotics like cephalosporin’s and there by offering resistance. Other proteins may modify or degrade antibiotics within the cell, rendering them ineffective. For example the protein enolase, which is involved in glycolysis, has been shown to possess β-lactamase activity, allowing it to inactivate β lactam antibiotics. Overall, protein moonlighting is a complex phenomenon that can contribute to antibiotic resistance in a various ways. Understanding how these proteins function in bacterial cells and how they interact with antibiotics is an important area of research that could ultimately lead to the development of novel strategies for combating antibiotic-resistant bacteria.

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