Post-Translational Modifications: Host Defence Mechanism, Pathogenic Weapon, and Emerged Target of Anti-Infective Drugs

Post-translational modifications are changes introduced to proteins after their translation. They are the means to generate molecular diversity, expand protein function, control catalytic activity and trigger quick responses to a wide range of stimuli. Moreover, they regulate numerous biological processes, including pathogen invasion and host defence mechanisms. It is well established that bacteria and viruses utilize post-translational modifications on their own or their host’s proteins to advance their pathogenicity. Doing so, they evade immune responses, target signaling pathways and manipulate host cytoskeleton to achieve survival, replication and propagation. Many bacterial species secrete virulence factors into the host and mediate hostpathogen interactions by inducing post-translational modifications that subvert fundamental cellular processes. Viral pathogens also utilize post translational modifications in order to overcome the host defence mechanisms and hijack its cellular machinery for their replication and propagation. For example, many coronavirus proteins are modified to achieve host invasion, evasion of immune responses and utilization of the host translational machinery. PTMs are also considered potential targets for the development of novel therapeutics from natural products with antibiotic properties, like lasso peptides and lantibiotics. The last decade, significant progress was made in understanding the mechanisms that govern PTMs and mediate regulation of protein structure and function. This urges the identification of relevant molecular targets, the design of specific drugs and the discovery of PTM-based medicine. Therefore, PTMs emerge as a highly promising field for the investigation and discovery of new therapeutics for many infectious diseases.

Keywords: ADP-ribosylation, Antimicrobial drugs, Antiviral drugs, Bacterial effector proteins, Bioengineering, Biopharmaceuticals, Coronavirus, Deamidation, Drug target, Elimination, Glycosylation, Host invasion, Innate immunity, Lantibiotics, Lipidation, Natural antimicrobial peptides, Palmitoylation, Pathogenic bacteria, RiPPs, Secretion systems, Spike protein, Thiopeptides, Ubiquitination, Vaccine design.