Abstract

Hypothetical proteins (HPs) are non-predicted sequences that are identified only by open reading frames in sequenced genomes, but their protein products remain uncharacterized by any experimental means. The genome of every species consists of HPs that are involved in various cellular processes and signaling pathways. Annotation of HPs is important as they play a key role in disease mechanisms, drug designing, vaccine production, antibiotic production, and host adaptation. In the case of bacteria, 25-50% of the genome comprises HPs, which are involved in metabolic pathways and pathogenesis. The characterization of bacterial HPs helps to identify virulent proteins that are involved in pathogenesis. This can be done using in-silico studies, which provide sequence analogs, physiochemical properties, cellular or subcellular localization, structure and function validation, and protein-protein interactions. The most diverse types of virulent proteins are exotoxins, endotoxins, and adherent virulent factors that are encoded by virulent genes present on the chromosomal DNA of the bacteria. This review evaluates virulent HPs of pathogenic bacteria, such as Staphylococcus aureus, Chlamydia trachomatis, Fusobacterium nucleatum, and Yersinia pestis. The potential of these HPs as a drug target in bacteria-caused infectious diseases, along with the mode of action and treatment approaches, has been discussed.

Keywords: Hypothetical proteins, pathogenesis, virulence, bacteria, viruses, drug.

Graphical Abstract