The Virulent Hypothetical Proteins: The Potential Drug Target Involved in Bacterial Pathogenesis

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 of 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 have been discussed.

Unveiling the mysteries: Functional insights into hypothetical proteins from Bacteroides fragilis 638R

“…The identification of these crucial genes opens avenues for targeted treatment approaches, advancing the management of B. fragilis infections [ 6 ]. However, a comprehensive understanding of the factors influencing B. fragilis 's unique pathogenicity is still lacking [ 9 ].…”

“…Hypothetical proteins (HPs) are proteins whose functions are not yet known. These proteins are often identified through genomic sequencing, but their roles in biological processes, virulence, and pathogenesis remains unclear [ 9 ]. Computational tools and techniques are used to analyze the physicochemical characteristics, protein-protein interactions, sub-cellular localization, functional classification, and antigenicity of these proteins, with a focus on their potential as drug targets [ 10 , 11 ].…”

Unraveling Coinfection Dynamics into 100 Whole Genome of Diarrheal Pathogens: A Genome-to-Systems Biology Approach withPlesiomonas shigelloides

“…In the realm of molecular biology and bioinformatics, a hypothetical protein is a protein that has been predicted to exist based on the presence of a corresponding gene in a genome or transcriptome, but for which there is limited or no experimental evidence to confirm its existence or function. In the case of bacteria, 25-50% of the genome comprises HPs, which may have roles in disease and therapeutic targets because they are involved in the pathogenesis of a disease or the regulation of a biological pathway [20]. Hypothetical proteins also have roles in microbial interactions by affecting the expression, regulation or function of other proteins in the host or the microbiome [21, 22].…”

“…Hypothetical proteins also have roles in microbial interactions by affecting the expression, regulation or function of other proteins in the host or the microbiome [21, 22]. Some methods to predict the function of hypothetical proteins using big data and machine learning are based on clustering the proteins based on their sequence similarity or interaction patterns [20, 22].…”