Journal of Food & Industrial Microbiology

Functional Prediction and Assignment of Clostridium botulinum Type A1 Operome: A Quest for Prioritizing Drug Targets

Abstract

Chellapandi P*, Roja B, Saranya S and Prathiviraj R

Clostridium botulinum strain Hall is capable of producing a potent botulinum neurotoxin type A1 that causes food-borne, infant, and wound botulism in humans. Antibiotics and botulinum antitoxin are viable options for controlling growth and preventing botulinum intoxication in humans. The limited information on its proteins with unknown functions (operome or hypothetical proteins) hinders the discovery of new drug targets. Therefore, we aimed to apply a combined bioinformatics approach with literature support for the functional prediction, assignment, and validation of its operome. Our functional annotation scheme was based on sequence motifs, conserved domains, structures, protein folds, and evolutionary relationships of its operome. The precise functions of the 521 HPs (293 known) were annotated of which 293 HPs were previously annotated and 228 HPs not annotated from its genome. The newly identified operome contributed to the diverse cellular and metabolic processes of this organism. The function of its operome was involved in amino acid metabolism and botulinum neurotoxin biosynthesis. As a result of this study, 13 new virulence proteins from its operome were identified and characterized for their structure function relationships. The functions of new metabolic and virulence proteins allow this organism to colonize and interact with the human gastrointestinal tract. This study provides a quest for new drugs and targets for the treatment of C. botulinum underlying diseases in humans.