ROJA B., THAMANNA L. AND CHELLAPANDI P.
Abstract
Clostridium botulinumtype A3 str. Loch Maree is a clinically important strain that producesbotulinum neurotoxin type A3 and causes foodborne, infant, and wound botulism worldwide. Studying themechanism underlying the virulence of this organism is imperative to understand its antibacterial resistanceand discovering new drugs or inhibitors. The biochemical and molecular characteristics of this organismhave been intensively studied, but their gene regulatory mechanisms are unclear. Hence, we reconstructedthe transcriptional regulatory network from the complete genome of this organism and analyzed interactivegenes from the identified hub module using a knowledge-based bottom-up approach. The biologicalreliability, topological properties, and robustness of the regulatory network model were validated withnetwork parameters, followed by gene ontology terms and literature support. The reconstructed regulatorynetwork consisted of 12 transcriptional regulators associated with 2369 coding genes. ResD, SpoOA, ComK,CcpC, DinR, DegU, CitT, CodY, GerE, GltC, GltR, IolR, and LevR were identified as transcriptionalregulators from this organism homologous to Bacillus subtilis 168. These regulators have been shown tocontrol beta-lactamase, methyl-accepting chemotaxis protein, DNA replication protein DnaD, sensorhistidine kinase, and putative membrane proteins of this organism. This study also predicted all possiblepromoter sites in regulated genes and their associated molecular functions. We conclude that a globalregulatory network model of this organism provides insights into its growth physiology and virulenceelicitation in the human intestinal environment.