Molecular insight into Salmonella virulence
Salmonella enterica are motile, intracellular pathogens that employ multiple virulence factors including flagella to efficiently colonise the host. The flagellum and the injectisome are complex self-assembling nanomachines that function by exporting proteins into the host cell via the conserved type III secretion system. Although the downstream infectious consequences of this process have been thoroughly studied, the molecular details of protein secretion via the type III export apparatus remains largely obscure. Furthermore, the biosynthesis of the flagellum seems to be controlled by poorly understood complex regulatory mechanisms. The EU-funded SALMOVIR project was designed to shed light on the contribution of bacterial motility and type-III protein secretion in Salmonella virulence. The long-term plan was to decipher the molecular mechanisms underlying these virulence traits and develop novel antimicrobial therapies. As a first step, researchers determined the growth rate of individual flagella in real-time and developed a biophysical model that explains how flagella grow outside the cell in the absence of any conventional energy source. They also uncovered a novel swimming behaviour on cell surfaces, which greatly affected host cell invasion and virulence. The scientific team characterised gene regulatory networks involved in flagella synthesis and discovered a novel, flagellar-dependent factor, RflM that is implicated in the process. Furthermore, they discovered a flagella-specific integral membrane protein that facilitates the assembly of the core complex of the bacterial type III secretion system. This step is critical for the formation of the bacterial flagellum. Taken together, the elucidation of the assembly mechanisms and molecular function of the type III secretion system has unveiled novel determinants of Salmonella virulence. Apart from a detailed understanding of the interplay between the flagellar and virulence systems during infection, the findings of the study support the development of novel targeting strategies. The development of new anti-microbial treatments is of paramount importance given the increase in drug resistant bacteria.
Keywords
Salmonella, flagellum, injectisome, type III secretion system, SALMOVIR
