Near Surface Swimming of Salmonella Typhimurium Explains Target-Site Selection and Cooperative Invasion

Abstract

Targeting of permissive entry sites is crucial for bacterial infection. The targeting mechanisms are incompletely understood. We have analyzed target-site selection by S . Typhimurium. This enteropathogenic bacterium employs adhesins (e.g. fim ) and the type III secretion system 1 (TTSS-1) for host cell binding, the triggering of ruffles and invasion. Typically, S . Typhimurium invasion is focused on a subset of cells and multiple bacteria invade via the same ruffle. It has remained unclear how this is achieved. We have studied target-site selection in tissue culture by time lapse microscopy, movement pattern analysis and modeling. Flagellar motility (but not chemotaxis) was required for reaching the host cell surface in vitro. Subsequently, physical forces trapped the pathogen for ∼1.5–3 s in “near surface swimming”. This increased the local pathogen density and facilitated “scanning” of the host surface topology. We observed transient TTSS-1 and fim -independent “stopping” and irreversible TTSS-1-mediated docking, in particular at sites of prominent topology, i.e. the base of rounded-up cells and membrane ruffles. Our data indicate that target site selection and the cooperative infection of membrane ruffles are attributable to near surface swimming. This mechanism might be of general importance for understanding infection by flagellated bacteria.

Bistable Expression of CsgD in Salmonella enterica Serovar Typhimurium Connects Virulence to Persistence

“…Recent evidence suggests that the SPI-1 T3SS and flagellummediated motility are required for targeting of permissive invasion sites on host cells (64) and that these systems are often coregulated (65). In our RNA-seq experiment, 28 genes coding for flagellar assembly and chemotaxis proteins were identified as being more highly expressed in planktonic cells (see Data Set S1 in the supplemental material).…”

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

“…This may be partially explained by the occurrence of filamentous bacteria. The internalization of Salmonella in nonphagocytic cells is a highly coordinated event, mediated by flagella, fimbriae, and the SPI-1-encoded type III secretion system (34). Nonmotile mutant salmonellae have been reported to display reduced invasiveness in epithelial cells (35).…”

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

“…However, given its relative importance and the scope of this review, the focus here will be on the T3SS1-dependent entry mechanism. T3SS1-dependent invasion is a process with several steps [19], some of them common to other invasion mechanisms, that includes (i) movement in the gut lumen by passive diffusion and active motility and chemotaxis; (ii) transient interactions with the mucosal surface; (iii) reversible binding to target cells via adhesins; (iv) irreversible T3SS1-mediated docking; (v) translocation of bacterial effectors through T3SS1; (vi) manipulation of the host cells by effectors leading to rapid appearance of membrane ruffles; (vi) host cell invasion with formation of spacious vacuoles. Figure 2 summarizes the role of T3SS1 effectors in this process.…”