Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens

Abstract

During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection.

Keywords: adhesion; fimbriae; signal transduction; uropathogenic E. coli; virulence.

Figure 1

Adhesion regulates physiological responses in a variety of bacterial pathogens. (a) Adhesion of Neisseria meningitidis to host cells results in upregulation of pptB, posttranslational modification of pilin subunits, and dissemination of bacteria to enable colonization at distant sites. Figure reprinted with permission from Science [10]. (b) Type IV pili regulate adhesion-mediated signal transduction in Pseudomonas aeruginosa. One possible mechanism is that pilus retraction induces tension on the pili and changes the interaction between PilA and PilJ. Figure reprinted with permission from PNAS [13]. (c) Upon attachment to intestinal epithelial cells, enterotoxigenic E. coli exhibit broad changes in their gene expression profile leading to increased toxin production and changes in adhesion. One manifestation of the adherent transcriptional profile is the formation of surface blebs. Figure reprinted with permission from Infection and Immunity [15]. (d) Enterohemorrhagic Escherichia coli virulence factors, including Shiga toxins are, expressed from the locus of enterocyte effacement (LEE). Adhesion to HeLa cells induces LEE expression, which is further enhanced by fluid shear forces on par with those found in the intestinal tract.

Figure 1

Adhesion regulates physiological responses in a variety of bacterial pathogens. (a) Adhesion of Neisseria meningitidis to host cells results in upregulation of pptB, posttranslational modification of pilin subunits, and dissemination of bacteria to enable colonization at distant sites. Figure reprinted with permission from Science [10]. (b) Type IV pili regulate adhesion-mediated signal transduction in Pseudomonas aeruginosa. One possible mechanism is that pilus retraction induces tension on the pili and changes the interaction between PilA and PilJ. Figure reprinted with permission from PNAS [13]. (c) Upon attachment to intestinal epithelial cells, enterotoxigenic E. coli exhibit broad changes in their gene expression profile leading to increased toxin production and changes in adhesion. One manifestation of the adherent transcriptional profile is the formation of surface blebs. Figure reprinted with permission from Infection and Immunity [15]. (d) Enterohemorrhagic Escherichia coli virulence factors, including Shiga toxins are, expressed from the locus of enterocyte effacement (LEE). Adhesion to HeLa cells induces LEE expression, which is further enhanced by fluid shear forces on par with those found in the intestinal tract.

Figure 2

Adhesion-mediated signal transduction in E. coli. Adhesion of curli-expressing K-12 E. coli to polystyrene particles induces a surface-associated decrease in respiration. Cells constitutively expressing GFP were labeled with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) to monitor respiration (red stain). Shown are cells in suspension (left) or on the surface of a 25-µm particle (middle and right). Figure reprinted with permission from PLOS One [47].