Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis

Abstract

It is interesting to speculate that the evolutionary drive for microbes to develop pathogenic characteristics was to access the nutrient resources that animals provided. Animal environments that pathogens colonize have likely driven the evolution of new bacterial characteristics to maximize these new nutritional opportunities. This review focuses on genomic and functional aspects of pathogen metabolism that allow efficient utilization of nutrient resources provided by animals. Similar to genes encoding specific virulence traits, genes encoding metabolic functions have been horizontally acquired by pathogens to provide a selective advantage in host tissues. Selective advantage in host tissues can also be gained by loss of function mutations that alter metabolic capabilities. Greater understanding of bacterial metabolism within host tissues should be important for increased understanding of host-pathogen interactions and the development of future therapeutic strategies.

Figure 1

Acquisition of virulence factors along with metabolic capabilities allows bacteria to thrive in a new environment.

Figure 2

Interplay between bacterial metabolism and virulence pathways in two intestinal pathogens. The sialic acid utilization promotes V. cholerae colonization of the intestinal tract [33]. The Vibrio pathogenicity island VPI2 is exclusively found in toxinogenic strains. It contains genes encoding a neuraminidase and proteins necessary for transport and catabolism of sialic acids. The neuraminidase converts host cell surface polysialogangliosides to GM1 mono-ganglioside, the cholera toxin specific receptor, resulting in release of sialic acid. This reaction not only provides an energy source (sialic acid) to V. cholerae but also promotes the binding of cholera toxin to host intestinal epithelial cells [33, 34]. Tetrathionate respiration promotes S. Typhimurium colonization of the intestinal tract. Highly toxic hydrogen sulphide (H₂S) produced by colonic bacteria is converted to less toxic thiosulphate (S₂O₃²⁻) by caecal mucosa. Thiosulphate can be oxidized into tetrathionate (S₄O₆²⁻) by nitric oxide radicals and reactive oxygen species produced by the gut in response to S. Typhimurium pathogenesis [27]. Thiosulphate selectively inhibits coliforms [28] but allows Salmonella to utilize ethanolamine or 1,2-propanediol as carbon sources for anaerobic growth in the lumen [29].