Bacterial Metabolism Shapes the Host-Pathogen Interface

Abstract

Bacterial pathogens have evolved to exploit humans as a rich source of nutrients to support survival and replication. The pathways of bacterial metabolism that permit successful colonization are surprisingly varied and highlight remarkable metabolic flexibility. The constraints and immune pressures of distinct niches within the human body set the stage for understanding the mechanisms by which bacteria acquire critical nutrients. In this article we discuss how different bacterial pathogens carry out carbon and energy metabolism in the host and how they obtain or use key nutrients for replication and immune evasion.

Figure 1. An simplified view of catabolic energy-yielding pathways in bacteria and points of relevance for the indicated bacterial pathogens

The figure shows a simplified outline of some of the different pathways for utilizing carbohydrates or fatty acids for the generation of ATP. These catabolic pathways and the anabolic pathways that they feed are under extremely complex levels of control, which have been studied mainly in non-infectious organisms (126). However, the unique metabolic strategies employed by infectious bacteria are becoming more appreciated as important aspects of bacterial pathogenesis (1). *ATP generated by substrate level phosphorylation; **ATP generated by oxidative phosphorylation; Solid lines: Metabolic Pathway; Dashed lines: Substrates that feed into catabolic pathways and products generated by bacteria as a result of metabolism or required for metabolism; Dotted lines: Main energy yielding metabolites generated from pathways. Blue letters indicate specific points of importance for the energy-yielding metabolism of select pathogens listed below (see Table 1 for summary): A. Pathogenic Streptococci (S. mutans, S. pyogenes, S. pneumoniae); B. Salmonella enterica serovar Typhimurium; C. Brucella abortus; D. Mycobacterium tuberculosis; E. Clostridium difficile; F. Enterohemorrhagic Escherichia coli (EHEC); G. Aggregatibacter actinomycetemcomitans; H. Listeria monocytogenes.

Figure 2. Graphical summary of bacterial mechanisms used to release intracellular host nutrients

Pathogenic bacteria perturb host cell functions to provide resources for survival and replication. Abbreviations: GSH (glutathione), GGT (γ-glutamyl transpeptidase), LCV (Legionella-containing vacuole), ER (endoplasmic reticulum), AA (amino acids), CERT (ceramide transfer protein), SM (sphingomyelin).