Microbial Quest for Food in vivo: "Nutritional virulence" as an emerging paradigm.

Department of Microbiology and Immunology, College of Medicine, University of Louisville, KY, 40202.
Cellular Microbiology (Impact Factor: 4.92). 03/2013; 15(6). DOI: 10.1111/cmi.12138
Source: PubMed


Microbial access to host nutrients is a fundamental aspect of infectious diseases. Pathogens face complex dynamic nutritional host microenvironments that change with increasing inflammation and local hypoxia. Since the host can actively limit microbial access to nutrient supply, pathogens have evolved various metabolic adaptations to successfully exploit available host nutrients for proliferation. Recent studies have unraveled an emerging paradigm that we propose to designate as "nutritional virulence". This paradigm is based on specific virulence mechanisms that target major host biosynthetic and degradation pathways (proteasomes, autophagy, and lysosomes) or nutrient-rich sources, such as glutathione, to enhance host supply of limiting nutrients, such as Cysteine. Although Cys is the most limiting cellular amino acid, it is a metabolically favorable source of carbon and energy for various pathogens that are auxotroph for Cys but utilize idiosyncratic nutritional virulence strategies to generate a gratuitous supply of host Cys. Therefore, proliferation of some intracellular pathogens is restricted by a host nutritional rheostat regulated by certain limiting amino acids, and pathogens have evolved idiosyncratic strategies to short circuit the host nutritional rheostat. Deciphering mechanisms of microbial "nutritional virulence" and metabolism in vivo will facilitate identification of novel microbial and host targets for treatment and prevention of infectious diseases. Host-pathogen synchronization of amino acid auxotrophy indicates that this nutritional synchronization has been a major driving force in the evolution of many intracellular bacterial pathogens.

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Available from: Yousef Abu Kwaik, Sep 19, 2014
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    • "Although this term is applied to the acquisition of amino acids and carbon sources , certain nutritional ions or metals that are essential for cellular growth and other metabolic processes could be considered as part of this paradigm . As one of the most fundamental aspects of infectious diseases is the microbial acquisition of nutrients in vivo , which positively impacts in virulence as well as antibiotic resistance ( Santic and Abu Kwaik , 2013 ) , we suggest that the process of iron acquisition systems used by pathogenic microorganisms may be considered in the concept of ' nutritional virulence . ' Iron ( Fe ) is an essential element for almost all cells , including most bacteria because it serves as a cofactor for metabolic processes , such as redox reactions , nucleic acid synthesis , and electron transfer ( Tanabe et al . "
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    • "host ' s cells ( Abu Kwaik and Bumann , 2013 ) . Also , the presence of pathogenicity island components might suggest the use of such modules to achieve colonization using a pathogen - like strategy . "
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    • "Remarkably, these two amino acids are two non-essential amino acids, thus implying that prototrophy in broth does not necessarily predict independence toward host amino acid source(s) during infection. Comparison of predicted nutrient utilization and biosynthetic pathways of a series of mammalian pathogens support the notion that most pathogens share the capability to simultaneously utilize multiple nitrogen and carbon sources (Abu Kwaik and Bumann, 2013; Steeb et al., 2013). Our ongoing studies indicate that Francisella also relies on several other host-derived amino acid sources to multiply inside infected macrophages (Gesbert et al., 2015, unpublished). "
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