Understanding the Effects of Metabolites and Trace Minerals on Microbes During Infection

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Background

Interactions between microbial pathogens and hosts are highly dynamic and influence the infection outcome. For instance, sensing of pathogens triggers metabolic reprogramming in host immune cells, such as increased glycolysis, to fuel inflammation, antimicrobial responses and phagocytic recruitment for microbial clearance. During this process, metabolites such as fatty acids, succinate and itaconate accumulate within immune cells prior to their release into the extracellular milieu. These metabolites shape the nature of the immune response by acting as signaling molecules.

Similarly, pathogens including the ESKAPE bacteria, fungi and parasites alter their metabolism to promote survival in different infection sites. Microbial metabolic flexibility, dictated by carbon catabolite repression, is one of many survival strategies. Other strategies include direct competition with host cells for metabolites or nutrients. Concurrently, these changes in microbial metabolic flux also impact the expression of virulence determinants. While metabolic competition between the pathogen and host cells is critical in determining the infection outcome, other factors that may influence these dynamics include the contribution of microbiota-derived metabolites or metabolites generated by co-infecting pathogens. Microbiome-derived metabolites such as short chain fatty acids and bile salts have been shown to regulate the function of key immune cells during infection with microbes.

The arms race between the host and pathogen is also exemplified at the level of nutritional immunity, whereby both compete for trace minerals such as iron, manganese and zinc. Host sequestration and utilization of these metals are vital given their role in the regulation of many metabolic and immune processes. Pathogens often adapt to conditions of mineral starvation by altering their metabolic preferences. Thus, changes in the metabolism of both host and pathogen during infection is likely to impact nutritional immunity and vice versa, an area that has thus far been neglected.

The goal of this Research Topic is to better understand the role of metabolites and metals in determining the outcome of infection. Given the rise in antimicrobial resistance and the lack of new therapeutic options, metabolic targets have become an alluring prospect for the future design of microbicidal therapies. Further research on host-pathogen metabolic interactions as well as additional factors which are likely to affect these dynamics is required before we can target host immunometabolism as an alternative and/or complementary therapeutic strategy to enhance the clearance of opportunistic microbial pathogens.

We invite researchers interested in host-pathogen interactions, immunometabolism and nutritional immunity to discuss how host-pathogen metabolic cross-talks and competition for trace minerals regulate both immune defenses and microbial infection. Submitted articles will focus on the various metabolic routes activated upon infection within both host and microbe, and how these influence adaptations of these organisms to the infected tissue. Authors will discuss how major mechanisms of microbial pathogenesis are impacted by host metabolic components or nutritional immunity.

We welcome the submission of Reviews, Mini-Reviews, Opinions as well as Original Research articles.

Keywords: Metabolic adaptation metabolites metals Immunometabolism Nutritional Immunity Host-pathogen interactions Microbes

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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