{"doi":"10.3389/fcimb.2023.1276271","title":"Editorial: Understanding the effects of metabolites and trace minerals on microbes during infection","abstract":"Successful microbial pathogens establish infection and subvert the host immune response by utilizing their virulence determinants. Perhaps more importantly, the survival and replication of these pathogens within the microenvironments of infection sites depend on their ability to utilize alternative nutrient sources. This often involves the rewiring of metabolic pathways. Changes in microbial metabolic activities were historically used to identify microbial species by gold standard biochemical tests. However, over the last two decades, microbial metabolism has been neglected, particularly in favor of next generation sequencing.The emerging field of immunometabolism, the intersection between host cellular metabolism and immune function, has reignited interest in microbial metabolism. This is because the metabolic reprogramming of host cells not only alters immune responses but also the nutritional environment that supports microbial growth. Conversely, microbial metabolism affects immune cell function by depleting immunoregulatory metabolites. Outcomes of host-pathogen interactions are further affected by the diet and microbiota-derived metabolites, not only in the gut but also in distal organs. This Frontiers Research Topic highlights the metabolic cross-talk between the host and pathogen during infection, the factors that affect these dynamics, and their consequences on the infection outcome.Immunometabolism -Immunometabolism is an emerging concept that is central to both innate and adaptive immune regulation. The activation of specific metabolic pathways not only generates energy (ATP) but also dictates the function of immune cells (1). One prime example is the metabolic reprogramming which macrophages undergo following stimulation with the bacterial immunogen lipopolysaccharide (LPS) that fuels their pro-inflammatory signaling and microbicidal properties (1) (Figure 1 left panel). This involves switching from their basal metabolic state, mitochondrial oxidative phosphorylation (OXPHOS), to glycolysis. Several interruptions in the tricarboxylic acid (TCA) cycle are observed in LPS-stimulated macrophages, which result in the accumulation of the mitochondrial metabolites citrate, succinate, fumarate and itaconate and their export to the cytosol.Citrate is converted to acetyl-coA that is directed towards the production of inflammatory lipid-mediators such as prostaglandins (PGs) (2). Succinate stabilizes the transcription factor hypoxia-induced factor 1 alpha (HIF-1a), promoting glycolysis and the production of the proinflammatory cytokine IL-1b (3). Recently, fumarate was highlighted as a pro-inflammatory metabolite given its role in type I interferon (IFN) activation (4). Fumarate causes mitochondrial stress and damage, impairing respiration and releasing mitochondrial RNA (mtRNA), which induces the production of the cytokine IFNb. Thus, the above-mentioned metabolites polarize macrophages to a pro-inflammatory M1-like phenotype. Following inflammation, itaconate is produced in the mitochondrial matrix by the enzyme aconitate decarboxylase 1, Acod1 (also called Irg1). Itaconate exerts anti-inflammatory and anti-oxidative properties to restore homeostatic balance (5).In contrast, anti-inflammatory (M2-like) macrophages downregulate glycolysis and upregulate OXPHOS through catabolic pathways such as fatty acid oxidation (FAO) and glutaminolysis (6, 7) (Figure 1 right panel), which can also play a critical role in resolving infection. For example, recruitment of M2-like macrophages facilitates the transition into a postinflammatory resolution phase that is critical to resolving staphylococcal skin/soft tissue infections (8). Interestingly, it is increasingly being recognized that microbial pathogens can subvert immunometabolism to promote infection (9)(10)(11).profound metabolic stress on the host that can override the macrophage reprogramming associated with LPS or other pathogen-associated molecular patterns (PAMPs). For exampl","journal":"Frontiers in Cellular and Infection Microbiology","year":2023,"id":410982,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":692247,"name":"Andre Mu","orcid":"0000-0002-0853-9743","position":1,"is_corresponding":false},{"id":546748,"name":"Andrew J. Monteith","orcid":"0000-0002-7259-6574","position":2,"is_corresponding":false},{"id":246800,"name":"Tania Wong Fok Lung","orcid":"0000-0002-9318-9572","position":3,"is_corresponding":false},{"id":905057,"name":"Thomas Naderer","orcid":"0000-0003-2691-0283","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T01:21:38.940853Z","pmid":"37712062","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}