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As synthetic fungicides face increasing regulatory and resistance challenges, applying microbial biological control agents (MBCAs) presents a potential alternative crop-protection strategy. However, the chemical and toxicological consequences of such applications remain poorly understood. Using the model ascomycete\n                      <jats:italic toggle=\"yes\">Aspergillus nidulans<\/jats:italic>\n                      , the response to confrontations with twelve microbial partners, including bacterial and fungal MBCAs, plant pathogens, and phylloplane isolates was studied. Dual-culture assays revealed distinct interaction patterns, and transcriptome profiling showed confrontation-specific activation of secondary metabolite biosynthetic gene clusters (SMBGCs), with up to 50 SMBGCs differentially expressed in\n                      <jats:italic toggle=\"yes\">A. nidulans<\/jats:italic>\n                      . Complementary untargeted LC-MS\/MS identified hundreds of unique secondary metabolites (SMs), including compounds structurally resembling synthetic fungicides, including azoles and piperidines. Notably, cytotoxicity assays using human HEK-293 and HCT-116 cell lines revealed that SM mixtures from confrontations of\n                      <jats:italic toggle=\"yes\">A. nidulans<\/jats:italic>\n                      with\n                      <jats:italic toggle=\"yes\">Bacillus subtilis<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">Trichothecium roseum<\/jats:italic>\n                      exhibited significant toxicity, with IC\u2085\u2080 values as low as 52 \u00b5g\/mL. These findings demonstrate that microbial confrontations can trigger the production of diverse and specific sets of SMs, including compounds representing potential human health risks. This study underscores the need for confrontation-informed toxicological assessments in MBCA regulation and highlights the importance of developing safer biocontrol strategies in agriculture.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        This study shows fundamental changes at the transcriptome and metabolome level in the ubiquitous fungus\n                        <jats:italic toggle=\"yes\">Aspergillus nidulans<\/jats:italic>\n                        confronting various microorganisms, including microbial biological control agents. Strong modulations of transcript abundances of genes belonging to secondary metabolism gene clusters correlated with the formation of a vast array of novel secondary metabolites. Compounds formed in some confrontations were toxic to human cells, questioning the consumer safety of applying microbial biological control agents.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.02180-25","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:17:28Z","timestamp":1776097048000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Confrontations between\n                    <i>Aspergillus nidulans<\/i>\n                    and microbial biocontrol agents cause differential regulation of secondary metabolism and synthesis of chemicals toxic to human kidney and colon cells"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-0425","authenticated-orcid":true,"given":"Bennet Rohan 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