Velasquez Isabela, Ricci Kyra, Milusich Eve, Tuthill Bryon F, Sauer Karin, Hernández-Gómez Obed, Hua Jessica
Department of Forest and Wildlife Ecology, University of Wisconsin-Madison, 1630 Linden Dr, Madison, WI, 53706, USA.
Department of Biological Sciences, Binghamton University, Binghamton, NY, 13902, USA.
Sci Rep. 2025 Jul 2;15(1):22596. doi: 10.1038/s41598-025-02930-y.
Diseases are emerging at unprecedented rates, prompting global efforts to understand factors shaping disease outcomes. Microbes associated with hosts and the environment influence disease by secreting antipathogenic metabolites, hindering pathogen success. However, antibiotic contamination and costs associated with microbial responses to antibiotics may reduce antipathogenic efficacy. We investigated how antibiotic tolerance influences the antipathogenic properties of metabolites produced by Pseudomonas aeruginosa using in vitro and in vivo experiments. We found that metabolites from antibiotic-non-tolerant P. aeruginosa strains retained their antipathogenic properties and inhibited the growth of Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen responsible for amphibian declines worldwide. In contrast, metabolites from P. aeruginosa strains that developed antibiotic tolerance promoted Bd growth and exacerbated infection severity. These patterns were consistent in vitro and in vivo. We also ran toxicological and small molecule analyses of microbial metabolites, and findings suggest the divergent experimental outcomes may stem from differences in metabolite toxicity and profiles between strains. These findings underscore the hidden consequences of interactions between microbial responses to environmental changes and pathogens on infectious disease dynamics and highlight the need to integrate environmental change and eco-evolutionary perspectives into disease research.
疾病正以前所未有的速度出现，促使全球努力了解影响疾病结果的因素。与宿主和环境相关的微生物通过分泌抗病原代谢物来影响疾病，从而阻碍病原体的成功。然而，抗生素污染以及微生物对抗生素反应的成本可能会降低抗病原功效。我们使用体外和体内实验研究了抗生素耐受性如何影响铜绿假单胞菌产生的代谢物的抗病原特性。我们发现，来自非抗生素耐受性铜绿假单胞菌菌株的代谢物保留了它们的抗病原特性，并抑制了蛙壶菌（Bd）的生长，蛙壶菌是一种导致全球两栖动物数量减少的两栖类真菌病原体。相比之下，产生抗生素耐受性的铜绿假单胞菌菌株的代谢物促进了蛙壶菌的生长并加剧了感染严重程度。这些模式在体外和体内都是一致的。我们还对微生物代谢物进行了毒理学和小分子分析，结果表明不同的实验结果可能源于菌株之间代谢物毒性和谱的差异。这些发现强调了微生物对环境变化的反应与病原体之间相互作用对传染病动态的潜在影响，并突出了将环境变化和生态进化观点纳入疾病研究的必要性。
