CCRI - St. Anna Children's Cancer Research Institute, Vienna, Austria.
Labdia - Labordiagnostik GmbH, Vienna, Austria.
Commun Biol. 2024 Nov 12;7(1):1496. doi: 10.1038/s42003-024-07145-x.
Polymicrobial co- and superinfections involving bacterial and fungal pathogens pose serious challenges for diagnosis and therapy, and are associated with elevated morbidity and mortality. However, the metabolic dynamics of bacterial-fungal interactions (BFI) and the resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus and the bacterium Klebsiella pneumoniae are clinically important pathogens sharing common niches in the human body, especially in the lower respiratory tract. We have exploited an integrated multi-omics approach to unravel the complex and multifaceted processes implicated in the interspecies communication involving these pathogens in mixed biofilms. In this setting, A. fumigatus responds to the bacterial challenge by rewiring its metabolism, attenuating the translational machineries, and by connecting secondary with primary metabolism, while K. pneumoniae maintains its central metabolism and translation activity. The flexibility in the metabolism of A. fumigatus and the ability to quickly adapt to the changing microenvironment mediated by the bacteria highlight new possibilities for studying the impact of cross-communication between competing interaction partners. The data underscore the complexity governing the dynamics underlying BFI, such as pronounced metabolic changes mounted in A. fumigatus interacting with K. pneumoniae. Our findings identify candidate biomarkers potentially exploitable for improved clinical management of BFI.
涉及细菌和真菌病原体的多微生物协同和超感染对诊断和治疗构成严重挑战，并与发病率和死亡率的升高有关。然而，细菌-真菌相互作用（BFI）的代谢动态及其对疾病结果的影响在很大程度上仍然未知。真菌烟曲霉和细菌肺炎克雷伯菌是临床上重要的病原体，它们在人体中具有共同的生态位，特别是在下呼吸道。我们利用集成的多组学方法来揭示涉及这些病原体在混合生物膜中相互作用的复杂和多方面的过程。在这种情况下，烟曲霉通过重新布线其代谢、减弱翻译机制以及将次级代谢与初级代谢连接起来，对细菌的挑战做出反应，而肺炎克雷伯菌则维持其中心代谢和翻译活性。烟曲霉代谢的灵活性以及通过细菌介导的快速适应不断变化的微环境的能力，为研究竞争相互作用伙伴之间交叉通讯的影响提供了新的可能性。这些数据强调了控制 BFI 动态的复杂性，例如与肺炎克雷伯菌相互作用的烟曲霉表现出明显的代谢变化。我们的研究结果确定了候选生物标志物，这些标志物可能可用于改善 BFI 的临床管理。
