Graduate Program in Life Sciences, Molecular Microbiology and Immunology Program, University of Maryland, Baltimore, Maryland, USA.
Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
Antimicrob Agents Chemother. 2017 Nov 22;61(12). doi: 10.1128/AAC.01573-17. Print 2017 Dec.
In microbial biofilms, microorganisms utilize secreted signaling chemical molecules to coordinate their collective behavior. Farnesol is a quorum sensing molecule secreted by the fungal species and shown to play a central physiological role during fungal biofilm growth. Our pervious and studies characterized an intricate interaction between and the bacterial pathogen , as these species coexist in biofilm. In this study, we aimed to investigate the impact of farnesol on survival, biofilm formation, and response to antimicrobials. The results demonstrated that in the presence of exogenously supplemented farnesol or farnesol secreted by in biofilm, exhibited significantly enhanced tolerance to antimicrobials. By using gene expression studies, mutant strains, and chemical inhibitors, the mechanism for the enhanced tolerance was attributed to upregulation of drug efflux pumps. Importantly, we showed that sequential exposure of to farnesol generated a phenotype of high resistance to antimicrobials. Based on the presence of intracellular reactive oxygen species upon farnesol exposure, we hypothesize that antimicrobial tolerance in may be mediated by farnesol-induced oxidative stress triggering the upregulation of efflux pumps, as part of a general stress response system. Hence, in mixed biofilms, may influence the pathogenicity of through acquisition of a drug-tolerant phenotype, with important therapeutic implications. Understanding interspecies signaling in polymicrobial biofilms and the specific drug resistance responses to secreted molecules may lead to the identification of novel targets for drug development.
在微生物生物膜中，微生物利用分泌的信号化学分子来协调其集体行为。法呢醇是一种由真菌物种分泌的群体感应分子，在真菌生物膜生长过程中发挥着核心生理作用。我们之前的 和 研究描述了 和细菌病原体 之间复杂的相互作用，因为这些物种在生物膜中共存。在这项研究中，我们旨在研究法呢醇对 的生存、生物膜形成和对抗生素的反应的影响。结果表明，在存在外源补充的法呢醇或生物膜中法呢醇分泌的情况下， 对抗生素的耐受性显著增强。通过使用基因表达研究、 突变株和化学抑制剂，增强耐受性的机制归因于药物外排泵的上调。重要的是，我们表明， 依次暴露于法呢醇会产生对抗生素高度耐药的表型。基于法呢醇暴露时细胞内活性氧物质的存在，我们假设 中的抗生素耐受性可能是由法呢醇诱导的氧化应激触发外排泵的上调介导的，作为一般应激反应系统的一部分。因此，在混合生物膜中， 通过获得耐药表型可能会影响 的致病性，这具有重要的治疗意义。了解多微生物生物膜中的种间信号传递以及对分泌分子的特定耐药反应可能会导致发现新的药物开发靶标。
