Eshima Shintaro, Kurakado Sanae, Matsumoto Yasuhiko, Kudo Takayuki, Sugita Takashi
Department of Microbiology, Meiji Pharmaceutical University, Kiyose 204-8588, Tokyo, Japan.
Department of Pharmacy, Toshiba Rinkan Hospital, Sagamihara 252-0385, Kanagawa, Japan.
Microorganisms. 2022 Nov 3;10(11):2179. doi: 10.3390/microorganisms10112179.
Cross-kingdom multi-species biofilms consisting of fungi and bacteria are often resistant to antimicrobial treatment, leading to persistent infections. We evaluated whether the presence of Candida albicans affects the antibacterial tolerance of Escherichia coli in dual-species biofilms and explored the underlying mechanism. We found that the survival of E. coli in the presence of antibacterial drugs was higher in dual-species biofilms compared to single-species biofilms. This tolerance-inducing effect was observed in E. coli biofilms that were treated with a C. albicans culture supernatant. To explore the antibacterial tolerance-inducing factor contained in the culture supernatant and identify the tolerance mechanism, a heated supernatant, a supernatant treated with lyticase, DNase, and proteinase K, or a supernatant added to a drug efflux pump inhibitor were used. However, the tolerance-inducing activity was not lost, indicating the existence of some other mechanisms. Ultrafiltration revealed that the material responsible for tolerance-inducing activity was <10 kDa in size. This factor has not yet been identified and needs further studies to understand the mechanisms of action of this small molecule precisely. Nevertheless, we provide experimental evidence that Candida culture supernatant induces E. coli antibacterial tolerance in biofilms. These findings will guide the development of new treatments for dual-species biofilm infections.
由真菌和细菌组成的跨界多物种生物膜通常对抗菌治疗具有抗性，导致感染持续存在。我们评估了白色念珠菌的存在是否会影响双物种生物膜中大肠杆菌的抗菌耐受性，并探索其潜在机制。我们发现，与单物种生物膜相比，双物种生物膜中存在抗菌药物时大肠杆菌的存活率更高。在用白色念珠菌培养上清液处理的大肠杆菌生物膜中观察到了这种耐受性诱导效应。为了探索培养上清液中所含的抗菌耐受性诱导因子并确定耐受机制，使用了加热上清液、用溶菌酶、脱氧核糖核酸酶和蛋白酶K处理的上清液，或添加到药物外排泵抑制剂中的上清液。然而，耐受性诱导活性并未丧失，表明存在其他一些机制。超滤显示，负责耐受性诱导活性的物质大小<10 kDa。该因子尚未确定，需要进一步研究以精确了解这种小分子的作用机制。尽管如此，我们提供了实验证据，证明念珠菌培养上清液可诱导生物膜中大肠杆菌的抗菌耐受性。这些发现将指导双物种生物膜感染新治疗方法的开发。
