Department of Biology, Integrative Science and Engineering Center, University of Dayton, Dayton, OH 45469, USA.
Toxins (Basel). 2020 Mar 30;12(4):218. doi: 10.3390/toxins12040218.
is a foodborne pathogen capable of secreting listeriolysin O (LLO), a pore-forming toxin encoded by the gene. While the functions of LLO have been studied extensively, how the production of LLO is modulated by the intestinal environment, devoid of oxygen and enriched in short chain fatty acids (SCFAs), is not completely understood. Using strain 10403s, we found that transcription was moderately decreased by aerobic SCFA exposures but significantly increased by anaerobic SCFA exposures. Moreover, aerobic, but not anaerobic, exposure to low levels of SCFAs resulted in a significantly higher LLO activity. These results demonstrated that transcriptional and post-transcriptional regulations of LLO production were separately modulated by SCFAs and were responsive to oxygen levels. Examining isogenic mutants revealed that PrfA and SigB play a role in regulating LLO production in response to SCFAs. Effects of SCFAs were also present in the cardiotropic strain 07PF0776 but distinctly different from those in strain 10403s. For both strains, prior exposures to SCFAs altered intracellular infections in Caco-2 and RAW264.7 cells and the plaque sizes in L fibroblasts, a result confirming the ability of to adapt to SCFAs in ways that impact its subsequent infection outcomes.
李斯特菌是一种食源性病原体，能够分泌李斯特菌溶血素 O（LLO），这是一种由 基因编码的孔形成毒素。虽然 LLO 的功能已被广泛研究，但它的产生如何被富含短链脂肪酸（SCFAs）且缺氧的肠道环境所调节，还不完全清楚。使用 10403s 株，我们发现有氧 SCFA 暴露会适度降低 转录，但无氧 SCFA 暴露会显著增加 转录。此外，有氧而非无氧暴露于低水平的 SCFAs 会导致 LLO 活性显著增加。这些结果表明，LLO 产生的转录和转录后调节分别受到 SCFAs 和氧气水平的调节。对同基因突变株的研究表明，PrfA 和 SigB 在响应 SCFAs 调节 LLO 产生方面发挥作用。SCFAs 的作用也存在于亲心肌毒性株 07PF0776 中，但与 10403s 株的作用明显不同。对于这两种菌株，SCFAs 的预先暴露改变了 Caco-2 和 RAW264.7 细胞中的细胞内感染和 L 成纤维细胞中的噬菌斑大小，这一结果证实了 能够以影响其后续感染结果的方式适应 SCFAs。
