Triclosan Enhances the Clearing of Pathogenic Intracellular Salmonella or Candida albicans but Disturbs the Intestinal Microbiota through mTOR-Independent Autophagy

Chao Wang, Zhongyang Yu, Xiaochen Shi, Xudong Tang, Yang Wang, Xueyan Wang, Yanan An, Shulin Li, Yan Li, Xuefei Wang, Wenjing Luan, Zhaobin Chen, Mingyuan Liu, Lu Yu

Triclosan (TCS) is a broad-spectrum antimicrobial agent, whose well-known antibacterial mechanism is inhibiting lipid synthesis. Autophagy, an innate immune response, is an intracellular process that delivers the cargo including pathogens to lysosomes for degradation. In this study, we first demonstrated that TCS induced autophagy in a dose-dependent manner in non-phagocytic cells (HeLa) and in macrophages (Raw264.7) andin vivo. The western blot results also revealed that TCS induced autophagy via the AMPK/ULK1 and JNK/ERK/p38 pathways independent of mTOR. The immunofluorescence results indicated that TCS up-regulated the expression of the ubiquitin receptors NDP52 and p62 and strengthened the co-localization of these receptors withSalmonella entericaTyphimurium (S. typhimurium) orCandida albicans(C. albicans) in infected MΦ cells. In addition, sub-lethal concentrations of TCS enhanced the clearing of the pathogensS. typhimurium orC. albicansin infected MΦ and in corresponding mouse infection modelsin vivo. Specifically, we found that a sub-inhibitory concentration of TCS induced autophagy, leading to an imbalance of the intestinal microflora in mice through the analysis of 16s rRNA Sequencing. Together, these results demonstrated that TCS induced autophagy, which enhanced the killing against pathogenicS. typhimurium orC. albicanswithin mammal cells but broke the balance of the intestinal microflora.