Caenorhabditis elegansmounts a p38MAPKpathway-mediated defence toCutibacterium acnesinfection

Abstract

Cutibacterium acnesis capable of inducing inflammation in acne and can lead to a chronic prostatic infection. The diverse pathogenicity among different strains ofC. acneshas been presented, but simple appropriate animal models for the evaluation of this bacterium are lacking. In this study, the nematodeCaenorhabditis eleganswas used as an invertebrate infection model. We revealed thatC. acnestype strain ATCC 6919 caused lethal infections toC. elegansin solid and liquid culture media (p < .0001). Compared with the strain ATCC 6919, the antibiotic-resistant strain HM-513 was more virulent, resulting in reduced survival (p < .0001). Four differentC. acnesstrains killed worms with apvalue of less than .0001 when provided toC. elegansat 4.8 x 10(8) CFU/ml. The infection model was also employed to explore host defence responses. An increase in numerous immune effectors in response toC. acneswas detected. We focused on nine C-type lectins, including:clec-13,clec-17,clec-47,clec-52,clec-60,clec-61,clec-70,clec-71andclec-227. The induced expression of these C-type lectin genes was down-regulated in mutant worms deficient in the p38 mitogen-activated protein kinase (MAPK) pathway. Meanwhile, PMK-1 (MAPK) was phosphorylated and activated at the onset ofC. acnesinfection. By monitoring the survival of mutant worms, we found that PMK-1, SEK-1 (MAPKK) and TIR-1 (MAPKKK) were critical in responding toC. acnesinfection.C. elegans pmk-1andtir-1mutants exhibited higher mortality toC. acnesinfection (p < .0001). In conclusion,C. elegansserves as a simple and valuable model to studyC. acnesvirulence and facilitates improvements in understanding of host innate immune responses.