Caenorhabditis elegans mounts a p38 MAPK pathway-mediated defence to Cutibacterium acnes infection

Xiaowen Huang, Wen Pan, Wooseong Kim, Alexis White, Silei Li, Huiying Li, Kiho Lee, Beth Burgwyn Fuchs, Kang Zeng, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Cutibacterium acnes is capable of inducing inflammation in acne and can lead to a chronic prostatic infection. The diverse pathogenicity among different strains of C. acnes has been presented, but simple appropriate animal models for the evaluation of this bacterium are lacking. In this study, the nematode Caenorhabditis elegans was used as an invertebrate infection model. We revealed that C. acnes type strain ATCC 6919 caused lethal infections to C. elegans in 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 different C. acnes strains killed worms with a p value of less than.0001 when provided to C. elegans at 4.8 × 108 CFU/ml. The infection model was also employed to explore host defence responses. An increase in numerous immune effectors in response to C. acnes was detected. We focused on nine C-type lectins, including: clec-13, clec-17, clec-47, clec-52, clec-60, clec-61, clec-70, clec-71 and clec-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 of C. acnes infection. By monitoring the survival of mutant worms, we found that PMK-1, SEK-1 (MAPKK) and TIR-1 (MAPKKK) were critical in responding to C. acnes infection. C. elegans pmk-1 and tir-1 mutants exhibited higher mortality to C. acnes infection (p <.0001). In conclusion, C. elegans serves as a simple and valuable model to study C. acnes virulence and facilitates improvements in understanding of host innate immune responses.

Original languageEnglish
Article numbere13234
JournalCellular Microbiology
Volume22
Issue number10
DOIs
StatePublished - 1 Oct 2020

Keywords

  • C-type lectins
  • Caenorhabditis elegans
  • Cutibacterium acnes
  • immune defence
  • infection model
  • p38 MAPK pathway

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