Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Cell Microbiol. 2020 Oct;22(10):e13234. doi: 10.1111/cmi.13234. Epub 2020 Jul 15.
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 × 10 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.
痤疮丙酸杆菌能够在痤疮中引发炎症，并可能导致慢性前列腺感染。不同痤疮丙酸杆菌菌株的多样性致病性已经得到了展示，但缺乏简单合适的动物模型来评估这种细菌。在这项研究中，秀丽隐杆线虫被用作无脊椎动物感染模型。我们揭示了痤疮丙酸杆菌标准株 ATCC 6919 在固体和液体培养基中对秀丽隐杆线虫造成致命感染（p < .0001）。与 ATCC 6919 菌株相比，抗生素抗性菌株 HM-513 具有更高的毒力，导致存活率降低（p < .0001）。当以 4.8 × 10 CFU/ml 的浓度将四种不同的痤疮丙酸杆菌菌株提供给秀丽隐杆线虫时，所有菌株均导致线虫死亡，p 值均小于.0001。该感染模型还被用于探索宿主防御反应。检测到大量免疫效应物对痤疮丙酸杆菌的反应增加。我们重点关注了 9 种 C 型凝集素，包括：clec-13、clec-17、clec-47、clec-52、clec-60、clec-61、clec-70、clec-71 和 clec-227。在缺乏 p38 丝裂原活化蛋白激酶（MAPK）途径的突变体蠕虫中，这些 C 型凝集素基因的诱导表达被下调。同时，PMK-1（MAPK）在痤疮丙酸杆菌感染开始时被磷酸化并激活。通过监测突变体蠕虫的存活率，我们发现 PMK-1、SEK-1（MAPKK）和 TIR-1（MAPKKK）在应对痤疮丙酸杆菌感染中至关重要。秀丽隐杆线虫 pmk-1 和 tir-1 突变体对线虫感染痤疮丙酸杆菌的死亡率更高（p < .0001）。总之，秀丽隐杆线虫是研究痤疮丙酸杆菌毒力的简单而有价值的模型，并有助于提高对宿主固有免疫反应的理解。
