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在 中，脂蛋白 NlpD 通过维持膜完整性来响应酸应激，调节巨噬细胞的抗性和毒力。

The lipoprotein NlpD in responds to acid stress and regulates macrophage resistance and virulence by maintaining membrane integrity.

机构信息

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University , Tianjin, China.

Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage , Tianjin, China.

出版信息

Virulence. 2021 Dec;12(1):415-429. doi: 10.1080/21505594.2020.1870336.

DOI:10.1080/21505594.2020.1870336
PMID:33459158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7834084/
Abstract

, an emerging opportunistic pathogen, is implicated in severe foodborne outbreak infections in premature and full-term infants. Generally, acid tolerance is vital for the pathogenesis of foodborne pathogens; however, its role in virulence remains largely unknown. To screen out acid-tolerance determinants from transposon mutants, anovel counterselection method using gentamicin and acid was developed. Using the counterselection method and growth assay, we screened several acid-sensitive mutants and found that  encodes an acid-resistance factor in .  Compared to the wild-type strain, the mutant exhibited attenuated virulence in a rat model. Using macrophage THP-1 cells and a pH probe, we verified that enables bacteria to resist macrophages by resisting acidification. Finally, we confirmed that maintains membrane integrity in acid using propidium iodide permeabilization assays via flow cytometry. Our results confirm that is a novel virulence factor that permits to survive under acid stress conditions. Considering that NlpD is a conserved lipoprotein located in the bacterial outer membrane, NlpD could be used as a target for drug development.

摘要

艰难梭菌是一种新兴的机会致病菌，与早产儿和足月儿的严重食源性暴发感染有关。一般来说，耐酸性对于食源性病原体的发病机制至关重要；然而，其在 毒力中的作用在很大程度上仍然未知。为了从转座子突变体中筛选出耐酸决定因素，开发了一种使用庆大霉素和酸的新型反选择方法。使用反选择方法和生长测定，我们筛选了几个耐酸性敏感突变体，并发现 在 中编码一种酸抗性因子。与野生型菌株相比， 突变体在大鼠模型中表现出毒力减弱。使用巨噬细胞 THP-1 细胞和 pH 探针，我们验证了 使细菌能够通过抵抗酸化来抵抗巨噬细胞。最后，我们通过流式细胞术碘化丙啶渗透率测定证实 在酸性条件下保持 膜完整性。我们的研究结果证实 是一种新的毒力因子，使 能够在酸性应激条件下存活。鉴于 NlpD 是一种位于细菌外膜上的保守脂蛋白，NlpD 可以作为药物开发的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/dcc0e57852ba/KVIR_A_1870336_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/a2ffc95f087d/KVIR_A_1870336_F0001_B.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/a27cc0029096/KVIR_A_1870336_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/4c3305a73b29/KVIR_A_1870336_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/6490fb3c528f/KVIR_A_1870336_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/dcc0e57852ba/KVIR_A_1870336_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/a2ffc95f087d/KVIR_A_1870336_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/eaf5555c7f70/KVIR_A_1870336_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/0b272e489d24/KVIR_A_1870336_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/a27cc0029096/KVIR_A_1870336_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/4c3305a73b29/KVIR_A_1870336_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/6490fb3c528f/KVIR_A_1870336_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a669/7834084/dcc0e57852ba/KVIR_A_1870336_F0007_B.jpg

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