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分泌型抗原A肽聚糖水解酶对于细胞分离和免疫检查点抑制剂治疗的启动至关重要。

Secreted antigen A peptidoglycan hydrolase is essential for cell separation and priming of immune checkpoint inhibitor therapy.

作者信息

Klupt Steven, Fam Kyong Tkhe, Zhang Xing, Chodisetti Pavan Kumar, Mehmood Abeera, Boyd Tumara, Grotjahn Danielle, Park Donghyun, Hang Howard C

机构信息

Department of Immunology and Microbiology, Scripps Research, La Jolla, California 92037, United States.

Contributed equally.

出版信息

bioRxiv. 2024 Apr 12:2023.11.19.567738. doi: 10.1101/2023.11.19.567738.

DOI:10.1101/2023.11.19.567738
PMID:38014356
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10680833/
Abstract

is a microbiota species in humans that can modulate host immunity, but has also acquired antibiotic resistance and is a major cause of hospital-associated infections. Notably, diverse strains of produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity and immune checkpoint inhibitor antitumor activity. However, the functions of SagA in were unknown. Here we report that deletion of impaired growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, Δ showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, plasmid-based expression of SagA, but not its catalytically-inactive mutant, restored Δ growth, production of active muropeptides and NOD2 activation. SagA is therefore essential for growth, stress resistance and activation of host immunity.

摘要

是人类体内的一种微生物群物种，它可以调节宿主免疫力，但也获得了抗生素抗性，是医院相关感染的主要原因。值得注意的是，多种菌株会产生SagA，这是一种高度保守的肽聚糖水解酶，足以促进肠道免疫和免疫检查点抑制剂的抗肿瘤活性。然而，SagA在该菌中的功能尚不清楚。在此我们报告，该菌的缺失会损害其生长，并由于肽聚糖裂解和细胞分离缺陷导致肠球菌凸起和聚集。此外，缺失株显示出对抗生素的敏感性增加，活性胞壁肽水平降低，肽聚糖模式识别受体NOD2的激活减少，并且无法促进癌症免疫治疗。重要的是，基于质粒表达的SagA，而非其催化失活的突变体，恢复了缺失株的生长、活性胞壁肽的产生以及NOD2的激活。因此，SagA对于该菌的生长、抗逆性和宿主免疫激活至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/d76870a8266e/nihpp-2023.11.19.567738v4-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/adac8c14616a/nihpp-2023.11.19.567738v4-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/c8989cf0a906/nihpp-2023.11.19.567738v4-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/eeb3142478c1/nihpp-2023.11.19.567738v4-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/a4c5529a745c/nihpp-2023.11.19.567738v4-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/24757f760ddd/nihpp-2023.11.19.567738v4-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/0695e41b4db1/nihpp-2023.11.19.567738v4-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/aadcad120986/nihpp-2023.11.19.567738v4-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/25b9c77e6b09/nihpp-2023.11.19.567738v4-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/cc6f035d2790/nihpp-2023.11.19.567738v4-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/0eb7158281f3/nihpp-2023.11.19.567738v4-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/d76870a8266e/nihpp-2023.11.19.567738v4-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/adac8c14616a/nihpp-2023.11.19.567738v4-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/c8989cf0a906/nihpp-2023.11.19.567738v4-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/eeb3142478c1/nihpp-2023.11.19.567738v4-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/a4c5529a745c/nihpp-2023.11.19.567738v4-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/24757f760ddd/nihpp-2023.11.19.567738v4-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/0695e41b4db1/nihpp-2023.11.19.567738v4-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/aadcad120986/nihpp-2023.11.19.567738v4-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/25b9c77e6b09/nihpp-2023.11.19.567738v4-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/cc6f035d2790/nihpp-2023.11.19.567738v4-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/0eb7158281f3/nihpp-2023.11.19.567738v4-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5441/11017899/d76870a8266e/nihpp-2023.11.19.567738v4-f0004.jpg

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