The serine protease HtrA plays a key role in heat-induced dispersal of pneumococcal biofilms.
The serine protease HtrA plays a key role in heat-induced dispersal of pneumococcal biofilms.
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DOI：
10.1038/s41598-020-80233-0
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发表时间：
2020-12-31
影响因子：
4.6
通讯作者：
Hakansson AP
中科院分区：
文献类型：
--
作者：
Chao Y;Bergenfelz C;Sun R;Han X;Achour A;Hakansson AP
肺炎链球菌（肺炎球菌）通过形成多细胞生物膜而定殖于人鼻咽部。由于高水平的无症状携带，转变为感染，如中耳炎，肺炎，败血症和脑膜炎，经常发生，肺炎球菌仍然是全球疾病和死亡的主要原因。病毒感染和病毒诱导的反应，如温度升高（发烧），触发有毒细菌从定殖生物膜中释放。尽管我们假设包裹细菌的生物膜基质的破坏是必要的，但在生物膜扩散过程中涉及肺炎球菌外出的确切机制仍然未知。在这里，我们利用已建立的体外生物膜分散模型来研究蛋白酶参与细菌从肺炎球菌生物膜中排出。我们证明了蛋白酶活性的重要性，通过增加细菌释放后，加入蛋白酶和减少热诱导的生物膜分散在蛋白酶抑制剂的存在下。我们确定了一个关键的作用，表面暴露的丝氨酸蛋白酶HtrA，但不是PrtA，在热诱导的生物膜分散。与野生型等基因菌株相比，htrA阴性生物膜的细菌释放显着减少，但在添加重组HtrA后恢复并增加至野生型水平以上。了解细菌排出的具体机制可能为未来的策略提供新的靶点，这些策略旨在特异性干扰疾病进展而不干扰鼻咽生物膜定植。
Streptococcus pneumoniae (the pneumococcus) colonizes the human nasopharynx by forming multicellular biofilms. Due to the high level of asymptomatic carriage, transition to infections, such as otitis media, pneumonia, sepsis, and meningitis, occurs often enough that the pneumococcus remains a major cause of disease and death globally. Virus infection and virus-induced responses, such as increased temperature (fever), trigger release of virulent bacteria from colonizing biofilms. The exact mechanisms involved in pneumococcal egress during biofilm dispersal remain unknown, although we hypothesize that disruption of the biofilm matrix encasing the bacteria is necessary. Here, we utilized established in vitro biofilm dispersal models to investigate the involvement of proteases in bacterial egress from pneumococcal biofilms. We demonstrate the importance of protease activity, both through increased bacterial release following addition of proteases and reduced heat-induced biofilm dispersal in the presence of protease inhibitors. We identify a key role for the surface-exposed serine protease HtrA, but not PrtA, in heat-induced biofilm dispersal. Bacterial release from htrA-negative biofilms was significantly reduced compared to wild-type isogenic strains but was restored and increased above wild-type levels following addition of recombinant HtrA. Understanding the specific mechanisms involved in bacterial egress may provide novel targets for future strategies aimed to specifically interfere with disease progression without disturbing nasopharyngeal biofilm colonization.
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影响因子：
6.4
作者：
Blanchette-Cain K;Hinojosa CA;Akula Suresh Babu R;Lizcano A;Gonzalez-Juarbe N;Munoz-Almagro C;Sanchez CJ;Bergman MA;Orihuela CJ
通讯作者：
Orihuela CJ
影响因子：
4.2
作者：
Hussain, M;Melegaro, A;Miller, E
通讯作者：
Miller, E
DOI：
10.1007/978-1-4939-9199-0_13
发表时间：
2019-01-01
期刊：
STREPTOCOCCUS PNEUMONIAE
影响因子：
--
作者：
Chao, Yashuan;Bergenfelz, Caroline;Hakansson, Anders P.
通讯作者：
Hakansson, Anders P.
影响因子：
3.1
作者：
Cho, Christine;Chande, Aroon;Apicella, Michael A.
通讯作者：
Apicella, Michael A.
影响因子：
3.1
作者：
Elzer, PH;Phillips, RW;Roop, RM
通讯作者：
Roop, RM