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Nucleases of bacterial pathogens as virulence factors, therapeutic targets and diagnostic markers.
International Journal of Medical Microbiology ( IF 4.5 ) Pub Date : 2019-08-30 , DOI: 10.1016/j.ijmm.2019.151354
Prince Sharma 1 , Nisha Garg 1 , Anshul Sharma 1 , Neena Capalash 2 , Ravinder Singh 1
Affiliation  

New frontiers of therapy are being explored against the upcoming bacterial diseases rendered untreatable due to multiple, extreme and pan- antibiotic resistance. Nucleases are ubiquitous in bacterial pathogens performing various functions like acquiring nucleotide nutrients, allowing or preventing uptake of foreign DNA, controlling biofilm formation/dispersal/architecture, invading host by tissue damage, evading immune defence by degrading DNA matrix of neutrophil extracellular traps (NETs) and immunomodulating the host immune response. Secretory nucleases also provide means of survival to other bacteria like iron-reducing Shewanella and such functions help them adapt and survive proficiently. Other than their pro-pathogen roles in survival, nucleases can be used directly as therapeutics. One of the powerful armours of pathogens is the formation of biofilms, thus helping them resist and persist in the harshest of environments. As eDNA forms the structural and binding component of biofilm, nucleases can be used against the adhering component, thus increasing the permeability of antimicrobial agents. Nucleases have recently become a model system of intense study for their biological functions and medical applications in diagnosis, immunoprophylaxis and therapy. Rational implications of these enzymes can impact human medicine positively in future by opening new ways for therapeutics which have otherwise reached saturation due to multi drug resistance.



中文翻译:

细菌病原体的核酸酶作为毒力因子,治疗靶标和诊断标志物。

正在探索治疗的新领域,以应对由于多重,极端和泛抗生素耐药性而变得无法治愈的细菌疾病。核酸酶在细菌病原体中无处不在,具有各种功能,例如获取核苷酸营养,允许或阻止外来DNA的摄取,控制生物膜的形成/分散/结构,因组织损伤而侵入宿主,通过降解嗜中性白细胞胞外陷阱(NETs)的DNA基质来逃避免疫防御。并免疫调节宿主的免疫反应。分泌型核酸酶还为其他细菌(如还原铁的希瓦氏菌)提供了生存手段这些功能有助于他们适应并有效生存。除了其在病原体中的生存作用外,核酸酶还可以直接用作治疗剂。病原体的强大防护之一是生物膜的形成,从而帮助它们抵抗并在最恶劣的环境中持久存在。由于eDNA形成生物膜的结构和结合成分,因此可以使用核酸酶对抗粘附成分,从而提高抗微生物剂的渗透性。核酸酶由于其生物学功能和在诊断,免疫预防和治疗中的医学应用,最近已成为一个广泛研究的模型系统。这些酶的合理含义可以通过开辟新的治疗方法来对人类医学产生积极的影响,而新方法由于多种耐药性而已达到饱和。

更新日期:2019-08-30
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