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一种新型噬菌体,可通过与嵌合溶菌酶CHAPSH3b和万古霉素联合使用来去除生物膜。

A new bacteriophage infecting with potential for removing biofilms by combination with chimeric lysin CHAPSH3b and vancomycin.

作者信息

Duarte Ana Catarina, Fernández Lucía, Rodríguez Ana, García Pilar

机构信息

Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Oviedo, Asturias, Spain.

DairySafe Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.

出版信息

mSphere. 2025 Mar 25;10(3):e0101424. doi: 10.1128/msphere.01014-24. Epub 2025 Feb 21.

Abstract

is the cause of serious skin and prosthetic joint infections despite being a common inhabitant of human body surfaces. However, both the rise in antibiotic resistance in this species and its ability to form biofilms are increasingly limiting the available therapeutic options against these illnesses. In this landscape, phage therapy stands out as an interesting alternative to antibiotics. In the present study, we report the isolation and characterization of a novel virulent phage infecting ( phage IPLA-AICAT), which belongs to the family. The estimated genome size of this virus is 139,941 bp, and sequence analysis demonstrated the absence of antibiotic resistance genes and virulence factors. This phage infects a high proportion (79%) of clinically relevant strains and exhibits antibiofilm activity. Moreover, a combination of this phage with other antimicrobials, i.e., vancomycin and the lytic protein CHAPSH3b, further improved the reduction in surface-attached bacteria. Notably, the combination of phage IPLA-AICAT (10 PFU/mL) and CHAPSH3b (8 µM), originally designed to target , was able to reduce the number of viable cells by 3.06 log units in 5-h-old biofilms. In 24-h-old biofilms, the reduction was also significant after 6 h of treatment (2.06 log units) and 24 h of treatment (2.52 log units). These results confirm our previous data regarding the potential of phage-lysin mixtures against staphylococcal biofilms.IMPORTANCE is one of the main causes to device-associated infections mostly due to its ability to form stable biofilms attached to human tissues. Besides the inherent antimicrobial tolerance of biofilms, this microorganism is also increasingly becoming resistant to standard-of-care antibiotics. To fight against this problem, phage therapy is a viable option to complement the available antibiotics in the treatment of recalcitrant infections. This work describes a new phage infecting clinical strains that is a member of the family and the combination with other antimicrobials to further improve the reduction of biofilms. Together with the significant progress achieved in the development of diagnostic tools, phages and their derived proteins will bring us much closer to a therapeutic landscape in which we are not so heavily reliant on antibiotics to combat bacterial pathogens.

摘要

尽管是人体表面的常见寄居菌,但它却是严重皮肤和人工关节感染的病因。然而,该菌种抗生素耐药性的上升及其形成生物膜的能力,越来越限制了针对这些疾病的可用治疗选择。在这种情况下,噬菌体疗法作为抗生素的一种有趣替代方案脱颖而出。在本研究中,我们报告了一种新型烈性噬菌体(噬菌体IPLA - AICAT)的分离和特性,该噬菌体属于 科。这种病毒的估计基因组大小为139,941 bp,序列分析表明其不存在抗生素耐药基因和毒力因子。这种噬菌体可感染高比例(79%)的临床相关 菌株,并具有抗生物膜活性。此外,这种噬菌体与其他抗菌剂(即万古霉素和裂解蛋白CHAPSH3b)联合使用,进一步提高了对表面附着细菌的清除效果。值得注意的是,最初设计用于靶向 的噬菌体IPLA - AICAT(10 PFU/mL)和CHAPSH3b(8 µM)的组合,能够使5小时龄生物膜中的活细胞数量减少3.06个对数单位。在24小时龄生物膜中,治疗6小时(减少2.06个对数单位)和治疗24小时(减少2.52个对数单位)后,减少量也很显著。这些结果证实了我们之前关于噬菌体 - 溶菌酶混合物对抗葡萄球菌生物膜潜力的数据。重要性 是与装置相关感染的主要原因之一,主要是因为它能够形成附着在人体组织上的稳定生物膜。除了生物膜固有的抗菌耐受性外,这种微生物对标准护理抗生素的耐药性也日益增强。为了解决这个问题,噬菌体疗法是在治疗顽固性感染时补充现有抗生素的可行选择。这项工作描述了一种感染 临床菌株的新型噬菌体,它是 科的成员,以及与其他抗菌剂联合使用以进一步提高生物膜清除效果。随着诊断工具开发取得的重大进展,噬菌体及其衍生蛋白将使我们更接近一个不那么严重依赖抗生素来对抗细菌病原体的治疗前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d13/11934314/d5cc58df0406/msphere.01014-24.f001.jpg

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