富含脯氨酸的抗菌肽 Api137 对猪血液中感染的猪或人肺炎克雷伯菌具有杀菌作用。

Proline-rich antimicrobial peptide Api137 is bactericidal in porcine blood infected ex vivo with a porcine or human Klebsiella pneumoniae strain.

机构信息

Institute of Bacteriology and Mycology, Faculty of Veterinary Medicine, University Leipzig, 04103 Leipzig, Germany.

Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy and Centre for Biotechnology and Biomedicine, Both University Leipzig, 04103 Leipzig, Germany.

出版信息

J Glob Antimicrob Resist. 2021 Mar;24:127-135. doi: 10.1016/j.jgar.2020.12.012. Epub 2020 Dec 26.

DOI:10.1016/j.jgar.2020.12.012

PMID:33373733

Abstract

OBJECTIVES

Klebsiella pneumoniae is an emerging invasive pathogen in humans and pigs. Resistance against multiple antibiotics in this species is a major health concern and the development of new antibiotics is urgently needed. The objective of this study was to investigate the effects of proline-rich antimicrobial peptides (PrAMPs) on the survival of K. pneumoniae strains in porcine blood.

METHODS

We established a bactericidal assay with K. pneumoniae in fresh blood drawn from 4-week-old piglets. PrAMPs, namely the apidaecins Api137 and Api802 as well as the oncocin Onc112, were added to ex vivo-infected whole blood samples in order to study their bactericidal effects and, in the case of Api137, also immune responses.

RESULTS

A porcine invasive and a human iucA+rmpA+ K. pneumoniae strain showed prominent proliferation in porcine blood. Application of Api137 resulted in a dose-dependent prominent bactericidal effect killing the invasive porcine K. pneumoniae strain. Addition of 8 μg/mL Api137 also resulted in complete killing of the human iucA+rmpA+ strain. Cytotoxicity, haemolysis and induction of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFα) in K. pneumoniae-infected porcine blood treated with Api137 was comparable with values obtained after application of 10 μg/mL cefquinome.

CONCLUSION

We describe a new non-rodent model for invasive K. pneumoniae bacteraemia and present promising data for the PrAMP Api137 for the control of infection with hypervirulent K. pneumoniae strains.

摘要

目的

肺炎克雷伯菌是一种新兴的人类和猪的侵袭性病原体。该物种对抗多种抗生素的耐药性是一个主要的健康问题，迫切需要开发新的抗生素。本研究的目的是研究富含脯氨酸的抗菌肽（PrAMPs）对猪血液中肺炎克雷伯菌菌株存活的影响。

方法

我们建立了一种用 4 周龄仔猪新鲜血液中的肺炎克雷伯菌进行杀菌测定的方法。添加富含脯氨酸的抗菌肽，即 apidaecins Api137 和 Api802 以及 oncocin Onc112，以研究它们对体外感染全血样本的杀菌作用，并且在 Api137 的情况下，还研究了它们对免疫反应的影响。

结果

一株猪侵袭性和一株人 iucA+rmpA+ 肺炎克雷伯菌在猪血液中表现出明显的增殖。应用 Api137 导致剂量依赖性的明显杀菌作用，可杀死侵袭性猪肺炎克雷伯菌。添加 8 μg/mL 的 Api137 也可完全杀死人 iucA+rmpA+ 株。用 Api137 处理感染肺炎克雷伯菌的猪血液中的细胞毒性、溶血和促炎细胞因子肿瘤坏死因子-α（TNFα）的诱导与应用 10 μg/mL 头孢喹肟获得的值相当。