DJK-5, an anti-biofilm peptide, increases Staphylococcus aureus sensitivity to colistin killing in co-biofilms with Pseudomonas aeruginosa.

IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Samuel J T Wardell, Deborah B Y Yung, Anupriya Gupta, Mihnea Bostina, Joerg Overhage, Robert E W Hancock, Daniel Pletzer
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Abstract

Chronic infections represent a significant global health and economic challenge. Biofilms, which are bacterial communities encased in an extracellular polysaccharide matrix, contribute to approximately 80% of these infections. In particular, pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus are frequently co-isolated from the sputum of patients with cystic fibrosis and are commonly found in chronic wound infections. Within biofilms, bacteria demonstrate a remarkable increase in resistance and tolerance to antimicrobial treatment. We investigated the efficacy of combining the last-line antibiotic colistin with a membrane- and stringent stress response-targeting anti-biofilm peptide DJK-5 against co-biofilms comprised of multidrug-resistant P. aeruginosa and methicillin-resistant S. aureus (MRSA). Colistin lacks canonical activity against S. aureus. However, our study revealed that under co-biofilm conditions, the antibiofilm peptide DJK-5 synergized with colistin against S. aureus. Similar enhancement was observed when daptomycin, a cyclic lipopeptide against Gram-positive bacteria, was combined with DJK-5, resulting in increased activity against P. aeruginosa. The combinatorial treatment induced morphological changes in both P. aeruginosa and S. aureus cell shape and size within co-biofilms. Importantly, our findings also demonstrate synergistic activity against both P. aeruginosa and S. aureus in a murine subcutaneous biofilm-like abscess model. In conclusion, combinatorial treatments with colistin or daptomycin and the anti-biofilm peptide DJK-5 show significant potential for targeting co-biofilm infections. These findings offer promising avenues for developing new therapeutic approaches to combat complex chronic infections.

慢性感染是一项重大的全球卫生和经济挑战。生物膜是包裹在细胞外多糖基质中的细菌群落,约占这些感染的80%。特别是,铜绿假单胞菌和金黄色葡萄球菌等病原体经常从囊性纤维化患者的痰中分离出来,并且常见于慢性伤口感染。在生物膜内,细菌对抗菌素治疗的耐药性和耐受性显著增加。我们研究了最后一线抗生素粘菌素与膜和严格应激反应靶向抗生物膜肽DJK-5联合治疗由多重耐药铜绿假单胞菌和耐甲氧西林金黄色葡萄球菌(MRSA)组成的共生物膜的疗效。粘菌素缺乏抗金黄色葡萄球菌的典型活性。然而,我们的研究发现,在共生物膜条件下,抗生物膜肽DJK-5与粘菌素协同作用,对抗金黄色葡萄球菌。当达托霉素(一种抗革兰氏阳性菌的环脂肽)与DJK-5联合使用时,也观察到类似的增强作用,从而增加了抗铜绿假单胞菌的活性。联合处理诱导铜绿假单胞菌和金黄色葡萄球菌在共生物膜内的细胞形状和大小发生形态学变化。重要的是,我们的研究结果也证明了在小鼠皮下生物膜样脓肿模型中对铜绿假单胞菌和金黄色葡萄球菌的协同作用。综上所述,粘菌素或达托霉素与抗生物膜肽DJK-5联合治疗具有显著的靶向共生物膜感染的潜力。这些发现为开发对抗复杂慢性感染的新治疗方法提供了有希望的途径。
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来源期刊
npj Biofilms and Microbiomes
npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology
CiteScore
12.10
自引率
3.30%
发文量
91
审稿时长
9 weeks
期刊介绍: npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.
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