Impact of CRAMP-34 on Pseudomonas aeruginosa biofilms and extracellular metabolites

被引:1
|
作者
Wang, Shiyuan [1 ,2 ,3 ]
Ma, Chengjun [1 ,2 ,4 ]
Long, Jinying [1 ,2 ,4 ]
Cheng, Peng [1 ,2 ]
Zhang, Yang [2 ,5 ]
Peng, Lianci [1 ,2 ,4 ]
Fu, Lizhi [2 ,5 ]
Yu, Yuandi [2 ,5 ]
Xu, Dengfeng [2 ,5 ]
Zhang, Suhui [2 ,5 ]
Qiu, Jinjie [2 ,5 ]
He, Yuzhang [1 ,2 ,4 ]
Yang, Hongzao [1 ,2 ,4 ]
Chen, Hongwei [1 ,2 ,4 ]
机构
[1] Southwest Univ, Coll Vet Med, Chongqing, Peoples R China
[2] Collaborat Innovat Inst Natl Ctr Technol Innovat P, Chongqing, Peoples R China
[3] Nanjing Agr Univ, Coll Vet Med, Nanjing, Peoples R China
[4] Southwest Univ, Med Res Inst, Immunol Res Ctr, Chongqing, Peoples R China
[5] Inst Vet Med Acad Anim Sci, Inst Vet Sci & Med, Chongqing, Peoples R China
来源
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY | 2023年 / 13卷
关键词
Pseudomonas aeruginosa; CRAMP-34; anti-biofilm peptides; extracellular metabolites; synergistic effect; NUTRIENT-INDUCED DISPERSION; ANTIMICROBIAL PEPTIDE;
D O I
10.3389/fcimb.2023.1295311
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Biofilm is a structured community of bacteria encased within a self-produced extracellular matrix. When bacteria form biofilms, they undergo a phenotypic shift that enhances their resistance to antimicrobial agents. Consequently, inducing the transition of biofilm bacteria to the planktonic state may offer a viable approach for addressing infections associated with biofilms. Our previous study has shown that the mouse antimicrobial peptide CRAMP-34 can disperse Pseudomonas aeruginosa (P. aeruginosa) biofilm, and the potential mechanism of CRAMP-34 eradicate P. aeruginosa biofilms was also investigated by combined omics. However, changes in bacterial extracellular metabolism have not been identified. To further explore the mechanism by which CRAMP-34 disperses biofilm, this study analyzed its effects on the extracellular metabolites of biofilm cells via metabolomics. The results demonstrated that a total of 258 significantly different metabolites were detected in the untargeted metabolomics, of which 73 were downregulated and 185 were upregulated. Pathway enrichment analysis of differential metabolites revealed that metabolic pathways are mainly related to the biosynthesis and metabolism of amino acids, and it also suggested that CRAMP-34 may alter the sensitivity of biofilm bacteria to antibiotics. Subsequently, it was confirmed that the combination of CRAMP-34 with vancomycin and colistin had a synergistic effect on dispersed cells. These results, along with our previous findings, suggest that CRAMP-34 may promote the transition of PAO1 bacteria from the biofilm state to the planktonic state by upregulating the extracellular glutamate and succinate metabolism and eventually leading to the dispersal of biofilm. In addition, increased extracellular metabolites of myoinositol, palmitic acid and oleic acid may enhance the susceptibility of the dispersed bacteria to the antibiotics colistin and vancomycin. CRAMP-34 also delayed the development of bacterial resistance to colistin and ciprofloxacin. These results suggest the promising development of CRAMP-34 in combination with antibiotics as a potential candidate to provide a novel therapeutic approach for the prevention and treatment of biofilm-associated infections.
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页数:12
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