Pseudomonas aeruginosa biofilm dispersion by the mouse antimicrobial peptide CRAMP

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a known bacterium that produces biofilms and causes severe infection. Furthermore, P. aeruginosa biofilms are extremely difficult to eradicate, leading to the development of chronic and antibiotic-resistant infections. Our previous study showed that a cathelicidin-related antimicrobial peptide (CRAMP) inhibits the formation of P. aeruginosa biofilms and markedly reduces the biomass of preformed biofilms, while the mechanism of eradicating bacterial biofilms remains elusive. Therefore, in this study, the potential mechanism by which CRAMP eradicates P. aeruginosa biofilms was investigated through an integrative analysis of transcriptomic, proteomic, and metabolomic data. The omics data revealed CRAMP functioned against P. aeruginosa biofilms by different pathways, including the Pseudomonas quinolone signal (PQS) system, cyclic dimeric guanosine monophosphate (c-di-GMP) signalling pathway, and synthesis pathways of exopolysaccharides and rhamnolipid. Moreover, a total of 2914 differential transcripts, 785 differential proteins, and 280 differential metabolites were identified. A series of phenotypic validation tests demonstrated that CRAMP reduced the c-di-GMP level with a decrease in exopolysaccharides, especially alginate, in P. aeruginosa PAO1 biofilm cells, improved bacterial flagellar motility, and increased the rhamnolipid content, contributing to the dispersion of biofilms. Our study provides new insight into the development of CRAMP as a potentially effective antibiofilm dispersant.

The Impact of the Virulence of Pseudomonas aeruginosa Isolated from Dogs

“…The higher MICs for biofilm-embedded bacteria also suggest that treatment with neomycin, polymyxin B, gentamicin, or enrofloxacin may be less effective in treating chronic otitis caused by P. aeruginosa . Thereby, dogs can serve as a model for human infections; by studying P. aeruginosa biofilms in dogs, researchers can gain a better understanding of how these structures contribute to infection and develop more effective treatments [ 68 , 70 ].…”

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

“…Stably infected Caco-2 intestinal cells expressing HBD-2 and HBD-3 showed antibiofilm activity against P. aeruginosa, indicating that therapeutic strategies that enhance endogenous cellular AMP production might be successful as antibiofilm therapy [56]. The treatment of P. aeruginosa with CRAMP led to the dispersion of established biofilms by affecting exopolysaccharides, as well as promoting the flagellar motility of the bacteria inside the biofilm [57]. Yasir et al generated melimine, a chimeric AMP from melittin and protamine, which inhibited biofilm formation by >75% at one-fold MIC by depolarizing the cell membranes of biofilm cells.…”

Anti-biofilm activity of antimicrobial peptide CRAMP-34 by regulating 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (KduD) of Escherichia coli

“…Our previous studies have shown that the murine antimicrobial peptide (AMP) CRAMP-34 inhibits bio lm formation and eradicates the mature bio lms of the bio lm model strain Pseudomonas aeruginosa PAO1 [19,20]. However, whether CRAMP-34 has the same inhibitory effect on E. coli bio lms is yet to be clari ed.…”