Unnatural Amino‐Acid‐Based Star‐Shaped Poly(<scp>l</scp>‐Ornithine)s as Emerging Long‐Term and Biofilm‐Disrupting Antimicrobial Peptides to Treat <i>Pseudomonas aeruginosa</i>‐Infected Burn Wounds

Pan, Miao; Chen, Lu; Zheng, Maochao; Zhou, Wen; Song, Fuling; Chen, Weidong; Yao, Fen; Liu, Daojun; Cai, Jianfeng

doi:10.1002/adhm.202200944

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, it would be interesting to investigate the length of δ-poly-L-ornithine produced by A. baumannii , since longer chain may have a higher anti-fungal activity or maybe a different role altogether. Synthetic poly(L-ornithine) was also found to have biofilm-disrupting capacity 41 . Similarly, our results showed that an A. baumannii 307 knockout strain of posA gene had a modest increase in biofilm formation compared to the wild type indicating δ-poly-L-ornithine may have a role in the detachment of cells from biofilm.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structural and functional insights into δ-poly-L-ornithine polymer biosynthesis from Acinetobacter baumannii

Patel,

Gulick

2023

Commun Biol

View full text Add to dashboard Cite

Cationic homo-polyamino acid (CHPA) peptides containing isopeptide bonds of diamino acids have been identified from Actinomycetes strains. However, none has been reported from other bacteria. Here, we report a δ-poly-L-ornithine synthetase from Acinetobacter baumannii, which we name PosA. Surprisingly, structural analysis of the adenylation domain and biochemical assay shows L-ornithine as the substrate for PosA. The product from the enzymatic reaction was purified and identified as poly-L-ornithine composed of 7-12 amino acid units. Chemical labeling of the polymer confirmed the isopeptide linkage of δ-poly-L-ornithine. We examine the biological activity of chemically synthesized 12-mer δ-poly-L-ornithine, illustrating that the polymer may act as an anti-fungal agent. Structures of the isolated adenylation domain from PosA are presented with several diamino acids and biochemical assays identify important substrate binding residues. Structurally-guided genome-mining led to the identification of homologs with different substrate binding residues that could activate additional substrates. A homolog from Bdellovibrionales sp. shows modest activity with L-arginine but not with any diamino acids observed to be substrates for previously examined CHPA synthetases. Our study indicates the possibility that additional CHPAs may be produced by various microbes, supporting the further exploration of uncharacterized natural products.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The search for anti-microbial peptides may aid the discovery of new therapeutics. Identifying natural product analogs has been found to be a successful strategy for discovering effective antimicrobials 41 . With the advent of genomic data, many homologous sequences of εPL synthetase could be found.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional insights into δ-poly-L-ornithine polymer biosynthesis from Acinetobacter baumannii

Patel,

Gulick

2023

Commun Biol

View full text Add to dashboard Cite

show abstract

“…Pseudomonas aeruginosa is a prevalent human opportunistic pathogen that often induces chronic infections, ultimately leading to clinical treatment failure. P. aeruginosa is characterized by the ability to easily develop drug resistance, accompanied by a rapid variation in its resistance profile (Pan et al 2022 ). Biofilm formation represents a critical mechanism underlying antibiotic resistance in P. aeruginosa infections (Ciofu et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro

Zhang,

Mi,

Wang

et al. 2024

Arch Microbiol

View full text Add to dashboard Cite

Pseudomonas aeruginosa is an opportunistic gram-negative pathogenic microorganism that poses a significant challenge in clinical treatment. Antibiotics exhibit limited efficacy against mature biofilm, culminating in an increase in the number of antibiotic-resistant strains. Therefore, novel strategies are essential to enhance the effectiveness of antibiotics against Pseudomonas aeruginosa biofilms. D-histidine has been previously identified as a prospective anti-biofilm agent. However, limited attention has been directed towards its impact on Pseudomonas aeruginosa. Therefore, this study was undertaken to explore the effect of D-histidine on Pseudomonas aeruginosa in vitro. Our results demonstrated that D-histidine downregulated the mRNA expression of virulence and quorum sensing (QS)-associated genes in Pseudomonas aeruginosa PAO1 without affecting bacterial growth. Swarming and swimming motility tests revealed that D-histidine significantly reduced the motility and pathogenicity of PAO1. Moreover, crystal violet staining and confocal laser scanning microscopy demonstrated that D-histidine inhibited biofilm formation and triggered the disassembly of mature biofilms. Notably, D-histidine increased the susceptibility of PAO1 to amikacin compared to that in the amikacin-alone group. These findings underscore the efficacy of D-histidine in combating Pseudomonas aeruginosa by reducing biofilm formation and increasing biofilm disassembly. Moreover, the combination of amikacin and D-histidine induced a synergistic effect against Pseudomonas aeruginosa biofilms, suggesting the potential utility of D-histidine as a preventive strategy against biofilm-associated infections caused by Pseudomonas aeruginosa.

show abstract

Design and optimization of ε-poly-l-lysine with specific functions for diverse applications

Wang,

et al. 2024

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

Unnatural Amino‐Acid‐Based Star‐Shaped Poly(l‐Ornithine)s as Emerging Long‐Term and Biofilm‐Disrupting Antimicrobial Peptides to Treat Pseudomonas aeruginosa‐Infected Burn Wounds

Cited by 3 publications

References 0 publications

Structural and functional insights into δ-poly-L-ornithine polymer biosynthesis from Acinetobacter baumannii

Structural and functional insights into δ-poly-L-ornithine polymer biosynthesis from Acinetobacter baumannii

D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro

Design and optimization of ε-poly-l-lysine with specific functions for diverse applications

Contact Info

Product

Resources

About