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Synthetic polypeptide adjuvant-antibiotic combination eradicates polymicrobial assemblies, dormant bacteria and

Swagatam Barman1, Md Waliullah Hossain2, Aiswarya Chandrasseril Bansidhar2

  • 1Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States; Department of Environmental Health Sciences, University of South Carolina, Columbia, South Carolina, 29208, United States.

Biomaterials
|July 28, 2026
PubMed

Insights

Poly(D-peptide) (D-PP) adjuvants enhance antibiotic effectiveness against multidrug-resistant (MDR) Gram-negative bacteria. These combinations combat biofilms, dormant cells, and reduce resistance development, offering a new strategy for persistent infections.

Area of Science:

  • Microbiology
  • Drug Discovery
  • Biotechnology

Background:

  • Multidrug-resistant (MDR) Gram-negative bacteria pose a significant global health threat.
  • Treating complex infections involving biofilms, dormant cells, and polymicrobial communities remains challenging.
  • Novel strategies are needed to overcome existing antibiotic limitations.

Purpose of the Study:

  • To evaluate the efficacy of poly(D-peptide) (D-PP) as an adjuvant in combination with antibiotics against MDR Gram-negative bacteria.
  • To investigate the adjuvant's impact on bacterial biofilms, dormant subpopulations, and polymicrobial infections.
  • To elucidate the mechanisms underlying D-PP's synergistic effects and its role in preventing resistance.

Main Methods:

  • Combination therapy testing of D-PP with various antibiotic classes against planktonic and sessile bacteria.
  • Assessment of D-PP combinations against dormant bacterial subpopulations and polymicrobial cultures.
  • Biofilm eradication assays and transcriptomic analysis to identify differentially expressed genes (DEGs).

Main Results:

  • D-PP significantly potentiated antibiotic activity, leading to rapid bactericidal effects against planktonic Gram-negative pathogens.
  • Combinations restored antibiotic susceptibility in dormant bacterial subpopulations and reduced both Gram-negative and Gram-positive species in polymicrobial settings.
  • D-PP-rifampicin demonstrated moderate biofilm eradication of P. aeruginosa, and transcriptomic data indicated membrane perturbation as a key mechanism.

Conclusions:

  • Membrane-active polypeptide adjuvants like D-PP can enhance antibiotic efficacy against diverse bacterial states and environments.
  • These combinations offer a promising strategy to combat persistent and multidrug-resistant infections.
  • D-PP reduces bacterial resistance development to certain antibiotics, unlike polymyxin B.

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