A chionodracine-derived peptide, KHS-Cnd, as an anti-virulence agent against multidrug-resistant clinical strains.

Marco Artini, Irene Paris, Esther Imperlini, Francesco Buonocore, Gianluca Vrenna, Rosanna Papa, Laura Selan
Author Information
  1. Marco Artini: Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
  2. Irene Paris: Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
  3. Esther Imperlini: Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy.
  4. Francesco Buonocore: Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy.
  5. Gianluca Vrenna: Research Unit of Diagnostical and Management Innovations, Children's Hospital and Institute Research Bambino Ges��, Rome, Italy.
  6. Rosanna Papa: Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
  7. Laura Selan: Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.

Abstract

About 71% of healthcare-associated infections are due to antibiotic-resistant bacteria, such as carbapenem-resistant , classified by World Health Organization into a critical priority group of pathogens. The antimicrobial resistance profile of relies on its ability to produce several virulence factors, including biofilm formation. Its ability to adhere and persist on surfaces as biofilm has contributed to its pathogenicity and drug resistance. In this study, the ability of an antimicrobial peptide (a chionodracine-derived peptide named KHS-Cnd) to inhibit or reduce biofilm formation was investigated as an example of a potential strategy to counteract infections caused by biofilm-forming pathogens. To this aim, the antimicrobial profiles were first analyzed in selected strains, two reference and six clinical strains, all biofilm-forming with different capability, regardless of whether they are drug resistant or sensitive. Successively, we investigated the bactericidal activity of the peptide that showed MIC values ranging from 5 to 10 ��M and a significative antibiofilm activity on all tested strains at sub-inhibitory concentrations. In fact, KHS-Cnd can hinder biofilm strains formation with an inhibition percentage ranging between 65% and 10%. Also a statistically significant reduction of mature biofilm ranging from 20% to 50% was observed in four out of eight tested strains. KHS-Cnd impacts various stages of biofilm formation, including the inhibition of surface-associated and twitching motilities depending on the different strain. In particular, our results showed that only two strains possessed surface-associated motility that was strongly impaired by KHS-Cnd treatment; three clinical strains, instead, showed twitching motility, whose inhibition for two of them was evident after 24 h of incubation with peptide. Moreover, the invasion of pulmonary cells by was significantly impaired with a reduction of about 32% after treatment with 1.25 ��M KHS-Cnd. Finally, when the peptide was used together with ceftazidime/avibactam against resistant strains, it was able to reduce the minimal inhibitory concentration of antibiotics needed to inhibit the microorganism growth.

Keywords

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MeSH Term

Acinetobacter baumannii
Biofilms
Microbial Sensitivity Tests
Drug Resistance, Multiple, Bacterial
Anti-Bacterial Agents
Humans
Acinetobacter Infections
Antimicrobial Peptides
Virulence
Virulence Factors

Chemicals

Anti-Bacterial Agents
Antimicrobial Peptides
Virulence Factors

Word Cloud

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