Evaluating the antimicrobial and anti-biofilm activity of three synthetic antimicrobial Citropin analogs and their ability to fight against Staphylococcus aureus and Staphylococcus pseudintermedius

Author:

Salvado Matheus Gomes12,André Lialyz Soares Pereira34,Pereira Renata Freire Alves35,Pinheiro Felipe Ramos34,Barbosa Beatriz das Chagas3,Scaffo Julia Chaves3,Pereira Aramis José6,Arakaki Daniela Granja7,Xing Huihua6,de Oliveira Kelly Mari Pires8,de Andrade dos Santos João Víctor8,Sachs Daniela9,Aguiar-Alves Fabio10,Conda-Sheridan Martin6,Penna Bruno125ORCID

Affiliation:

1. Graduate Program in Veterinary Medicine, Fluminense Federal University , Niteroi, 24230-321 , Brazil

2. Gram Positive Cocci Laboratory, Fluminense Federal University , Niteroi, 24020-141 , Brazil

3. Molecular Epidemiology and Biotechnology Laboratory/Rodolpho Albino University Laboratory - Fluminense Federal University , Niteroi, 24241-000 , Brazil

4. Graduate Program in Pathology, Fluminense Federal University , Niteroi 24020-141 , Brazil

5. Graduate Program in Microbiology and Parasitology - Fluminense Federal University , Niteroi, 24020-141 , Brazil

6. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center , Omaha, NE 68198 , United States

7. Group of Spectroscopy and Bioinformatics Applied Biodiversity and Health, Mato Grosso do Sul Federal University , Pioneiros, 79070-900 , Brazil

8. Microbiological assays laboratory, Great Dourados Federal University , Dourados, 79.804-970 , Brazil

9. Microbiological Testing Laboratory Associated with Materials and Drugs of the Center for Studies, Research, and Innovation in Biofunctional Materials and Biotechnology, Federal University of Itajubá , Itajuba, 37500-903 , Brazil

10. Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University , West Palm Beach, FL 33403 , USA

Abstract

Abstract Aims We developed three new analogs of the antimicrobial peptide (AMP) Citropin 1.1: DAN-1–13, AJP-1–1, and HHX-2–28, and tested their potential antimicrobial and antibiofilm activities against Staphylococcus aureus and S. pseudintermedius. Potential cytotoxic or hemolytic effects were determined using cultured human keratinocytes and erythrocytes to determine their safety. Methods and results To assess the antimicrobial activity of each compound, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined against methicillin-resistant and methicillin-susceptible strains of S. aureus and S. pseudintermedius. Activity against newly formed and mature biofilms was determined in two clinical isolates using spectrophotometry and scanning electron microscopy (SEM). All three compounds exhibited antimicrobial and bactericidal activity against all studied S. aureus and S. pseudintermedius strains, with MICs ranging from 4–32 μg ml−1 and MBCs ranging from 8–128 μg ml−1. Subinhibitory concentrations of all compounds also showed ant-biofilm activity in the two tested isolates. All compounds exhibited limited cytotoxic and hemolytic activity. Conclusions Novel analogs of Citropin 1.1 exhibit antimicrobial and bactericidal activities against S. aureus and S. pseudintermedius isolates and inhibit the biofilm formation of these bacteria.

Funder

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Oxford University Press (OUP)

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