Novel vancomycin–peptide conjugate as potent antibacterial agent against vancomycin-resistant Staphylococcus aureus

Pavlina Jelinkova,1 Zbynek Splichal,1,2 Ana Maria Jimenez Jimenez,1,2 Yazan Haddad,1,2 Aninda Mazumdar,1,2 Vishma Pratap Sur,1,2 Vedran Milosavljevic,1,2 Pavel Kopel,1,2 Hana Buchtelova,1 Roman Guran,1,2 Ondrej Zitka,1,2 Lukas Richtera,1,2 Dagmar Hegerova,1,2 Zbynek Heger,1,2 Amitava Moulick,1,2 Vojtech Adam1,2 1Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska, Brno, Czech Republic; 2Central European Institute of Technology, Brno University of Technology, Purkynova, Brno, Czech Republic Background: Increase in vancomycin (Van)-resistant bacterial strains including vancomycin-resistant Staphylococcus aureus (VRSA) and lack of new effective antibiotics have become a formidable health problem. Materials and methods: We designed a new conjugate composed of Van and a peptide Hecate (Hec; Van/Hec), and its potential antimicrobial activity was evaluated. Results: Results from disk diffusion test, time-kill assay, determination of minimum inhibitory concentration (MIC), microscopy, and comet assay showed strong antimicrobial effects of Van/Hec against wild-type, methicillin-resistant Staphylococcus aureus (MRSA) and VRSA. Microscopy revealed that the exposure to Van/Hec results in disruption of bacterial cell integrity in all tested strains, which was not observed in case of Van or Hec alone. Conclusion: Overall, we showed that the preparation of conjugates from antibiotics and biologically active peptides could help us to overcome the limitation of the use of antibiotic in the treatment of infections caused by multidrug-resistant bacteria. Keywords: vancomycin, antibacterial, Staphylococcus aureus, antibiotic resistance, peptide