1. Novel synthetic polymyxins kill Gram-positive bacteria
- Author
-
Miguel Viñas, Josep M. Sierra, Isabel Pérez-Guillén, Teresa Vinuesa, Francesc Rabanal, and Héctor Rudilla
- Subjects
Models, Molecular ,0301 basic medicine ,Microbiology (medical) ,Staphylococcus aureus ,Agents antiinfecciosos ,Vancomycin-resistant Staphylococcus aureus ,Cell Survival ,medicine.drug_class ,Polymyxin ,030106 microbiology ,Molecular Conformation ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Nosocomial infections ,medicine ,Humans ,media_common.cataloged_instance ,Pharmacology (medical) ,Polymyxins ,European union ,media_common ,Pharmacology ,Microbial Viability ,business.industry ,biochemical phenomena, metabolism, and nutrition ,Antimicrobial ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,Infeccions nosocomials ,Anti-Bacterial Agents ,030104 developmental biology ,Infectious Diseases ,Biofilms ,Hepatocytes ,Colistin ,Vancomycin ,Anti-infective agents ,business ,medicine.drug - Abstract
Background Staphylococcus aureus, including 'superbug' MRSA, is a major cause of nosocomial infections. In the European Union, up to 171 200 new nosocomial MRSA infections are acquired annually, and in the USA S. aureus causes more deaths than HIV/AIDS and tuberculosis combined. MRSA is also the first group of pathogens that infect the pulmonary tract in young patients with cystic fibrosis. Objectives We describe two newly developed and synthesized colistin (polymyxin E)-inspired molecules. Methods A collection of several isolates of S. aureus [including MRSA and vancomycin-resistant S. aureus (VRSA)] was tested. To check the antimicrobial activity, we performed time-kill curves, growth curves, biofilm eradication, toxicity and isothermal titration calorimetry. Results Both peptides showed high antimicrobial activities (MIC 4 mg/L) and low relative toxicities (selectivity index close to 23). Conclusions Successful production of polymyxin-scaffold molecules active against S. aureus, both MRSA and VRSA, opens up new approaches to the treatment of these complicated infections.
- Published
- 2018