Novel synthetic polymyxins kill Gram-positive bacteria.

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.

New and old tools to evaluate new antimicrobial peptides.

The emergence of antimicrobial resistance due to the overuse of antimicrobials together with the existence of naturally untreatable infections well demonstrates the need for new instruments to fight microbes. Antimicrobial peptides (AMPs) are a promising family of molecules in this regard, because they abundantly occur in nature and the results of preliminary studies of their clinical potential have been encouraging. However, further progress will benefit from the standardization of research methods to assess the antimicrobial properties of AMPs. Here we review the diverse methods used to study the antimicrobial power of AMPs and recommend a pathway to explore new molecules. The use of new methodologies to quantitatively evaluate the physical effect on bacterial biofilms such as force spectroscopy and surface cell damage evaluation, constitute novel approaches to study new AMPs.

Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems.

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 µg/mL, whereas the MBEC of each antimicrobial separately was 500 µg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem.