Progress towards the clinical use of antimicrobial peptides: challenges and opportunities.

INTRODUCTION: To overcome the challenge of multidrug resistance, natural and synthetic peptides are candidates to become the basis of innovative therapeutics, featuring diverse mechanisms of action. Traditionally, the time elapsed from medical discoveries to their application is long. The urgency derived from the emergence of antibiotic resistance recommends an acceleration of research to put the new weapons in the hands of clinicians. AREAS COVERED: This narrative review introduces ideas and suggestions of new strategies that may be used as a basis upon which to recommend reduced development times and to facilitate the arrival of new molecules in the fight against microbes. EXPERT OPINION: Although studies on new innovative antimicrobial treatments are being conducted, sooner rather than later, more clinical trials, preclinical and translational research are needed to promote the development of innovative antimicrobial treatments for multidrug resistant infections. The situation is worrying, no less than that generated by pandemics such as the ones we have just experienced and conflicts such as world wars. Although from the point of view of human perception, resistance to antibiotics may not seem as serious as these other situations, it is possibly the hidden pandemic that most jeopardizes the future of medicine.

Efficient AntiMycolata Agents by Increasing the Lipophilicity of Known Antibiotics through Multicomponent Reactions.

New antibiotic agents were prepared using Povarov and Ugi multicomponent reactions upon the known drugs sulfadoxine and dapsone. The prepared derivatives, with increased lipophilicity, showed improved efficiency against Mycolata bacteria. Microbiological guidance for medicinal chemistry is a powerful tool to design new and effective antimicrobials. In this case, the readily synthesized compounds open new possibilities in the search for antimicrobials active on mycolic acid-containing bacteria.

Identification and characterization of a cell wall porin from Gordonia jacobaea.

Gordonia jacobaea is a bacterium belonging to the mycolata group characterized by its ability to produce carotenoids. Mycolic acids in the cell wall contribute to reducing the permeability of their envelopes requiring the presence of channel-forming proteins to allow the exchange of hydrophilic molecules with the surrounding medium. Identification and purification of the channel-forming proteins was accomplished by SDS-PAGE, Mass spectrometry and Mass peptide fingerprinting and the channel-forming activity was studied by reconstitution in lipid bilayers. Here, we describe for the first time the presence of a cell-wall protein from G. jacobaea with channel-forming activity. Our results suggest that this protein bears a low similarity to other hypothetical proteins from the genus Gordonia of uncharacterized functions. The channel has an average single-channel conductance of 800 pS in 1 M KCl, is moderately anion-selective, and does not show any voltage dependence for voltages between +100 and -100 mV. The channel characteristics suggest that this protein could be of relevance in the import and export of negatively charged molecules across the cell wall. This could contribute to design treatments for mycobacterial infections, as well as being of interest in biotechnology applications.

Draft Genome Sequence of Dietzia maris DSM 43672, a Gram-Positive Bacterium of the Mycolata Group.

Here, we report the draft genome sequence of Dietzia maris, known previously as Rhodococcus maris It is 3,505,372 bp in size with a G+C content of 73%. The draft genome sequence will improve our understanding of Dietzia maris related to other mycolata species and constitutes a basic tool for exploring the cell wall proteins.