Infectious disease is a therapeutic arena in which there is a constant need for new drugs to combat waves of resistant microorganisms (bacteria, fungi, parasites, viruses) that are selected for by widespread application of any microbial agents. For antibacterial agents the problem has been exacerbated over the past decade both by the spread of clinically significant multiply drug-resistant Gram-negative pathogens and Gram-positive pathogens and the exit of several major pharmaceutical companies from this therapeutic space¹.

Soil microbes represent an important source of biologically active compounds. These molecules present original and unexpected structure and are selective inhibitors of their molecular targets. Many of the products currently used for human or animal therapy, in animal husbandry and in agriculture are produced by microbial fermentation, or are derived from chemical modification of a microbial products. These products have been obtained after a few decades of intensive screening involving probably millions of microorganisms. Thus, new bioactive metabolites continue to be identified from microbial sources, thanks to the large variety of existing strains².

The purpose of this work was to search for novel antimicrobial agents, inhibitors of DD-peptidases (EC 3.4.16.4), microbial secondary metabolites from our collection of terrestrial streptomycetes strains. DD-carboxy­peptidases/trans­peptidases are the enzymes involved in peptide cross-linking during the last stage of bacterial cell wall peptidoglycan biosynthesis. We used DD-peptidase 64-575 II³. From the collection of streptomycetes 118 strains (110 of  Streptomyces, 8 of  Saccharopolyspora) of 56 species belonging to 45 clusters were tested for production of DD-peptidases inhibitors. 21 % of these strains  produced DD-peptidase 64-575 II inhibitors, 27 % of strains produced β-lactamases and 8 % of strains  represented both activities.

¹Walsh Ch.T., Wright G.D.: Antimicrobials, Current Op. Microbiol. 12, 473-475, 2009.

²Donadio S., Monciardini P., Alduina R., Mazza P., Chiocchini C., Cacaletti L., Sosio M., Puglia A.M.: Microbial technologies for the discovery of novel bioactive metabolites, J. Biotechnol. 99, 187-198, 2002.

³Solecka J., Kurzatkowski W.: Affinity of exocellular DD-carboxypeptidase/transpeptidase from Saccharopolyspora erythraea PZH 64-575 to beta-lactam compounds. Med. Dosw. Mikrobiol. 51, 151–165, 1999.

Acknowledgement: This work is co-financed from European Regional Development Fund within Operational Programme  „Innovative Economy”, the project number UDA-POIG.01.03.01-14-136/09-00

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