RESUMO
Many pathogenic bacteria and microscopic fungi form rigid polymicrobial biofilms this way enhancing their resistant to treatment. A series of novel pyridoxine-based quaternary ammonium derivatives of terbinafine characterized by both antifungal and antibacterial activities was designed. The leading compound named KFU-127 exhibits promising antifungal and antibacterial activities against various bacteria and micromycetes in both planktonic and biofilm-embedded forms demonstrating MIC values comparable with those of conventional antifungals and antimicrobials. Similar to other antiseptics like benzalkonium chloride and miramistin, KFU-127 is considerably toxic for eukaryotic cells that limits is application to topical treatment options. On the other hand, KFU-127 reduces the number of viable biofilm-embedded bacteria and C. albicans by 3 orders of magnitude at concentrations 2-4 times lower than those of reference drugs and successfully eradicates S. aureus-C. albicans mixed biofilms. The mechanism of antimicrobial action of KFU-127 is bimodal including both membrane integrity damage and pyridoxal-dependent enzymes targeting. We expect that this bilateral mechanism would result in lower rates of resistance development in both fungal and bacterial pathogens. Taken together, our data suggest KFU-127 as a new promising broad spectrum topical antimicrobial capable of one-shot targeting of bacterial and fungal-bacterial biofilms.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Piridoxina/farmacologia , Compostos de Amônio Quaternário/farmacologia , Terbinafina/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fungos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piridoxina/síntese química , Piridoxina/química , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade , Terbinafina/síntese química , Terbinafina/químicaRESUMO
Here we present a draft genome of Pseudomonas stutzeri strain KOS6. This strain was isolated from industrial hydrocarbon sludge as a diazotrophic microorganism. It represents one of the major parts of the culturable community of the waste and has potential importance for phytoremediation technology.