Novel chemical countermeasures against staphylococcal biofilms

Abstract

Some natural and synthetic related pyrrolomycins, a family of halogenated pyrrole antibiotics, showed anti-biofilm properties in vitro at low concentration (0.045μg/mL) against preformed staphylococcal biofilms. Moreover, considering the human cell toxicity, the selectivity indexes (ratio of cytotoxicity to antibiofilm activity) of some of them were very interesting. The present study aims to investigate if the pyrrolomycins could also prevent staphylococcal biofilm formation. The evaluation of S.aureus ATCC 25923 biofilm formation inhibition was conducted by safranin staining method. At tested concentrations of 0.18, 0.09, 0.045 μg/mL (concentrations much lower than MIC value determined on planktonic strain) the novel pyrrolomycin derivative IV resulted effective as biofilm inhibitor showing inhibition percentages ranging from 56.5 to 29% against S.aureus ATCC 25923. We are investigating if sortase A which is responsible for the anchoring of surface proteins to Gram positive cell wall, could be the rational target of pyrrolomycins. The surface proteins play pivotal roles in the adhesion to host’s tissues, and the evasion of host-immune responses, moreover they facilitate attachment on biological and abiotic surfaces in the first steps of biofilm formation. It has been observed that inhibition of sortase A by different chemicals resulted in decrease of virulence and staphylococcal biofilm formation. A molecular modeling study conducted by using a crystal structure of sortase A, recovered from protein data bank, and by studying docking properties of a known sortase A inhibitor and of pyrrolomycins, is in progress. In vitro experiments on sortase inhibition activity are needed to confirm the computational results