The study of antistaphylococcal potential of Omiganan and retro-Omiganan under flow conditions

Abstract

Abstract Staphylococcus aureus is considered as one of the leading pathogens responsible for infections in humans and animals. The heterogeneous nature of diseases caused by these bacteria is due to occurrence of multiple strains, differentiated by several mechanisms of antibiotic resistance and virulence factors. One of these is the ability to form biofilm. Biofilm-associated bacteria exhibit a different phenotype that protects them from external factors such as activity of immune system or antimicrobial substances. Moreover, it was shown that in majority of persistent and recurrent infections is associated with the presence of the biofilm. Antimicrobial peptides (AMPs) are compounds widely distributed in nature as a key component of non-specific immunity of organisms with a wide spectrum of antimicrobial activity. Their amino acid-based structure as well as approaches of chemical synthesis indicate that AMPs provide an excellent matrix for the development of new antimicrobials. Omiganan an analog of Indolicidin, is a peptide derived from bovine neutrophil granules which was found to exhibit high antistaphylococcal and antibiofilm potential. Furthermore, its analog with a reversed sequence (retro-Omiganan) was found to display enhanced activity against a variety of pathogens. The aim of this study was to investigate the activity of both compounds against S. aureus biofilm under flow conditions. The advantage of this approach was that it offered the opportunity to form and characterize the biofilm under more controlled conditions. To do this, unique flow cells made of polydimethylsiloxane (PDMS) were developed. The activity against pre-formed biofilm as well AMPs-treated bacteria was measured. Also, incorporation of Omiganan and retro-Omiganan into the channels was conducted to learn whether or not it would inhibit the development of biofilm. The results of the microbiological tests ultimately confirmed the high potential of the Omiganan and its retro analog. Moreover, the developed methodology allows implementation of the studies under flow conditions to other compounds.