ABSTRACT
The purpose of the work was to investigate the impact of sodium chloride (NaCl) on the antimicrobial efficacy of ceragenins (CSAs) and antimicrobial peptides (AMPs) against bacterial and fungal pathogens associated with cystic fibrosis (CF) lung infections. CF-associated bacterial (Pseudomonas aeruginosa, Ochrobactrum spp., and Staphylococcus aureus), and fungal pathogens (Candida albicans, and Candida tropicalis) were used as target organisms for ceragenins (CSA-13 and CSA-131) and AMPs (LL-37 and omiganan). Susceptibility to the tested compounds was assessed using minimal inhibitory concentrations (MICs) and bactericidal concentrations (MBCs), as well as by colony counting assays in CF sputum samples supplemented with various concentrations of NaCl. Our results demonstrated that ceragenins exhibit potent antimicrobial activity in CF sputum regardless of the NaCl concentration when compared to LL-37 and omiganan. Given the broad-spectrum antimicrobial activity of ceragenins in the microenvironments mimicking the airways of CF patients, ceragenins might be promising agents in managing CF disease.
ABSTRACT
Antimicrobial resistance is a major and growing global problem and new approaches to combat infections caused by antibiotic resistant bacterial strains are needed. In recent years, increasing attention has been paid to nanomedicine, which has great potential in the development of controlled systems for delivering drugs to specific sites and targeting specific cells, such as pathogenic microbes. There is continued interest in metallic nanoparticles and nanosystems based on metallic nanoparticles containing antimicrobial agents attached to their surface (core shell nanosystems), which offer unique properties, such as the ability to overcome microbial resistance, enhancing antimicrobial activity against both planktonic and biofilm embedded microorganisms, reducing cell toxicity and the possibility of reducing the dosage of antimicrobials. The current review presents the synergistic interactions within metallic nanoparticles by functionalizing their surface with appropriate agents, defining the core structure of metallic nanoparticles and their use in combination therapy to fight infections. Various approaches to modulate the biocompatibility of metallic nanoparticles to control their toxicity in future medical applications are also discussed, as well as their ability to induce resistance and their effects on the host microbiome.