Antibacterial activity of human defensins againstStaphylococcus aureusandEscherichia coli

Abstract

Background The global problem of antibiotic resistance requires the search for and development of new methods of treatment. One of the promising strategies is the use of low doses of antimicrobial peptides, in particular, human defensins HNP-1, hBD-1, and hBD-3, in combination with antibacterial drugs already used in clinical practice. This approach may be used to increase the effectiveness of conventional antibiotics. However, this requires thorough study of the effectiveness of defensins in combination with antibiotics against a large number of bacterial strains with known phenotypes of antibiotic resistance. The aim of this work was to study the antibacterial effect of HNP-1, hBD-1 and hBD-3 in combination with rifampicin or amikacin against clinical isolates of Staphylococcus aureus (n = 27) and Escherichia coli (n = 24) collected from hospitalized patients. Methods The standard checkerboard assay was used to determine minimum inhibitory concentrations (MICs) of antimicrobials. The combined microbicidal effects of two substances (defensin + conventional antibiotic) were assessed by the fractional inhibitory concentration index (FICI). Results The highest anti-staphylococcal activity (including methicillin-resistant strains) among defensins was demonstrated by hBD-3 that had MIC of 1 (0.5–4) mg/L (hereinafter, MIC values are presented as median and interquartile range). The MIC of HNP-1 against S. aureus was 4 (2–8) mg/L; the MIC of hBD-1 was 8 (4–8) mg/L. Against E. coli, the most effective was also found to be hBD-3 that had MIC of 4 (4–8) mg/L; the MIC of HNP-1 was 12 (4–32) mg/L. The combinations of HNP-1 + rifampicin and hBD-3 + rifampicin demonstrated synergistic effects against S. aureus. Against E. coli, combinations of HNP-1 + amikacin and hBD-3 + amikacin also showed synergy of action.

Promising role of defensins peptides as therapeutics to combat against viral infection

“…Among the six kingdoms (archaea, microbes, protists, fungi, animals, and plants), more than 3000 AMPs have been recognised until now [ 133 ]. Among AMPs of incredible intrigued are human defensins: human beta-defensin-1 (hBD-1), human neutrophil peptide-1 (HNP-1), and human beta-defensin-3 (hBD-3), since they have a wide range of antimicrobial action [ 134 , 135 ].…”

“…Although, insertion of native AMPs into clinical use as a monotherapy for bacterial diseases features several constraints: for instance, synthesis expense, cytotoxicity for macroorganism, immunogenicity, hemolytic activity, and pharmacokinetic specifics [ 139 , 140 ]. Other methods should be used to understand these issues: such as modifying provincial AMPs or designing primitive antimicrobial peptides [ 139 ] and utilising local AMPs at minimum dosages in combination with conventional antimicrobial synthetic drugs [ 135 , 141 ].…”

Mass Spectrometry (Imaging) for Detection and Identification of Cyclic AMPs: Focus on Human Neutrophil Peptides (HNPs)

“…HNP1 has even been considered as a lead compound in combating methicillin-resistant strains of Staphylococcus aureus (MRSA). When applied together antibiotics, the HNPs show a synergistic effect towards different MRSA isolates, paving the way for a new therapeutic approach to overcome the increasing antibiotic resistance [42].…”

Host Defense Peptide-Mimicking Polymers and Polymeric-Brush-Tethered Host Defense Peptides: Recent Developments, Limitations, and Potential Success

“…Second, many HDPs have recently been shown to synergize with conventional antibiotics; this provides another path for their practical use in addressing bacterial resistance mechanisms [150][151][152]. For example, peptides can increase the intracellular concentration of antibiotics by increasing their cellular uptake based on several studies performed against planktonic bacteria [153][154][155]. Furthermore, this synergistic or additive effect has also been demonstrated to enhance the antibiofilm activity of HDP/antibiotic combinations [156][157][158].…”