Synergistic effects of short peptides and antibiotics against bacterial and fungal strains

Abstract

There is a rising tide of concern about the antibiotic resistance issue. To reduce the possibility of antibiotic‐resistant infections, a new generation of antimicrobials must be developed. Antimicrobial peptides are potential alternatives to antibiotics that can be used alone or together with conventional antibiotics to combat antimicrobial resistance. In this work, lead compounds LP‐23, DP‐23, SA4, and SPO from previously published studies were synthesized by solid‐phase peptide synthesis and their antimicrobial evaluation was carried out against various bacterial and fungal strains. Peptide combinations with antibiotics were evaluated by using the checkerboard method and their minimal inhibitory concentration (MIC) in combination was calculated by using the fractional inhibitory concentration (FIC) index. Cytotoxicity evaluations of these peptides further confirmed their selectivity toward microbial cells. Based on the FIC values, LP‐23, DP‐23, and SPO demonstrated synergy in combination with gentamicin against a gentamicin‐resistant clinical isolate of Escherichia coli. For Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium, seven combinations exhibited synergistic effects between peptide/peptoids and the tested antibiotics. Additionally, almost all the combinations of peptides/peptoids with amphotericin B and fluconazole also showed effective synergy against Aspergillus niger and Aspergillus flavus. The synergy found between LP‐23, DP‐23, SA4, and SPO with the selected antibiotics may have the potential to be used as a combination therapy against various microbial infections.

Synergistic action of synthetic peptides and amphotericin B causes disruption of the plasma membrane and cell wall in Candida albicans

“…In 2023 [ 29 ] the lead compounds LP-23, DP-23, SA4, and SPO, synthesized via solid-phase peptide synthesis, exhibited synergistic effects when combined with specific antibiotics. This synergy was observed against a spectrum of bacterial and fungal strains, underscoring the potential of these compounds in enhancing antimicrobial efficacy.…”

Various Biomimetics as Antifungals

“…One of the effective solutions to this problem today is the combined use of various antifungals. Such possible combinations can include various traditional antifungal agents and AFPs (Table 6) [18,37,45,57,67,[128][129][130][131][132][133][134][135][136][137][138][139][140]. Such combinations make it possible to joint different mechanisms (targets) of the effects of antifungals and significantly decrease their toxicity by improving the effectiveness of the action and reducing the doses applied in comparison with individual substances.…”

“…The use of mimetic peptides DP-23 (short lipopeptide) and SPO (N-substituted polyglycine) in combination with fluconazole provided a synergistic effect on A. niger and A. flavus cells [18].…”

“…The antifungal effect of these compounds and materials is not limited to the destruction of the cell wall and membranes of fungi, but affects their various metabolically important pathways, growth and spore formation [15][16][17]. Of great interest is the possible synergistic effect among such biomimetics with antifungal drugs, which allows to reduce the doses of individual substances used [18,19].…”

Various Biomimetics, Including Peptides as Antifungals

“…The antifungal effect of these compounds and materials is not limited to the destruction of the cell wall and membranes of fungi but affects their various metabolically important pathways, growth and spore formation [16][17][18]. Of great interest is the possible synergistic effect among such biomimetics with antifungal drugs, which allows for a reduction in the doses of individual substances used [19,20].…”