Antimicrobial Activities of Twenty Lysine-Peptoid Hybrids against Clinically Relevant Bacteria and Fungi

Abstract

Background: This paper describes the antimicrobial activities of 20 lysine-peptoid hybrids against a selection of clinically relevant bacteria and fungi. Methods: Minimal inhibitory concentrations were determined against methicillin-susceptible Staphylococcus aureus (ATCC 29213), methicillin-resistant S. aureus (ATCC 33591), vancomycin-intermediate S. aureus (ATCC 700699 MU50), vancomycin-resistant Enterococcus faecium (ATCC 700221), Pseudomonas aeruginosa (ATCC 27853), Salmonella typhimurium (clinical isolate), Klebsiella pneumoniae (clinical isolate), amphotericin-B-resistant C. albicans (ATCC 200955) and Cryptococcus neoformans (clinical isolate). Results: The lysine-peptoid hybrids proved to be active against all strains tested, except K. pneumoniae. For each susceptible strain, we identified at least 4 lysine-peptoid hybrids showing excellent activity. The most active compounds displayed minimal inhibitory concentrations ranging from ≤1.6 to 6.25 µM. Conclusion: This study demonstrates that lysine-peptoid hybrids show activity against drug-resistant pathogens.

Effect of Systemic Infection Induced by Pseudomonas aeruginosa on the Brain Uptake of Colistin in Mice

“…To reflect the clinical scenario more closely, the impact of systemic infection with P. aeruginosa on the brain uptake of colistin was assessed in a mouse model. The strain of P. aeruginosa selected to induce bacteremia (ATCC 27853) was initially isolated from a patient and has been widely used to determine the antimicrobial activities of various antibiotics (15,35), and therefore, it was considered clinically relevant for this study. It has been shown that inoculation of mice with Escherichia coli and Streptococcus pneumoniae at sepsis-inducing doses leads to BBB disruption, which was demonstrated by brain access of the impermeable horseradish peroxidase (38).…”

In Vitro Activities of LTX-109, a Synthetic Antimicrobial Peptide, against Methicillin-Resistant, Vancomycin-Intermediate, Vancomycin-Resistant, Daptomycin-Nonsusceptible, and Linezolid-Nonsusceptible Staphylococcus aureus

“…Synthetic antimicrobial peptidomimetics (SAMPs) are a new class of drugs with activity against Gram-positive and Gram-negative bacterial species (14). LTX-109 (Lytixar; Lytix Biopharma AS, Oslo, Norway) is one such novel SAMP which rapidly kills bacteria via membrane disruption and has not been associated with cross-resistance to other available drugs.…”

Functional Synergy between Antimicrobial Peptoids and Peptides against Gram-Negative Bacteria

“…The names, sequences, hydrophobicities, antibacterial activities against Gram-negative (E. coli) and Gram-positive (B. subtilis) bacteria, and hemolytic activities of these nine compounds are shown in Table 1 (values in g/ml are provided in Table S1 in the supplemental material). The antibacterial activities are reported as MICs and were determined according to standard CLSI M7-A6 protocols (6); hemolytic activities, determined as previously reported (5), serve as a measure of antimicrobial peptide/peptoid toxicity (9), which is commonly used to optimize antimicrobial peptide/peptoid therapeutic performance (4,5,17,19,(22)(23)(24).…”