Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa.
Geitani. Regina R; Ayoub Moubareck. Carole C; Touqui. Lhousseine L; Karam Sarkis. Dolla D
Key Findings
- LL‑37 (and a synthetic peptide called CAMA) rapidly reduces bacterial counts of MRSA and multidrug‑resistant P. aeruginosa within 2 hours.
- Combining LL‑37 with colistin or imipenem cuts the needed antibiotic dose by up to 8‑fold and 4‑fold respectively.
- LL‑37 shows no significant toxicity to human lung epithelial cells in vitro and induces only transient, low‑level bacterial resistance.
Practical Outcomes
- For DIY health enthusiasts, LL‑37 looks promising as a fast‑acting antimicrobial that could boost existing antibiotics, especially for skin or airway infections. However, the data are limited to lab cultures, so safe dosing, delivery methods, and regulatory issues need careful consideration before real‑world use.
Summary
The human peptide LL‑37 kills both regular and drug‑resistant Staph aureus and Pseudomonas bacteria very quickly in lab tests, works even better when paired with some antibiotics, doesn’t hurt human lung cells, and bacteria only develop a tiny, temporary resistance to it.
Abstract
Methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa are becoming difficult to treat with antibiotics whereas Cationic Antimicrobial Peptides (CAMPs) represent promising alternatives. The effects of four CAMPs (LL-37: human cathelicidin, CAMA: cecropin(1-7)-melittin A(2-9) amide, magainin-II and nisin) were investigated against clinical and laboratory S. aureus (n = 10) and P. aeruginosa (n = 11) isolates either susceptible or resistant to antibiotics. Minimal Inhibitory Concentrations (MICs), Minimal Bactericidal Concentrations (MBCs), and bacterial survival rates (2 h post-treatment) were determined by microbroth dilution. The antipseudomonal effects of the antibiotics colistin or imipenem combined to LL-37 or CAMA were also studied. The toxicity of CAMPs used alone and in combination with antibiotics was evaluated on two human lung epithelial cell lines by determining the quantity of released cytoplasmic lactate dehydrogenase (LDH). Attempts to induce bacterial resistance to gentamicin, LL-37 or CAMA were also performed. The results revealed the rapid antibacterial effect of LL-37 and CAMA against both antibiotic susceptible and resistant strains with almost a total reduction in bacterial count 2 h post-treatment. Magainin-II and nisin were less active against tested strains. When antibiotics were combined with LL-37 or CAMA, MICs of colistin decreased up to eight-fold and MICs of imipenem decreased up to four-fold. Cytotoxicity assays revealed non-significant LDH-release suggesting no cell damage in all experiments. Induction of bacterial resistance to LL-37 was transient, tardive and much lower than that to gentamicin and induction of resistance to CAMA was not observed. This study showed the potent and rapid antibacterial activity of CAMPs on both laboratory and clinical isolates of S. aureus and P. aeruginosa either susceptible or resistant to antibiotics. Most importantly, CAMPs synergized the efficacy of antibiotics, had non toxic effects on human cells and were associated with transient and low levels of induced resistance.
Study Information
pubmed
2019
2019-03-08T00:00:00.000Z
10.1186/s12866-019-1416-8
99
46