Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Microbiology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12866-019-1416-8 |
| _version_ | 1818509717163474944 |
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| author | Regina Geitani Carole Ayoub Moubareck Lhousseine Touqui Dolla Karam Sarkis |
| author_facet | Regina Geitani Carole Ayoub Moubareck Lhousseine Touqui Dolla Karam Sarkis |
| author_sort | Regina Geitani |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusion 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. |
| first_indexed | 2024-12-10T22:49:14Z |
| format | Article |
| id | doaj.art-0020c4c997ee41fe873fb2f8f6780aa7 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-10T22:49:14Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-0020c4c997ee41fe873fb2f8f6780aa72022-12-22T01:30:29ZengBMCBMC Microbiology1471-21802019-03-0119111210.1186/s12866-019-1416-8Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosaRegina Geitani0Carole Ayoub Moubareck1Lhousseine Touqui2Dolla Karam Sarkis3Microbiology Laboratory, School of Pharmacy, Saint Joseph UniversityMicrobiology Laboratory, School of Pharmacy, Saint Joseph UniversityUnité de Mucoviscidose et Bronchopathies Chroniques, Institut Pasteur/Faculté de Médecine CochinMicrobiology Laboratory, School of Pharmacy, Saint Joseph UniversityAbstract Background 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12866-019-1416-8Methicillin-resistant Staphylococcus aureusMultidrug-resistant Pseudomonas aeruginosaCationic antimicrobial peptidesAlternative to antibiotics |
| spellingShingle | Regina Geitani Carole Ayoub Moubareck Lhousseine Touqui Dolla Karam Sarkis Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa BMC Microbiology Methicillin-resistant Staphylococcus aureus Multidrug-resistant Pseudomonas aeruginosa Cationic antimicrobial peptides Alternative to antibiotics |
| title | Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa |
| title_full | Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa |
| title_fullStr | Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa |
| title_full_unstemmed | Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa |
| title_short | Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa |
| title_sort | cationic antimicrobial peptides alternatives and or adjuvants to antibiotics active against methicillin resistant staphylococcus aureus and multidrug resistant pseudomonas aeruginosa |
| topic | Methicillin-resistant Staphylococcus aureus Multidrug-resistant Pseudomonas aeruginosa Cationic antimicrobial peptides Alternative to antibiotics |
| url | http://link.springer.com/article/10.1186/s12866-019-1416-8 |
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