Antimikrobik etkili katyonik peptitlerin tek başına ve kombinasyon halindeki etkilerinin araştırılması

Günümüzde, antibiyotiklere karşı görülen direncin oldukça yüksek düzeylere ulaşması, araştırmacıları yeni antimikrobik etkili kaynakların arayışına yöneltmiştir. Yakın gelecekte kullanılması düşünülen bu maddeler arasında en fazla umut vaat eden grup antimikrobik etkili katyonik peptitlerdir. Çalışmamızda farklı yapılardaki katyonik peptitlerden kolistin metansülfonat (kolimisin), mellitin ve nisinin hastalardan infeksiyon etkeni olarak izole edilen Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, metisiline duyarlı Staphylococcus aureus (MSSA), metisiline dirençli S.aureus (MRSA) ve Enterococcus faecalis suşları üzerine tek başına ve sık kullanılan antibiyotiklerden amikasin, seftazidim, imipenem, siprofloksasin, ampisilin, eritromisin ve vankomisinle kombinasyon halindeki in-vitro etkileri araştırılmıştır. Mikrodilüsyon yöntemi kullanılarak yapılan çalışmalarda elde edilen bulgulara göre Gram negatif bakterilerden P.aeruginosa, E.coli ve K.pneumoniae suşlarına karşı kolistin metansülfonatın MİK90 değerleri sırasıyla 2 µg/ml, 0.5 µg/ml ve 1 µg/ml; mellitinin ise >64 µg/ml, 8 µg/ml ve 32 µg/ml; Gram pozitif bakterilerden MSSA, MRSA ve E.faecalis suşlarına karşı mellitinin MİK90 değerleri sırasıyla 8 µg/ml, 8 µg/ml ve 8 µg/ml; nisinin ise 16 µg/ml, 16 µg/ml ve 16 µg/ml olarak bulunmuştur. Antimikrobik etkili katyonik peptitlere ait MBK değerleri genellikle MİK değerlerine eşit ya da iki katı olarak bulunmuştur. Kombinasyon çalışmalarında en fazla sinerjist etki kolistin metansülfonat-siprofloksasin kombinasyonu ile (% 54) P.aeruginosa, kolistin metansülfonat-imipenem kombinasyonu ile (sırasıyla % 50 ve % 54) E.coli ve K.pneumoniae, nisin-imipenem kombinasyonu ile (% 67) MRSA, nisin-ampisilin kombinasyonu ile (sırasıyla % 67 ve % 47) MSSA ve E.faecalis suşlarına karşı elde edilmiş, denenen kombinasyonların hiçbirinde antagonist etki görülmemiştir.

Anahtar Kelimeler:

Melitten, Nisin, Antimikrobiyal katyonik peptidler, Anti-bakteriyel ajanlar, Kolistin

In-vitro activities of antimicrobial cationic peptides alone and in combination with antibiotics

Since levels of antibiotic resistance have been increasing at an alarming rate worldwide, cationic peptides seems to be the most preferable class of antimicrobial substances in the near future as therapeutic agents. In this study, the in vitro activities of antimicrobial cationic peptides colistin methanesulphonate (colimycin), mellitin and nisin alone and in combination with frequently used antibiotics such as amikacin, ceftazidime, imipenem, ciprofloxacin, ampicillin, erythromycin and vancomycin were assessed in clinical isolates of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S.aureus (MRSA) and Enterococcus faecalis. Using the microdilution method, MIC90 values of cationic peptides against Gram negative P.aeruginosa, E.coli and K. pneumoniae strains were 2 µg/ml, 0.5 µg/ml and 1 µg/ml with colistin methanesulphonate, >64 µg/ml, 8 µg/ml and 32 µg/ml with mellitin, respectively. Against Gram positive MSSA, MRSA and E.faecalis strains MIC90 values were 8 µg/ml, 8 µg/ml and 8 µg/ml with mellitin, 16 µg/ml, 16 µg/ml and 16 µg/ml with nisin, respectively. The MBC values were generally equal or two times greater than those of MIC values. In combination studies synergistic interactions were most requent with colistin methanesulphonate-ciprofloxacin combination against P.aeruginosa (54 %); with colistin methanesulphonateimipenem combination against E.coli and K.pneumoniae (50 % and 54 %, respectively); with nisin-imipenem combination against MRSA (67 %) and with nisin-ampicillin combination against MSSA and E.faecalis (67 % and 47 %, respectively). None of the combinations showed antagonistic effect.

Keywords:

Melitten, Nisin, Antimicrobial Cationic Peptides, Anti-Bacterial Agents, Colistin,

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