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KMID : 0043320160390070978
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Archives of Pharmacal Research
2016 Volume.39 No. 7 p.978 ~ p.988
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The antimicrobial activity of Cbf-K16 against MRSA was enhanced by β-lactamantibiotics through cell wall non-integrity
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Li Bo
Kang Wei
Liu Hanhan
Wang Yanrong
Yu Changzhong
Zhu Xinyi
Dou Jie
Cai Haibo
Zhou Changlin
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Abstract
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Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important pathogens both in health care and in community-onset infections. Cbf-K16, a cathelicidin-like antimicrobial peptide, presented broad antimicrobial activity during our previous studies. We evaluated the potential for synergy of Cbf-K16 with ceftazidime/ampicilin against MRSA, which was resistant to these two antibiotics with the minimum inhibitory concentration more than 64 μg/ml. The combinations showed a synergistic effect by a checkerboard assay with a fractional inhibitory concentration index ≤0.5. The killing curves of the combination treatment against MRSA showed that CFU counts decreased rapidly within 4 h by almost five logs, while single medication groups and the control group exhibited little inhibitory effect. In addition, in a mice bacteremia model, studies indicated that the combination treatment significantly prolonged the survival time of mice infected with MRSA, with a death protection rate of 80 %. Flow cytometry analysis and transmission electron microscopy indicated that combination-treated MRSA was completely ruptured with the cellular contents leaked out. The synergistic effect showed that Cbf-K16 selectively killed cells with non-integrity induced by cell wall inhibition antibiotics, suggesting that Cbf-K16 is a potential therapeutic agent and adjuvant for antimicrobial chemotherapy.
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KEYWORD
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Cbf-K16, Antimicrobial activity, Ceftazidime, Ampicillin, MRSA, Synergistic effect
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