The antimicrobial activity of Cbf-K16 against MRSA was enhanced by β-lactamantibiotics through cell wall non-integrity.
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.
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Bo
B
Li
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Wei
W
Kang
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Hanhan
H
Liu
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Yanrong
Y
Wang
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Changzhong
C
Yu
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Xinyi
X
Zhu
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
Jie
J
Dou
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
Haibo
H
Cai
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. cl_zhou@cpu.edu.cn.
Changlin
C
Zhou
D000595:Amino Acid Sequence; D000667:Ampicillin / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000378:metabolism; D016470:Bacteremia / Q000188:drug therapy / Q000378:metabolism; D054804:Cathelicidins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D002442:Ceftazidime / Q000008:administration & dosage* / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests / Q000379:methods
D000890:Anti-Infective Agents; D054804:Cathelicidins; C582656:Cbf-K16 peptide; D000667:Ampicillin; D002442:Ceftazidime
Ampicillin; Antimicrobial activity; Cbf-K16; Ceftazidime; MRSA; Synergistic effect