Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates
ANTIBIOTICS-BASEL
Authors: Zai, Yu; Ying, Yuan; Ye, Zhuming; Zhou, Mei; Ma, Chengbang; Shi, Zhanzhong; Chen, Xiaoling; Xi, Xinping; Chen, Tianbao; Wang, Lei
Abstract
DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala(1) and Trp(3) remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistantStaphylococcus aureus(MRSA) andKlebsiella pneumoniaeusing theGalleria mellonellalarva model and displayed synergistic activities with gentamicin against carbapenem-resistantK. pneumoniaestrains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.
Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing
NATURE COMMUNICATIONS
Authors: Qiao, Yuqian; Liu, Xiangmei; Li, Bo; Han, Yong; Zheng, Yufeng; Yeung, Kelvin Wai Kwok; Li, Changyi; Cui, Zhenduo; Liang, Yanqin; Li, Zhaoyang; Zhu, Shengli; Wang, Xianbao; Wu, Shuilin
Abstract
Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.
COA
Publication 
Loading ......
