Fengjing Jia,Yi Zhang,Jiayi Wang,Jinxiu Peng,Ping Zhao,Lishi Zhang,Haiyan Yao,Jingman Ni,Kairong Wang
Antimicrobial peptides (AMPs) are believed to be a promising class of antimicrobial agents against bacteria and fungi. To promote the clinical use of AMPs, their antimicrobial activity and susceptibility to protease degradation should be further improved. The antimicrobial peptide Jelleine-I was originally isolated from the royal jelly of honeybees ( Apis mellifera ) with a short sequence of PFKLSLHL-NH 2 (953.24 Da). Here, a series of halogenated derivatives of the antimicrobial peptide Jelleine-I were designed and synthesized. The results showed that the in vitro antimicrobial activity, antibiofilm activity and in vivo antimicrobial efficacy were enhanced 1-8-fold after halogenation. Additionally, the proteolytic stability of Jelleine-I was improved 10-100-fold by halogenation. Meanwhile, the halogenated derivatives retained negligible hemolytic activity and cytotoxicity. Among these derivatives, the antimicrobial activity and antibiofilm activity of chlorine-Jelleine-I (Cl-J-I), bromine-Jelleine-I (Br-J-I), and iodine-Jelleine-I (I-J-I) were better than those of fluorine-Jelleine-I (F-J-I). The stabilities of Br-J-I and I-J-I against the degradation of enzymes and the serum were better than those of F-J-I and Cl-J-I. In conclusion, this study may offer a useful strategy to enhance antimicrobial efficacy and proteolytic stability by halogenation. The halogenated derivatives Cl-J-I, Br-J-I and I-J-I may be considered as potential antimicrobial agents against microbial infection.
Fengjing Jia,Qun Yu,Ruolei Wang,Ling Zhao,Fuwen Yuan,Haidong Guo,Yunhui Shen,Feng He
Colorectal cancer (CRC) is a major health burden worldwide due to its high morbidity, mortality, and complex etiology.Fusobacterium nucleatum(Fn), a Gram-negative anaerobe found in 30% of CRC patients, promotes CRC carcinogenesis, metastasis, and chemoresistance. Effective antimicrobial treatment is an unmet need for the rising CRC burden. Antimicrobial peptides (AMPs) represent a new class of antimicrobial drugs. In our previous study, we did the structure-activity study of Jelleine-I (J-I) and identified several halogenated J-I derivatives Cl-J-I, Br-J-I, and I-J-I. To determine whether those J-I derivatives can be a new therapy for bacterial-associated CRC, here we tested the antibacterial activities of these AMPs againstFnand their effects on CRC development. We found that Br-J-I showed the highest anti-Fnactivity and Br-J-I may target membrane-associated FadA forFnmembrane disruption. More importantly,Fnpromoted the growth of CRC cells-derived xenograft tumors. Br-J-I suppressedFnload, colon inflammation, andFn-induced CRC growth. Of note, Br-J-I induced better anti-CRC effects than common antibiotic metronidazole and Br-J-I sensitized the cancer-killing effect of chemotherapy drug 5-fluorouracil. These results suggest that Br-J-I could be considered as an adjunctive agent for CRC treatment and AMPs-based combination treatment is a new strategy for CRC in the future.Keywords:colorectal cancer;fusobacterium nucleatum;antimicrobial peptides;adjunctive therapy;antimicrobial treatment
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