Antimicrobial peptides (AMPs) are promising alternatives to antibiotics, but discovering potent, low-toxicity candidates and improving their delivery remain challenging. In this study, novel AMPs were identified by constructing and screening a synthetic random peptide library using a bacterial surface display system. Rational design generated derivative peptides, among which WP-4 and WP-6 showed high antimicrobial activity, good biocompatibility, rapid bactericidal effects, and low propensity for resistance development. WP-6 also showed good in vivo therapeutic potency in a murine Escherichia coli systemic infection model. Mechanistic studies indicated that WP-4 and WP-6 target bacterial cell membranes, disrupt the proton motive force, and induce excessive reactive oxygen species accumulation. To further improve their activity and in vivo performance, WP-4 and WP-6 were encapsulated within zeolitic imidazolate framework-8, yielding improved antimicrobial activity and proteolytic resistance. These nanoparticles exhibited superior therapeutic efficacy in a Streptococcus suis-induced arthritis model. Our study identified potent AMPs with promising therapeutic potential.
Shuai-Yang Wang, S.-S. Wang, Xiu-Jian Liu et al.· Journal of Medicinal Chemist...· 0 citations
Anthelmintic resistance constitutes a global threat to the control of parasitic nematodes. Current research has primarily focused on parasite-intrinsic genetic mechanisms, while the contribution of the symbiotic microbial community remains a key knowledge gap. Here, we report that ivermectin (IVM) resistance in the gastrointestinal nematode Haemonchus contortus is associated with the abundance of the bacterium Stenotrophomonas maltophilia. A representative strain, designated SM1, was isolated from resistant populations, and its abundance was associated with the resistant phenotype. Depletion of SM1 increased larval susceptibility to IVM, whereas reintroduction of the bacterium partially enhanced IVM tolerance. Metabolic analysis indicated that SM1 converts IVM into demethylated and oxo-derivatives (M1, M4, and M7). Using in silico analysis, the putative cytochrome P450 monooxygenase (Cmp08160) with a possible participation in IVM biotransformation was identified. Collectively, these findings suggest that symbiotic bacteria can influence IVM susceptibility in H. contortus and highlight the relevance of considering host–microbiota interactions in studies of anthelmintic resistance.
Si-Min Wu, Chun-Qun Wang, Jun-Cheng Li et al.· International Journal for Pa...· 0 citations
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