Discovery of novel BfmR inhibitors restoring carbapenem susceptibility against carbapenem-resistant Acinetobacter baumannii by structure-based virtual screening and biological evaluation DOI Creative Commons
Yue Yao, Tailong Lei, Junbo Gao

и другие.

Emerging Microbes & Infections, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 28, 2024

The emergence and spread of Acinetobacter baumannii pose a severe threat to public health, highlighting the urgent need for next generation therapeutics due its increasing resistance existing antibiotics. BfmR, response regulator modulating virulence antimicrobial resistance, shows promising potential as novel target. Developing BfmR inhibitors may propel new therapeutic direction intractable infection resistant strains. In this study, we conducted structure-based hierarchical virtual screening pipeline combining molecular docking, dynamics simulation MM/GBSA calculation sift Specs chemical library finally discover three inhibitors. hits can reduce MIC meropenem carbapenem-resistant (CRAB) strain ZJ06. Similar knockout strain, Cmp-98 was demonstrated downregulate expression K locus genes, indicating it inhibitor. Bacteria underwent harmful morphological changes after treatment with these Molecular simulations found that all tend dynamically bind different positions phosphorylation site BfmR. Wherein identified inhibitory binding cleft, beside possible activated cleft at edge site. Restraining ligand poses help exerting effects. This study reports group new-scaffold inhibitors, offering insights antibiotic against CRAB.

Язык: Английский

Jelleine-I Membrane Interaction-related Biological Properties and Antimicrobial Activity against MDR, XDR, and PDR-Acinetobacter baumannii Clinical Isolates DOI Creative Commons
Adrielle Pieve de Castro, Júlio César Moreira Brito,

Wanderson Aparecido Brandão Candido

и другие.

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Emerging bacterial infections pose a serious threat to human health. Acinetobacter baumannii is particular concern due its antimicrobial resistance phenotypes, especially carbapenems. In this context, peptides appear as promising class. Jelleine-I peptide identified from the royal jelly Apis mellifera bee, which has demonstrated significant antibacterial effects against various microorganisms. This study aimed characterize activity of jelleine-I clinical isolates A. resistant carbapenems (CRAB) and with different in addition investigating peptide–membrane interaction biomimetic media. Microbiological assays performed MIC values 8–16 μM were observed. Biophysical studies on mimetic membrane show possible disruption organization phospholipid bilayer. The affinity promoted by entropic enthalpic contributions suggests that main action occurs membrane. addition, negligible hemolytic toxicity VERO HaCaT cells reveal potential novel agent, microorganisms exhibit high diverse resistance, such baumannii.

Язык: Английский

Процитировано

0
Discovery of novel BfmR inhibitors restoring carbapenem susceptibility against carbapenem-resistant Acinetobacter baumannii by structure-based virtual screening and biological evaluation DOI Creative Commons
Yue Yao, Tailong Lei, Junbo Gao

и другие.

Emerging Microbes & Infections, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 28, 2024

The emergence and spread of Acinetobacter baumannii pose a severe threat to public health, highlighting the urgent need for next generation therapeutics due its increasing resistance existing antibiotics. BfmR, response regulator modulating virulence antimicrobial resistance, shows promising potential as novel target. Developing BfmR inhibitors may propel new therapeutic direction intractable infection resistant strains. In this study, we conducted structure-based hierarchical virtual screening pipeline combining molecular docking, dynamics simulation MM/GBSA calculation sift Specs chemical library finally discover three inhibitors. hits can reduce MIC meropenem carbapenem-resistant (CRAB) strain ZJ06. Similar knockout strain, Cmp-98 was demonstrated downregulate expression K locus genes, indicating it inhibitor. Bacteria underwent harmful morphological changes after treatment with these Molecular simulations found that all tend dynamically bind different positions phosphorylation site BfmR. Wherein identified inhibitory binding cleft, beside possible activated cleft at edge site. Restraining ligand poses help exerting effects. This study reports group new-scaffold inhibitors, offering insights antibiotic against CRAB.

Язык: Английский

Процитировано

1