EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Bacterial efflux pump modulators prevent bacterial growth in macrophages and under broth conditions that mimic the host environment.
ジャーナル・号・ページ	mBio, Vol. 14, Issue 6, Page e0249223, Year 2023
掲載日	2023年11月3日
著者	Samual C Allgood / Chih-Chia Su / Amy L Crooks / Christian T Meyer / Bojun Zhou / Meredith D Betterton / Michael R Barbachyn / Edward W Yu / Corrella S Detweiler /
PubMed 要旨	Bacterial efflux pumps are critical for resistance to antibiotics and for virulence. We previously identified small molecules that inhibit efflux pumps (efflux pump modulators, EPMs) and prevent ...Bacterial efflux pumps are critical for resistance to antibiotics and for virulence. We previously identified small molecules that inhibit efflux pumps (efflux pump modulators, EPMs) and prevent pathogen replication in host cells. Here, we used medicinal chemistry to increase the activity of the EPMs against pathogens in cells into the nanomolar range. We show by cryo-electron microscopy that these EPMs bind an efflux pump subunit. In broth culture, the EPMs increase the potency (activity), but not the efficacy (maximum effect), of antibiotics. We also found that bacterial exposure to the EPMs appear to enable the accumulation of a toxic metabolite that would otherwise be exported by efflux pumps. Thus, inhibitors of bacterial efflux pumps could interfere with infection not only by potentiating antibiotics, but also by allowing toxic waste products to accumulate within bacteria, providing an explanation for why efflux pumps are needed for virulence in the absence of antibiotics.
リンク	mBio / PubMed:37921493 / PubMed Central
手法	EM (単粒子)
解像度	2.44 - 2.71 Å
構造データ	44496 9bfh EMDB-44496, PDB-9bfh: Cryo-EM co-structure of AcrB with the CU032 efflux pump inhibitor 手法: EM (単粒子) / 解像度: 2.62 Å 44500 9bfm EMDB-44500, PDB-9bfm: Cryo-EM co-structure of AcrB with the EPM35 efflux pump inhibitor 手法: EM (単粒子) / 解像度: 2.71 Å 44501 9bfn EMDB-44501, PDB-9bfn: Cryo-EM co-structure of AcrB with the CU232 efflux pump inhibitor 手法: EM (単粒子) / 解像度: 2.71 Å 44506 9bft EMDB-44506, PDB-9bft: Cryo-EM co-structure of AcrB with CU244 手法: EM (単粒子) / 解像度: 2.44 Å
化合物	PDB-1an8: CRYSTAL STRUCTURE OF THE STREPTOCOCCAL SUPERANTIGEN SPE-C ChemComp-HOH: WATER PDB-1aon: CRYSTAL STRUCTURE OF THE ASYMMETRIC CHAPERONIN COMPLEX GROEL/GROES/(ADP)7 ChemComp-3PE: 1,2-Distearoyl-sn-glycerophosphoethanolamine / DSPE / リン脂質YM PDB-1aoe: CANDIDA ALBICANS DIHYDROFOLATE REDUCTASE COMPLEXED WITH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NADPH) AND 1,3-DIAMINO-7-(1-ETHYEPROPYE)-7H-PYRRALO-[3,2-F]QUINAZOLINE (GW345) PDB-1aof*: CYTOCHROME CD1 NITRITE REDUCTASE, REDUCED FORM
由来	Homo sapiens (ヒト) escherichia coli k-12 (大腸菌)
キーワード	TRANSLOCASE / AcrB Multidrug Efflux Pump