PXD053342

PXD053342 is an original dataset announced via ProteomeXchange.

Title	A synthetic antibiotic class with a deeply-optimized design for overcoming bacterial resistance
Description	The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.
HostingRepository	iProX
AnnounceDate	2024-06-24
AnnouncementXML	Submission_2024-06-24_01:43:39.232.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jin Feng
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-24 01:42:12	ID requested
⏵ 1	2024-06-24 01:43:39	announced

Dataset with its publication pending

submitter keyword: antibiotic resistance

structure-based drug design

arcB

bacteria

drug

target.

Jin Feng
contact affiliation	Huazhong Agricultural University
contact email	fengjin@webmail.hzau.edu.cn
lab head
Jin Feng
contact affiliation	Huazhong Agricultural University
contact email	fengjin@webmail.hzau.edu.cn
dataset submitter

iProX dataset URI