English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Antibiotic resistance in  Acinetobacter baumannii  is a major global health threat. New drugs with novel chemical structures are needed to overcome a myriad of resistance mechanisms in  A. baumannii . In this study, we screened an open-source Pathogen Box library for anti- A. baumannii  compounds. Compound MMV675968 (a diaminoquinazoline analog) was the only non-reference compound found to inhibit the growth of all four  A. baumannii  test strains with IC 50  of 0.6–2.7 μM, IC 90  of 0.7–3.9 μM, and MIC of 1.6–10 μM. We showed that MMV675968 targeted  A. baumannii  dihydrofolate reductase ( Ab DHFR) as determined by an  E. coli  surrogate whose growth was dependent on  Ab DHFR function and by an  in vitro  DHFR activity assay. Additionally, chemical scaffolds of DHFR inhibitors that are effective as antibiotics against  A. baumannii  were identified using an  in vitro  DHFR activity assay and  A. baumannii  growth inhibition. MMV675968 was the most potent among DHFR inhibitors tested in inhibiting  A. baumannii  growth. This study shows for the first time that MMV675968 inhibits  A. baumannii  growth via selective inhibition of  Ab DHFR and is therefore a promising scaffold for further antibiotic development against  A. baumannii .

Diaminoquinazoline MMV675968 from Pathogen Box inhibits Acinetobacter baumannii growth through targeting of dihydrofolate reductase