Synthetic compounds are a vital source of antimicrobial agents. To uncover therapeutically effective antimicrobial agents from a chemical library, we screened over 100,000 synthetic compounds for in vitro antimicrobial activity against methicillin-resistant Staphylococcus aureus and evaluated the in vivo therapeutic effectiveness of the hits in S. aureus-infected silkworms. Three antimicrobial agents exhibited therapeutic effects in the silkworm infection model. One of these, GPI0363, a novel spiro-heterocyclic compound, was bacteriostatic and inhibited RNA synthesis in S. aureus cells. GPI0363-resistant S. aureus strains harbored a point mutation in the gene encoding the primary sigma factor, SigA, of RNA polymerase, and this mutation was responsible for the resistance to GPI0363. We further revealed that GPI0363 could bind to SigA, inhibit promoter-specific transcription in vitro, and prolong the survival of mice infected with methicillin-resistant S. aureus. Thus, GPI0363 is an attractive candidate therapeutic agent against drug-resistant S. aureus infections.
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 May 2024.
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#5,768,968
of 22,963,381 outputs
Outputs from Frontiers in Microbiology
#5,447
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Outputs of similar age
#90,741
of 309,706 outputs
Outputs of similar age from Frontiers in Microbiology
#186
of 516 outputs
Altmetric has tracked 22,963,381 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 25,008 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 309,706 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 516 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
