Highlights d Phage PBC5 encodes a novel endolysin LysPBC5 against Bacillus cereus d LysPBC5 recognizes host cell walls via a conjoined tandem SH3b repeat fold d The SH3b repeat fold interacts with peptidoglycans in a bidentate manner d LysPBC5 primarily binds to glycan strands of the cell-wall structure
As
an alternative strategy to fight antibiotic resistance, two-component
systems (TCSs) have emerged as novel targets. Among TCSs, master virulence
regulators that control the expression of multiple virulence factors
are considered as excellent antivirulence targets. In Staphylococcus
aureus, virulence factor expression is tightly regulated
by a few master regulators, including the SaeRS TCS. In this study,
we used a SaeRS GFP-reporter system to screen natural compound inhibitors
of SaeRS, and identified xanthoangelol B 1, a prenylated
chalcone from Angelica keiskei as a hit. We have
synthesized 1 and its derivative PM-56 and
shown that 1 and PM-56 both had excellent
inhibitory potency against the SaeRS TCS, as demonstrated by various in vitro and in vivo experiments. As a
mode of action, 1 and PM-56 were shown to
bind directly to SaeS and inhibit its histidine kinase activity, which
suggests a possibility of a broad spectrum inhibitor of histidine
kinases.
An Ag-RDT is less likely to be accepted as an initial test method for early diagnosis owing to its low sensitivity. However, our self-collection method, Ag-RDT using BG-based saliva specimens, showed significantly enhanced detection sensitivity and specificity toward SARS-CoV-2 including the Alpha and Delta variants in all patients tested within 6 days of illness.
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