Carotenoid pigments of Staphylococcus aureus provide integrity to its cell membrane (CM) and limit oxidative host defense mechanisms. However, the role of carotenoids in staphylococcal resistance to nonoxidative host defenses has not been characterized. The current study examined the relationship among CM carotenoid content, membrane order, and in vitro susceptibility to daptomycin or to protot...

The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydro...

We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the x-ray cr...

Eighteen strains of Lactobacillus plantarum from different origins were screened for carotenoid production, as many of them exhibited a deep yellow pigmentation when cultured as isolated colonies on MRS-agar plates. We found that most of them produced significative amounts of the yellow C(30) carotenoid 4,4'-diaponeurosporene in the range 1.8 to 54 mg/kg of dry cell weight. Although some of the...

Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. W...

Staphyloxanthin is a membrane-bound carotenoid of Staphylococcus aureus. Here we studied the interaction of staphyloxanthin with reactive oxygen substances (ROS) and showed by comparative analysis of the wild type (WT) and an isogenic crtM mutant that the WT is more resistant to hydrogen peroxide, superoxide radical, hydroxyl radical, hypochloride, and neutrophil killing.

One of the truisms in the medicinal chemistry of antibiotics is that there can never be enough scaffolds and structures, whether of natural or synthetic origin. No matter how successful a new antibiotic is upon clinical introduction, the inevitable selection for resistant microbes will limit its useful lifetime. Resistance to all major classes of antibiotics has been well chronicled, and one of...

The Community Radiative Transfer Model (CRTM) is a powerful and versatile scalar radiative transfer model for satellite data assimilation remote sensing applications. It implemented as an object-oriented Fortran library, enabling flexible code development optimal runtime performance on clusters. downsides of the interface are steep learning curve students reduced productivity users that typical...

"Head-to-head" terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. Here, we report the structures of Staphylococcus aureus dehydrosqualene synthase (CrtM) complexed with its reaction intermediate, presqualene diphosphate (PSPP), the dehydros...