FNR regulates expression of important virulence factors contributing to pathogenicity of uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is responsible for the majority of urinary tract infections (UTIs), which are some of the world's most common bacterial infections of humans. Here, we examined the role of FNR (fumarate and nitrate reduction), a well-known global regulator, in the pathogenesis of UPEC infections. We constructed an fnr deletion mutant of UPEC CFT073 and compared it to the wild type for changes in virulence, adherence, invasion, and expression of key virulence factors. Compared to the wild type, the fnr mutant was highly attenuated in the mouse model of human UTI and showed severe defects in adherence to and invasion of bladder and kidney epithelial cells. Our results showed that FNR regulates motility and multiple virulence factors, including expression of type I and P fimbriae, modulation of hemolysin expression, and expression of a novel pathogenicity island involved in α-ketoglutarate metabolism under anaerobic conditions. Our results demonstrate that FNR is a key global regulator of UPEC virulence and controls expression of important virulence factors that contribute to UPEC pathogenicity.

Serum 25-hydroxyvitamin D concentration in patients with psoriasis and rheumatoid arthritis and its association with disease activity and serum tumor necrosis factor-alpha.

OBJECTIVE: To assess vitamin D status in psoriasis and rheumatoid arthritis (RA) patients and to study whether it was associated with disease activity, inflammatory markers, and serum tumor necrosis factor-alpha (TNF-α). METHODS: This cross-sectional study was conducted at Riyadh National Hospital, Riyadh, Saudi Arabia between March and September 2012. It included 43 patients with plaque psoriasis, 55 RA patients and 40 healthy controls matched for age. Blood samples were drawn from all participants for assessment of 25-hydroxyvitamin D [25(OH)D], TNF-α, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), parathyroid hormone (PTH), and serum corrected calcium. Disease activity of psoriasis and RA were assessed using Psoriasis Area and Severity Index (PASI) and Disease Activity Score Index of a 28 joint count (DAS28). RESULTS: We found a significant difference between psoriatic patients, RA patients, and healthy controls in the mean 25(OH)D (11.74±3.60, 15.45±6.42, and 24.55±11.21 ng/ml; p=0.000). We found that 25(OH)D was not correlated with PASI, DAS28, TNF-α, CRP, or ESR in psoriatic and RA patients. CONCLUSION: Serum 25-(OH)D levels are significantly lower in psoriatic and RA patients than in healthy control subjects. Low 25-OHD levels also may provide the rationale for vitamin D supplementation in the treatment of psoriasis and RA. More definitive evidence is also required to demonstrate the clinical benefit of vitamin D supplementation in the treatment of psoriasis and RA.