The cytochrome d oxidase complex regulated by fexA is an Achilles' heel in the in vivo survival of vibrio vulnificus.

Vibrio vulnificus is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, V. vulnificus must adapt to redox fluctuations in vivo. In the present study, we show that deletion of V. vulnificus fexA gene caused hypersensitivity to acid and reactive oxygen species. The ΔfexA mutant exhibited severe in vivo survival defects. For deeper understanding the role of fexA gene on the successful V. vulnificus infection, we analyzed differentially expressed genes in ΔfexA mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the ΔfexA mutant under all three culture conditions. Among them, cydAB appeared to dominantly contribute to the defective phenotypes of the ΔfexA mutant. The fexA deletion induced compensatory point mutations in the cydAB promoter region over subcultures, suggesting essentiality. Those point mutations (PcydSMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the ΔfexA mutant. These results indicate that the cydAB operon, being regulated by FexA, plays a crucial role in V. vulnificus survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against V. vulnificus infection.

Efficacy of Dalbavancin and Telavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections.

OBJECTIVES: Two glycopeptide analogues, such as dalbavancin and telavancin, with improved pharmacokinetic/pharmacodynamic parameters have been developed. These two glycopeptide analogues are approved by Food and Drug Administration (FDA) for treatment of various Gram-positive bacterial skin infections. MATERIALS AND METHODS: We have conducted an open labelled prospective randomized study to compare the efficacy of these two drugs. A total of 200 patients diagnosed with acute bacterial skin and skin structure infections (ABSSSI) were recruited for the study. They were randomized to receive either a single dose of dalbavancin 1500 mg i.v (Group I) or telavancin 10 mg/kg intravenously (i.v.) every 24 hours for six days (Group II). The skin infection rating score (SIRS) was calculated on Day 0 for all patients at the time of diagnosis. Signs and symptoms of the lesions were assessed based on the following factors: blistering, exudate/pus, erythema/inflammation and itching/pain. Each factor was classified as one of the following: absent - 0, minimal - 1, moderate - 2 and severe - 3. RESULTS: Clinically successful treatment was defined as complete resolution of clinically meaningful signs and symptoms of infection, including SIRS score of 0. The outcome measure was the percentage of patients with SIRS score of 0 on day 7 (clinical success). The third most common diagnosis at baseline was impetigo (13% in both groups). Patients who received dalbavancin had a higher clinical success rate than those receiving telavancin. CONCLUSION: Findings of the present study show that single i.v dose of dalbavancin is better than telavancin repeated doses in treatment of ABSSSI.