Genome-guided purification of high amounts of the siderophore ornibactin and detection of potentially novel burkholdine derivatives produced by Burkholderia catarinensis 89T.

AIM: The increased availability of genome sequences has enabled the development of valuable tools for the prediction and identification of bacterial natural products. Burkholderia catarinensis 89T produces siderophores and an unknown potent antifungal metabolite. The aim of this work was to identify and purify natural products of B. catarinensis 89T through a genome-guided approach. MATERIALS AND METHODS: The analysis of B. catarinensis 89T genome revealed 16 clusters putatively related to secondary metabolism and antibiotics production. Of particular note was the identification of a nonribosomal peptide synthetase (NRPS) cluster related to the production of the siderophore ornibactin, a hybrid NRPS-polyketide synthase Type 1 cluster for the production of the antifungal glycolipopeptide burkholdine, and a gene cluster encoding homoserine lactones (HSL), probably involved in the regulation of both metabolites. We were able to purify high amounts of the ornibactin derivatives D/C6 and F/C8, while also detecting the derivative B/C4 in mass spectrometry investigations. A group of metabolites with molecular masses ranging from 1188 to 1272 Da could be detected in MS experiments, which we postulate to be new burkholdine analogs produced by B. catarinensis. The comparison of B. catarinensis BGCs with other Bcc members corroborates the hypothesis that this bacterium could produce new derivatives of these metabolites. Moreover, the quorum sensing metabolites C6-HSL, C8-HSL, and 3OH-C8-HSL were observed in LC-MS/MS analysis. CONCLUSION: The new species B. catarinensis is a potential source of new bioactive secondary metabolites. Our results highlight the importance of genome-guided purification and identification of metabolites of biotechnological importance.

New Vein Compression Entities in Patients with Unexplained Leg Swelling.

BACKGROUND: This retrospective study identifies often overlooked anatomical sites for nonthrombotic venous outflow obstruction (NTVO) in patients with unexplained lower extremity edema and pain. METHODS: We reviewed the charts of 75 consecutive patients experiencing symptoms of unexplained lower extremity edema with pain that were unexplained by ultrasound, computed tomography angiography (CTA), and magnetic resonance imaging (MRI), who subsequently underwent venography in an outpatient medical office from 2010 to 2014. We categorized venograms based on the presence or absence of NTVO lesions and calculated prevalence of each at specific sites. The patients with NTVO lesions showing >50% stenosis on venography were then treated with angioplasty and/or stenting. After intervention, we documented subjective levels of pain and edema. RESULTS: Of the 75 venograms reviewed, physicians classified 52 as normal and 23 as showing evidence of compression, including 9 with May-Thurner syndrome and 14 with anatomical compressions at previously underreported sites. These 14 compression sites occurred at the following: iliofemoral vein at the inguinal ligament region (n = 7, 50%), external iliac vein at the iliac artery bifurcation (n = 1, 7.1%), both inguinal ligament region and iliac artery bifurcation (n = 4, 28.6%), and popliteal vein at the popliteal fossa (n = 2, 14.3%). Nine of the 14 patients (64.3%) reported total or near total resolution of lower extremity pain and edema at follow-up between 1 and 7 months (mean = 5.3 ± 2 months, median = 6 months) after balloon angioplasty and/or stent. Five with failed primary interventions underwent subsequent stenting and/or angioplasty and reported total or near total resolution of pain and clinical resolution of edema. CONCLUSIONS: This study provides evidence to broaden the disease profile of venous compression syndromes to other sites such as the hypogastric artery, inguinal ligament, and popliteal fossa. The results support previous research that suggests increased incidence of NTVO exists among patients with unexplained lower extremity edema and pain. In an effort to encourage further exploration, we developed a diagnostic algorithm to support a critical and systematic review of patients with lower extremity edema and pain that may go unexplained using traditional diagnostic measures, including ultrasound, CTA, and MRI alone.