Summary
Quorum sensing is a process of bacterial communication involving production and detection of secreted molecules called autoinducers. Gram-negative bacteria use acyl-homoserine lactone (AHL) autoinducers, which are detected by one of two receptor types. First, cytoplasmic LuxR-type receptors bind accumulated intracellular AHLs. AHL-LuxR complexes bind DNA and alter gene expression. Second, membrane-bound LuxN-type receptors bind accumulated extracellular AHLs. AHL-LuxN complexes relay information internally by phosphorylation cascades that direct gene-expression changes. Here we show that a small molecule, previously identified as an antagonist of LuxN-type receptors, is also a potent antagonist of the LuxR family, despite differences in receptor structure, localization, AHL specificity, and signaling mechanism. Derivatives were synthesized and optimized for potency, and in each case, we characterized the mode of action of antagonism. The most potent antagonist protects Caenorhabditis elegans from quorum-sensing-mediated killing by Chromobacterium violaceum, validating the notion that targeting quorum sensing has potential for antimicrobial drug development.
To determine the e ects of antithrombotic agents compared with each other, with placebo, or with no treatment, in people with infrainguinal (below the anatomical level of the inguinal ligament) peripheral arterial disease who are undergoing peripheral endovascular treatment.
Antithrombotics a er infra-inguinal peripheral endovascular treatment (Protocol)
May–Thurner syndrome (MTS) is caused by compression of the left iliac vein by the right iliac artery, leading to clinical manifestations of outflow obstruction in the lower limb and deep vein thrombosis. There have been increasing reports of iatrogenic MTS caused by medical implants. The authors report the case of a 60-year-old man who developed MTS after stenting of the right common iliac artery. Due to the debilitating nature of the patient’s symptoms of venous congestion in the left leg, he proceeded with endovascular venoplasty and venous stent insertion with concurrent intra-arterial balloon angioplasty of the existing right common iliac artery stent. Technical success and primary patency of arterial and venous stents were achieved. The patient remained asymptomatic at 6 weeks and 3 months follow-up and arterial and venous stents were found to be patent on duplex ultrasound. Surgical management of MTS may include thrombolysis, thrombectomy, venoplasty and stenting of the left common iliac vein. Care must be taken to preserve existing medical implants during treatment of MTS. The authors demonstrate that concurrent angioplasty of the right common iliac artery during treatment of the vein is an effective method of preventing arterial stent disruption during surgical management of MTS.
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