Brucella Genetic Variability in Wildlife Marine Mammals Populations Relates to Host Preference and Ocean Distribution

Intracellular bacterial pathogens probably arose when their ancestor adapted from a free-living environment to an intracellular one, leading to clonal bacteria with smaller genomes and less sources of genetic plasticity. Still, this plasticity is needed to respond to the challenges posed by the host. Members of the Brucella genus are facultative-extracellular intracellular bacteria responsible for causing brucellosis in a variety of mammals. The various species keep different host preferences, virulence, and zoonotic potential despite having 97–99% similarity at genome level. Here, we describe elements of genetic variation in Brucella ceti isolated from wildlife dolphins inhabiting the Pacific Ocean and the Mediterranean Sea. Comparison with isolates obtained from marine mammals from the Atlantic Ocean and the broader Brucella genus showed distinctive traits according to oceanic distribution and preferred host. Marine mammal isolates display genetic variability, represented by an important number of IS711 elements as well as specific IS711 and SNPs genomic distribution clustering patterns. Extensive pseudogenization was found among isolates from marine mammals as compared with terrestrial ones, causing degradation in pathways related to energy, transport of metabolites, and regulation/ transcription. Brucella ceti isolates infecting particularly dolphin hosts, showed further degradation of metabolite transport pathways as well as pathways related to cell wall/membrane/envelope biogenesis and motility. Thus, gene loss through pseudogenization is a source of genetic variation in Brucella, whichinturn, relates to adaptation to different hosts.This is relevant to understand the natural history of bacterial diseases, their zoonotic potential, and the impact of human interventions such as domestication.Comisión Nacional para la Gestión de la Biodiversidad/[R-028-203-OT]/CONAGEBIO/Costa RicaMinisterio de Ciencia, Tecnología y Telecomunicaciones/[FV-004-13]/MICITT/Costa RicaWellcome Trust/[098051]/WT/LondresWellcome Trust/[106690/Z/14/Z]/WT/LondresUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

The caveolae-associated coiled-coil protein, NECC2, regulates insulin signalling in Adipocytes

Adipocyte dysfunction in obesity is commonly associated with impaired insulin sig-nalling in adipocytes and insulin resistance. Insulin signalling has been associatedwith caveolae, which are coated by large complexes of caveolin and cavin proteins,along with proteins with membrane‐binding and remodelling properties. Here, weanalysed the regulation and function of a component of caveolae involved in growthfactor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2(NECC2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC2 expressionincreased during adipogenesis. Furthermore, NECC2 co‐immunoprecipitated withcaveolin‐1 (CAV1) and exhibited a distribution pattern similar to that of the compo-nents of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin.Interestingly, NECC2 overexpression enhanced insulin‐activated Akt phosphoryla-tion, whereas NECC2 downregulation impaired insulin‐induced phosphorylation ofAkt and ERK2. Finally, an up‐regulation ofNECC2in subcutaneous and omental adi-pose tissue was found in association with human obesity and insulin resistance. Thiseffect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperin-sulinemia. Overall, the present study identifies NECC2 as a component of adipocytecaveolae that is regulated in response to obesity and associated metabolic complica-tions, and supports the contribution of this protein as a molecular scaffold modulat-ing insulin signal transduction at these membrane microdomains

The caveolae-associated coiled-coil protein, NECC2, regulates insulin signalling in Adipocytes

Adipocyte dysfunction in obesity is commonly associated with impaired insulin sig-nalling in adipocytes and insulin resistance. Insulin signalling has been associatedwith caveolae, which are coated by large complexes of caveolin and cavin proteins,along with proteins with membrane‐binding and remodelling properties. Here, weanalysed the regulation and function of a component of caveolae involved in growthfactor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2(NECC2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC2 expressionincreased during adipogenesis. Furthermore, NECC2 co‐immunoprecipitated withcaveolin‐1 (CAV1) and exhibited a distribution pattern similar to that of the compo-nents of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin.Interestingly, NECC2 overexpression enhanced insulin‐activated Akt phosphoryla-tion, whereas NECC2 downregulation impaired insulin‐induced phosphorylation ofAkt and ERK2. Finally, an up‐regulation ofNECC2in subcutaneous and omental adi-pose tissue was found in association with human obesity and insulin resistance. Thiseffect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperin-sulinemia. Overall, the present study identifies NECC2 as a component of adipocytecaveolae that is regulated in response to obesity and associated metabolic complica-tions, and supports the contribution of this protein as a molecular scaffold modulat-ing insulin signal transduction at these membrane microdomains

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN