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Perez F.,Case Western Reserve University | Villegas M.V.,Centro Internacional Of Entrenamiento E Investigaciones Medicas
Current Opinion in Infectious Diseases | Year: 2015

Purpose of review It is widely accepted that infection control, advanced diagnostics, and novel therapeutics are crucial to mitigate the impact of antibiotic-resistant bacteria. The role of global, national, and regional surveillance systems as part of the response to the challenge posed by antibiotic resistance is not sufficiently highlighted. We provide an overview of contemporary surveillance programs, with emphasis on gram-negative bacteria. Recent findings The WHO and public health agencies in Europe and the United States recently published comprehensive surveillance reports. These highlight the emergence and dissemination of carbapenem-resistant Enterobacteriaceae and other multidrug-resistant gram-negative bacteria. In Israel, public health action to control carbapenem-resistant Enterobacteriaceae, especially Klebsiella pneumoniae carbapenemase producing K. pneumoniae, has advanced together with a better understanding of its epidemiology. Surveillance models adapted to the requirements and capacities of each country are in development. Summary Robust surveillance systems are essential to combat antibiotic resistance, and need to emphasize a 'one health' approach. Refinements in surveillance will come from advances in bioinformatics and genomics that permit the integration of global and local information about antibiotic consumption in humans and animals, molecular mechanisms of resistance, and bacterial genotyping. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Gomez M.A.,Centro Internacional Of Entrenamiento E Investigaciones Medicas | Olivier M.,McGill University
Virulence | Year: 2010

The outcome of Leishmania infection depends both on host and pathogen factors. Macrophages, the specialized host cells for uptake and intracellular development of Leishmania, play a central role in the control of infection. Leishmania has evolved strategies to downregulate host cell functions, largely mediated by the parasite-induced activation of macrophage protein tyrosine phosphatases (PTPs). We have recently identified PTP1B and TCPTP as two additional PTPs engaged upon Leishmania infection and have unraveled an intimate interaction between the Leishmania surface protease GP63 and host PTPs, which mediates a mechanism of cleavage-dependent PTP activation. Here we discuss new perspectives for GP63-mediated parasite virulence and propose putative mechanisms of GP63 internalization into host macrophages and access to intracellular substrates. © 2010 Landes Bioscience.

Jaramillo Ramirez G.I.,Rothamsted Research | Jaramillo Ramirez G.I.,Centro Internacional Of Entrenamiento E Investigaciones Medicas | Logan J.G.,London School of Hygiene and Tropical Medicine | Loza-Reyes E.,Rothamsted Research | And 2 more authors.
PLoS ONE | Year: 2012

The primary defence against mosquitoes and other disease vectors is often the application of a repellent. Despite their common use, the mechanism(s) underlying the activity of repellents is not fully understood, with even the mode of action of DEET having been reported to be via different mechanisms; e.g. interference with olfactory receptor neurones or actively detected by olfactory receptor neurones on the antennae or maxillary palps. In this study, we discuss a novel mechanism for repellence, one of P450 inhibition. Thirteen essential oil extracts from Colombian plants were assayed for potency as P450 inhibitors, using a kinetic fluorometric assay, and for repellency using a modified World Health Organisation Pesticide Evaluations Scheme (WHOPES) arm-in cage assay with Stegomyia (Aedes) aegypti mosquitoes. Bootstrap analysis on the inhibition analysis revealed a significant correlation between P450-inhibition and repellent activity of the oils. © 2012 Jaramillo Ramirez et al.

Jaramillo M.,McGill University | Gomez M.A.,McGill University | Gomez M.A.,Centro Internacional Of Entrenamiento E Investigaciones Medicas | Larsson O.,McGill University | And 13 more authors.
Cell Host and Microbe | Year: 2011

The protozoan parasite Leishmania alters the activity of its host cell, the macrophage. However, little is known about the effect of Leishmania infection on host protein synthesis. Here, we show that the Leishmania protease GP63 cleaves the mammalian/mechanistic target of rapamycin (mTOR), a serine/threonine kinase that regulates the translational repressor 4E-BP1. mTOR cleavage results in the inhibition of mTOR complex 1 (mTORC1) and concomitant activation of 4E-BP1 to promote Leishmania proliferation. Consistent with these results, pharmacological activation of 4E-BPs with rapamycin, results in a dramatic increase in parasite replication. In contrast, genetic deletion of 4E-BP1/2 reduces parasite load in macrophages ex vivo and decreases susceptibility to cutaneous leishmaniasis in vivo. The parasite resistant phenotype of 4E-BP1/2 double-knockout mice involves an enhanced type I IFN response. This study demonstrates that Leishmania evolved a survival mechanism by activating 4E-BPs, which serve as major targets for host translational control. © 2011 Elsevier Inc.

Santaella J.,Centro Internacional Of Entrenamiento E Investigaciones Medicas | Ocampo C.B.,Centro Internacional Of Entrenamiento E Investigaciones Medicas | Saravia N.G.,Centro Internacional Of Entrenamiento E Investigaciones Medicas | Mendez F.,University of Valle | And 4 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2011

Peridomestic transmission of American cutaneous leishmaniasis is increasingly reported and dogs may be a reservoir of Leishmania (Viannia) in this setting. We investigated the prevalence of infection in dogs in Chaparral County, Colombia, the focus of an epidemic of human cutaneous leishmaniasis caused by Leishmania ( Viannia ) guyanensis. Two (0.72%) of 279 dogs had lesions typical of cutaneous leishmaniasis that were biopsy positive by kinetoplast DNA polymerase chain reaction-Southern blotting. Seroprevalence was 2.2% (6 of 279) by enzyme-linked immunosorbent assay. Buffy coat and ear skin biopsy specimens were positive by polymerase chain reaction-Southern blotting in 7.3% (10 of 137) and 11.4% (12 of 105) of dogs, respectively. Overall 20% of dogs (21 of 105) showed positive results for one or more tests. Amplification and sequencing of the Leishmania 7SL RNA gene identified L. guyanensis in one dog and L. braziliensis in two dogs. No association was identified between the risk factors evaluated and canine infection. Dogs may contribute to transmission but their role in this focus appears to be limited. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene.

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