Examinando por Autor "Hidalgo, A.A."

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    SmvA, and not AcrB, is the major efflux pump for acriflavine and related compounds in Salmonella enterica serovar Typhimurium
    (Oxford University Press, 2008-12) Villagra, N.A.; Hidalgo, A.A.; Santiviago, C.A.; Saavedra, C.P.; Mora, G.C.
    Objectives: The aim was to study the role played by SmvA pump in the efflux of quaternary ammonium compounds (QACs) in Salmonella enterica serovar Typhimurium (Salmonella Typhimurium). Methods: Mutants in the smvA, acrB and tolC genes were constructed by the red swap method. P22 was used to transduce tolC to acrB and smvA mutant strains. The susceptibility of these strains to acriflavine and a variety of QACs was determined by MIC assays. Results: In comparison with the Salmonella Typhimurium wild-type strain, the smvA mutant was more susceptible to QACs than the acrB mutant strain. A tolC single mutant was more susceptible than an acrB mutant to QACs, acriflavine, ethidium bromide, malachite green and pyronin B. The tolC - acrB double mutant was as susceptible as the single tolC mutant to QACs. Additionally, the smvA mutant strain was more susceptible to acriflavine than the acrB mutant (MICs = 31.3 versus 125 mg/L, i.e. 4-fold). Finally, the tolC - smvA double mutant (3.9 mg/L) was approximately 10 times more susceptible to acriflavine than either smvA (31.3 mg/L) or tolC (31.3 mg/L) single mutants. Conclusions: It is the SmvA efflux pump, and not AcrB, that plays the major role in the efflux of acriflavine and other QACs from Salmonella Typhimurium. This apparently conflicting report is due to the fact that in Escherichia coli the smvA gene does not exist. Our results suggest that tolC and smvA genes encode components of two different efflux systems with overlapping specificities that work in parallel to export acriflavine and other QACs. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
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    The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimurium
    (Public Library of Science, 2018-09) Pardo-Esté, C.; Hidalgo, A.A.; Aguirre, C.; Inostroza, A.; Briones, A.C.; Cabezas, C.E.; Castro-Severyn, J.; Fuentes, J.A.; Opazo, C.M.; Riedel, C.A.; Otero, C.; Pacheco, R.; Valvano, M.A.; Saavedra, C.P.
    Salmonella enterica Serovar Typhimurium (S. Typhimurium) is an intracellular bacterium that overcomes host immune system barriers for successful infection. The bacterium colonizes the proximal small intestine, penetrates the epithelial layer, and is engulfed by macrophages and neutrophils. Intracellularly, S. Typhimurium encounters highly toxic reactive oxygen species including hydrogen peroxide and hypochlorous acid. The molecular mechanisms of Salmonella resistance to intracellular oxidative stress is not completely understood. The ArcAB two-component system is a global regulatory system that responds to oxygen. In this work, we show that the ArcA response regulator participates in Salmonella adaptation to changing oxygen levels and is also involved in promoting intracellular survival in macrophages and neutrophils, enabling S. Typhimurium to successfully establish a systemic infection. © 2018 Pardo-Esté et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    Xylose Improves Antibiotic Activity of Chloramphenicol and Tetracycline against K. pneumoniae and A. baumannii in a Murine Model of Skin Infection
    (Hindawi Limited, 2018) Hidalgo, A.A.; Arias, Á.J.; Fuentes, J.A.; García, P.; Mora, G.C.; Villagra, N.A.
    Increased resistance to antimicrobials in clinically important bacteria has been widely reported. The major mechanism causing multidrug resistance (MDR) is mediated by efflux pumps, proteins located in the cytoplasmic membrane to exclude antimicrobial drug. Some efflux pumps recognize and expel a variety of unrelated antimicrobial agents, while other efflux pumps can expel only one specific class of antibiotics. Previously, we have reported that xylose decreases the efflux-mediated antimicrobial resistance in Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii in vitro. In this work, we assessed the effectiveness of combining xylose with antibiotics to kill resistant Acinetobacter baumannii and Klebsiella pneumoniae in a murine model of skin infection. Skin infections were established by seeding 10 9 bacteria onto eroded skin of mice. Mice treated with the antibiotic alone or with a mixture of glucose and antibiotics or xylose and antibiotics were compared to a control group that was infected but received no further treatment. We observed that the mixtures xylose-tetracycline and xylose-chloramphenicol produced a decrease of at least 10 times viable Acinetobacter baumannii and Klebsiella pneumoniae recovered from infected skin, compared with mice treated with the antibiotic alone. Our results show that xylose improves the antibiotic activity of tetracycline and chloramphenicol against efflux-mediated resistance Acinetobacter baumannii and Klebsiella pneumoniae, in a murine model of skin infection. We envision these combined formulations as an efficient treatment of skin infections with bacteria presenting efflux-mediated resistance, in both humans and animals. © 2018 Alejandro A. Hidalgo et al.