TY - JOUR
T1 - The Transcription Factor ArcA Modulates Salmonella’s Metabolism in Response to Neutrophil Hypochlorous Acid-Mediated Stress
AU - Pardo-Esté, Coral
AU - Castro-Severyn, Juan
AU - Krüger, Gabriel I.
AU - Cabezas, Carolina Elizabeth
AU - Briones, Alan Cristóbal
AU - Aguirre, Camila
AU - Morales, Naiyulin
AU - Baquedano, Maria Soledad
AU - Sulbaran, Yoelvis Noe
AU - Hidalgo, Alejandro A.
AU - Meneses, Claudio
AU - Poblete-Castro, Ignacio
AU - Castro-Nallar, Eduardo
AU - Valvano, Miguel A.
AU - Saavedra, Claudia P.
N1 - Publisher Copyright:
© Copyright © 2019 Pardo-Esté, Castro-Severyn, Krüger, Cabezas, Briones, Aguirre, Morales, Baquedano, Sulbaran, Hidalgo, Meneses, Poblete-Castro, Castro-Nallar, Valvano and Saavedra.
PY - 2019/12/5
Y1 - 2019/12/5
N2 - Salmonella Typhimurium, a bacterial pathogen with high metabolic plasticity, can adapt to different environmental conditions; these traits enhance its virulence by enabling bacterial survival. Neutrophils play important roles in the innate immune response, including the production of microbicidal reactive oxygen species (ROS). In addition, the myeloperoxidase in neutrophils catalyzes the formation of hypochlorous acid (HOCl), a highly toxic molecule that reacts with essential biomolecules, causing oxidative damage including lipid peroxidation and protein carbonylation. The bacterial response regulator ArcA regulates adaptive responses to oxygen levels and influences the survival of Salmonella inside phagocytic cells. Here, we demonstrate by whole transcriptomic analyses that ArcA regulates genes related to various metabolic pathways, enabling bacterial survival during HOCl-stress in vitro. Also, inside neutrophils, ArcA controls the transcription of several metabolic pathways by downregulating the expression of genes related to fatty acid degradation, lysine degradation, and arginine, proline, pyruvate, and propanoate metabolism. ArcA also upregulates genes encoding components of the oxidative pathway. These results underscore the importance of ArcA in ATP generation inside the neutrophil phagosome and its participation in bacterial metabolic adaptations during HOCl stress.
AB - Salmonella Typhimurium, a bacterial pathogen with high metabolic plasticity, can adapt to different environmental conditions; these traits enhance its virulence by enabling bacterial survival. Neutrophils play important roles in the innate immune response, including the production of microbicidal reactive oxygen species (ROS). In addition, the myeloperoxidase in neutrophils catalyzes the formation of hypochlorous acid (HOCl), a highly toxic molecule that reacts with essential biomolecules, causing oxidative damage including lipid peroxidation and protein carbonylation. The bacterial response regulator ArcA regulates adaptive responses to oxygen levels and influences the survival of Salmonella inside phagocytic cells. Here, we demonstrate by whole transcriptomic analyses that ArcA regulates genes related to various metabolic pathways, enabling bacterial survival during HOCl-stress in vitro. Also, inside neutrophils, ArcA controls the transcription of several metabolic pathways by downregulating the expression of genes related to fatty acid degradation, lysine degradation, and arginine, proline, pyruvate, and propanoate metabolism. ArcA also upregulates genes encoding components of the oxidative pathway. These results underscore the importance of ArcA in ATP generation inside the neutrophil phagosome and its participation in bacterial metabolic adaptations during HOCl stress.
KW - ArcA
KW - hypochlorous acid
KW - neutrophils
KW - Salmonella
KW - transcription factor
UR - http://www.scopus.com/inward/record.url?scp=85076964553&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2019.02754
DO - 10.3389/fmicb.2019.02754
M3 - Article
AN - SCOPUS:85076964553
SN - 1664-302X
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 2754
ER -