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Your search keyword '"Prasadarao, Nemani V."' showing total 248 results
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248 results on '"Prasadarao, Nemani V."'

1. Mechanisms of Candida albicans trafficking to the brain.

Author

Liu, Yaoping, Mittal, Rahul, Solis, Norma V, Prasadarao, Nemani V, and Filler, Scott G

Subjects
Brain, Animals, Mice, Inbred BALB C, Humans, Mice, Candida albicans, Carrier Proteins, Fungal Proteins, Membrane Glycoproteins, Protein Transport, Plasmids, Male, Human Umbilical Vein Endothelial Cells, Inbred BALB C, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

During hematogenously disseminated disease, Candida albicans infects most organs, including the brain. We discovered that a C. albicans vps51Δ/Δ mutant had significantly increased tropism for the brain in the mouse model of disseminated disease. To investigate the mechanisms of this enhanced trafficking to the brain, we studied the interactions of wild-type C. albicans and the vps51Δ/Δ mutant with brain microvascular endothelial cells in vitro. These studies revealed that C. albicans invasion of brain endothelial cells is mediated by the fungal invasins, Als3 and Ssa1. Als3 binds to the gp96 heat shock protein, which is expressed on the surface of brain endothelial cells, but not human umbilical vein endothelial cells, whereas Ssa1 binds to a brain endothelial cell receptor other than gp96. The vps51Δ/Δ mutant has increased surface expression of Als3, which is a major cause of the increased capacity of this mutant to both invade brain endothelial cells in vitro and traffic to the brain in mice. Therefore, during disseminated disease, C. albicans traffics to and infects the brain by binding to gp96, a unique receptor that is expressed specifically on the surface of brain endothelial cells.

Published
2011

21. CTX-M [beta]-lactamase production and virulence of Escherichia coli K1

Author

Dubois, Damien, Prasadarao, Nemani V., Mittal, Rahul, Bret, Laurent, Roujou-Gris, Marie, and Bonnet, Richard

Subjects
Beta lactamases -- Production processes, Beta lactamases -- Health aspects, Beta lactamases -- Research, Escherichia coli -- Health aspects, Escherichia coli -- Genetic aspects, Escherichia coli -- Research, Virulence (Microbiology) -- Health aspects, Virulence (Microbiology) -- Research
Abstract

Escherichia coli is the second most common cause of neonatal meningitis. Neonatal meningitis E. coli (NMEC) belong mainly to phylogenetic group B2 and harbor numerous virulence factors (1). Since the [...]

Published
2009
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22. Retraction for Hunter et al., “Lactobacillus bulgaricus Prevents Intestinal Epithelial Cell Injury Caused by Enterobacter sakazakii-Induced Nitric Oxide both In Vitro and in the Newborn Rat Model of Necrotizing Enterocolitis”

Author

Hunter, Catherine J., primary, Williams, Monica, additional, Petrosyan, Mikael, additional, Guner, Yigit, additional, Mittal, Rahul, additional, Mock, Dennis, additional, Upperman, Jeffrey S., additional, Ford, Henri R., additional, and Prasadarao, Nemani V., additional

Published
2018
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25. IQGAP1 mediates the disruption of adherens junctions to promote Escherichia coli K1 invasion of brain endothelial cells

Author

Krishnan, Subramanian, Fernandez, G. Esteban, Sacks, David B., and Prasadarao, Nemani V.

Subjects
ras GTPase-Activating Proteins, Escherichia coli, Endothelial Cells, Humans, Adherens Junctions, Protein Multimerization, Article, Actins, Cells, Cultured, beta Catenin
Abstract

The transcellular entry of Escherichia coli K1 through human brain microvascular endothelial cells (HBMEC) is responsible for tight junction disruption, leading to brain oedema in neonatal meningitis. Previous studies demonstrated that outer membrane protein A (OmpA) of E. coli K1 interacts with its receptor, Ecgp96, to induce PKC-α phosphorylation, adherens junction (AJ) disassembly (by dislodging β-catenin from VE-cadherin), and remodelling of actin in HBMEC. We report here that IQGAP1 mediates β-catenin dissociation from AJs to promote actin polymerization required for E. coli K1 invasion of HBMEC. Overexpression of C-terminal truncated IQGAP1 (IQΔC) that cannot bind β-catenin prevents both AJ disruption and E. coli K1 entry. Of note, phospho-PKC-α interacts with the C-terminal portion of Ecgp96 as well as with VE-cadherin after IQGAP1-mediated AJ disassembly. HBMEC overexpressing either C-terminal truncated Ecgp96 (Ecgp96Δ200) or IQΔC upon infection with E. coli showed no interaction of phospho-PKC-α with Ecgp96. These data indicate that the binding of OmpA to Ecgp96 induces PKC-α phosphorylation and association of phospho-PKC-α with Ecgp96, and then signals IQGAP1 to detach β-catenin from AJs. Subsequently, IQGAP1/β-catenin bound actin translocates to the site of E. coli K1 attachment to promote invasion.

Published
2012

26. Experimental Validation of the Predicted Binding Site of Escherichia coli K1 Outer Membrane Protein A to Human Brain Microvascular Endothelial Cells: Identification of Critical Mutations That Prevent E. coli Meningitis

Author

Pascal, Tod A., Abrol, Ravinder, Mittal, Rahul, Wang, Ying, Prasadarao, Nemani V., and Goddard, William A., III

Abstract

Escherichia coli K1, the most common cause of meningitis in neonates, has been shown to interact with GlcNAc1–4GlcNAc epitopes of Ecgp96 on human brain microvascular endothelial cells (HBMECs) via OmpA (outer membrane protein A). However, the precise domains of extracellular loops of OmpA interacting with the chitobiose epitopes have not been elucidated. We report the loop-barrel model of these OmpA interactions with the carbohydrate moieties of Ecgp96 predicted from molecular modeling. To test this model experimentally, we generated E. coli K1 strains expressing OmpA with mutations of residues predicted to be critical for interaction with the HBMEC and tested E. coli invasion efficiency. For these same mutations, we predicted the interaction free energies (including explicit calculation of the entropy) from molecular dynamics (MD), finding excellent correlation (R^2 = 90%) with experimental invasion efficiency. Particularly important is that mutating specific residues in loops 1, 2, and 4 to alanines resulted in significant inhibition of E. coli K1 invasion in HBMECs, which is consistent with the complete lack of binding found in the MD simulations for these two cases. These studies suggest that inhibition of the interactions of these residues of Loop 1, 2, and 4 with Ecgp96 could provide a therapeutic strategy to prevent neonatal meningitis due to E. coli K1.

Published
2010

32. The effects of cytotoxic necrotizing factor 1 expression in the uptake of Escherichia coli K1 by macrophages and the onset of meningitis in newborn mice.

Author

Chang, Alexander C., Krishnan, Subramanian, and Prasadarao, Nemani V.

Subjects
PROTEIN expression, ESCHERICHIA coli, MACROPHAGES, MENINGITIS, BACTERIAL proteins, LABORATORY mice
Abstract

Macrophages are a permissive niche for E. coli K1 multiplication for which the interaction of the bacterial outer membrane protein A and its cognate receptor CD64 are critical. Using in vitro immunofluorescence and live microscopy with ex vivo macrophage cultures from RFP-Lifeact mice, we show that cytotoxic necrotizing factor 1 (CNF1) secreted by E. coli K1 sequesters cellular actin toward microspike formation, thereby limiting actin availability for OmpA-mediated bacterial invasion. Surprisingly, the observed effects of CNF1 occur despite the absence of 67-kDa laminin receptor in macrophages. Concomitantly, the CNF1 deletion mutant of E. coli K1 (Δcnf1) invades macrophages and the brains of newborn mice in greater numbers compared to wild-type. However, the Δcnf1 strain induces less severe pathology in the brain. These results suggest a novel role for CNF1 in limiting E. coli K1 entry intomacrophages while exacerbating disease severity in the brains of newbornmice. [ABSTRACT FROM AUTHOR]

Published
2016
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33. Escherichia coli K1 Modulates Peroxisome Proliferator-Activated Receptor γ and Glucose Transporter 1 at the Blood-Brain Barrier in Neonatal Meningitis.

Author

Krishnan, Subramanian, Chang, Alexander C., Stoltz, Brian M., and Prasadarao, Nemani V.

Subjects
NEONATAL Escherichia coli infections, NEONATAL infections, MENINGITIS in children, BLOOD-brain barrier, GLUCOSE transporters, GLUCOKINASE, PEDIATRIC neurology, PROTEIN analysis, ANIMAL experimentation, ANIMAL populations, BIOCHEMISTRY, BIOLOGICAL models, CARRIER proteins, CELL lines, CELL receptors, NEONATAL diseases, PHENOMENOLOGY, MEMBRANE proteins, MICE, NERVE tissue proteins, RESEARCH funding, BACTERIAL meningitis
Abstract

Escherichia coli K1 meningitis continues to be a major threat to neonatal health. Previous studies demonstrated that outer membrane protein A (OmpA) of E. coli K1 interacts with endothelial cell glycoprotein 96 (Ecgp96) in the blood-brain barrier to enter the central nervous system. Here we show that the interaction between OmpA and Ecgp96 downregulates peroxisome proliferator-activated receptor γ (PPAR-γ) and glucose transporter 1 (GLUT-1) levels in human brain microvascular endothelial cells, causing disruption of barrier integrity and inhibition of glucose uptake. The suppression of PPAR-γ and GLUT-1 by the bacteria in the brain microvessels of newborn mice causes extensive pathophysiology owing to interleukin 6 production. Pretreatment with partial or selective PPAR-γ agonists ameliorate the pathological outcomes of infection by suppressing interleukin 6 production in the brain. Thus, inhibition of PPAR-γ and GLUT-1 by E. coli K1 is a novel pathogenic mechanism in meningitis, and pharmacological upregulation of PPAR-γ and GLUT-1 levels may provide novel therapeutic avenues. [ABSTRACT FROM AUTHOR]

Published
2016
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