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Bacterial adrenergic sensors regulate virulence of enteric pathogens in the gut

Moreira, CG, Russell, R, Mishra, AA, Narayanan, S, Ritchie, Jennifer M., Waldor, MK, Curtis, MM, Winter, SE, Weinshnker, D and Sperandio, V (2016) Bacterial adrenergic sensors regulate virulence of enteric pathogens in the gut mBio, 7 (3), e00826-16. pp. 1-14.

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Enteric pathogens such as enterohemorrhagic E. coli (EHEC) and Citrobacter rodentium, which is largely used as a surrogate EHEC model for murine infections, are exposed to several host neurotransmitters in the gut. An important chemical exchange within the gut involves the neurotransmitters epinephrine and/or norepinephrine, extensively reported to increase virulence gene expression in EHEC, acting through two bacterial adrenergic sensors: QseC and QseE. However, EHEC is unable to establish itself and cause its hallmark lesions, attaching and effacing (AE) lesions, on murine enterocytes. To address the role of these neurotransmitters during enteric infection, we employed C. rodentium. Both EHEC and C. rodentium harbor the locus of enterocyte effacement (LEE) that is necessary for AE lesion formation. Here we show that expression of the LEE, as well as other virulence genes in C. rodentium is also activated by epinephrine and/or norepinephrine. Both QseC and QseE are required for LEE gene activation in C. rodentium, and the qseC and qseE mutants are attenuated for murine infection. C. rodentium has decreased ability to colonize dopamine β hydroxylase (Dbh-/-) knockout mice, which do not produce epinephrine and norepinephrine. Both adrenergic sensors are required for C. rodentium to sense these neurotransmitters and activate the LEE genes during infection. These data indicate that epinephrine and norepinephrine are sensed by bacterial adrenergic receptors during enteric infection to promote activation of their virulence repertoire. This is the first report of the role of these neurotransmitters during mammalian gastrointestinal (GI) infection by a non-invasive pathogen.

Item Type: Article
Subjects : subj_Medical_Science
Divisions : Faculty of Health and Medical Sciences
Authors :
Moreira, CG
Russell, R
Mishra, AA
Narayanan, S
Ritchie, Jennifer
Waldor, MK
Curtis, MM
Winter, SE
Weinshnker, D
Sperandio, V
Date : 7 June 2016
DOI : 10.1128/mBio.00826-16
Copyright Disclaimer : Copyright © 2016 Moreira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 16 May 2016 14:48
Last Modified : 20 Mar 2019 14:45

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