Replication of Crohn’s Disease Mucosal E. coli Isolates inside Macrophages Correlates with Resistance to Superoxide and Is Dependent on Macrophage NF-kappa B Activation
Identifieur interne : 000471 ( Main/Exploration ); précédent : 000470; suivant : 000472Replication of Crohn’s Disease Mucosal E. coli Isolates inside Macrophages Correlates with Resistance to Superoxide and Is Dependent on Macrophage NF-kappa B Activation
Auteurs : Ahmed Tawfik [Irlande (pays)] ; Paul Knight [Royaume-Uni] ; Carrie A. Duckworth ; D. Mark Pritchard ; Jonathan M. Rhodes ; Barry J. CampbellSource :
- Pathogens [ 2076-0817 ] ; 2019.
Abstract
Mucosa-associated
Url:
DOI: 10.3390/pathogens8020074
PubMed: 31181736
PubMed Central: 6630736
Affiliations:
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Le document en format XML
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Isolates inside Macrophages Correlates with Resistance to Superoxide and Is Dependent on Macrophage NF-kappa B Activation</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Replication of Crohn’s Disease Mucosal <italic>E. coli</italic>
Isolates inside Macrophages Correlates with Resistance to Superoxide and Is Dependent on Macrophage NF-kappa B Activation</title>
<author><name sortKey="Tawfik, Ahmed" sort="Tawfik, Ahmed" uniqKey="Tawfik A" first="Ahmed" last="Tawfik">Ahmed Tawfik</name>
<affiliation><nlm:aff id="af1-pathogens-08-00074">Gastroenterology Research Unit, Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK;<email>ahmedtawfik13@yahoo.com</email>
(A.T.);<email>paul.knight@mft.nhs.uk</email>
(P.K.);<email>carried@liv.ac.uk</email>
(C.A.D.);<email>dmpritch@liv.ac.uk</email>
(D.M.P.);<email>rhodesjm@liv.ac.uk</email>
(J.M.R.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af2-pathogens-08-00074">Gastroenterology Department, Beaumont Hospital, Dublin 9, Ireland</nlm:aff>
<country xml:lang="fr">Irlande (pays)</country>
<wicri:regionArea>Gastroenterology Department, Beaumont Hospital, Dublin 9</wicri:regionArea>
<wicri:noRegion>Dublin 9</wicri:noRegion>
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<author><name sortKey="Knight, Paul" sort="Knight, Paul" uniqKey="Knight P" first="Paul" last="Knight">Paul Knight</name>
<affiliation><nlm:aff id="af1-pathogens-08-00074">Gastroenterology Research Unit, Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK;<email>ahmedtawfik13@yahoo.com</email>
(A.T.);<email>paul.knight@mft.nhs.uk</email>
(P.K.);<email>carried@liv.ac.uk</email>
(C.A.D.);<email>dmpritch@liv.ac.uk</email>
(D.M.P.);<email>rhodesjm@liv.ac.uk</email>
(J.M.R.)</nlm:aff>
</affiliation>
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<wicri:regionArea>Gastroenterology Department, University Hospital of South Manchester, Wythenshawe M23 9LT</wicri:regionArea>
<wicri:noRegion>Wythenshawe M23 9LT</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Duckworth, Carrie A" sort="Duckworth, Carrie A" uniqKey="Duckworth C" first="Carrie A." last="Duckworth">Carrie A. Duckworth</name>
<affiliation><nlm:aff id="af1-pathogens-08-00074">Gastroenterology Research Unit, Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK;<email>ahmedtawfik13@yahoo.com</email>
(A.T.);<email>paul.knight@mft.nhs.uk</email>
(P.K.);<email>carried@liv.ac.uk</email>
(C.A.D.);<email>dmpritch@liv.ac.uk</email>
(D.M.P.);<email>rhodesjm@liv.ac.uk</email>
(J.M.R.)</nlm:aff>
</affiliation>
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<author><name sortKey="Pritchard, D Mark" sort="Pritchard, D Mark" uniqKey="Pritchard D" first="D. Mark" last="Pritchard">D. Mark Pritchard</name>
<affiliation><nlm:aff id="af1-pathogens-08-00074">Gastroenterology Research Unit, Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK;<email>ahmedtawfik13@yahoo.com</email>
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(C.A.D.);<email>dmpritch@liv.ac.uk</email>
(D.M.P.);<email>rhodesjm@liv.ac.uk</email>
(J.M.R.)</nlm:aff>
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<author><name sortKey="Rhodes, Jonathan M" sort="Rhodes, Jonathan M" uniqKey="Rhodes J" first="Jonathan M." last="Rhodes">Jonathan M. Rhodes</name>
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(P.K.);<email>carried@liv.ac.uk</email>
(C.A.D.);<email>dmpritch@liv.ac.uk</email>
(D.M.P.);<email>rhodesjm@liv.ac.uk</email>
(J.M.R.)</nlm:aff>
</affiliation>
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<author><name sortKey="Campbell, Barry J" sort="Campbell, Barry J" uniqKey="Campbell B" first="Barry J." last="Campbell">Barry J. Campbell</name>
<affiliation><nlm:aff id="af1-pathogens-08-00074">Gastroenterology Research Unit, Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK;<email>ahmedtawfik13@yahoo.com</email>
(A.T.);<email>paul.knight@mft.nhs.uk</email>
(P.K.);<email>carried@liv.ac.uk</email>
(C.A.D.);<email>dmpritch@liv.ac.uk</email>
(D.M.P.);<email>rhodesjm@liv.ac.uk</email>
(J.M.R.)</nlm:aff>
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<series><title level="j">Pathogens</title>
<idno type="eISSN">2076-0817</idno>
<imprint><date when="2019">2019</date>
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<front><div type="abstract" xml:lang="en"><p>Mucosa-associated <italic>Escherichia coli</italic>
are increased in Crohn’s disease (CD) and colorectal cancer (CRC). CD isolates replicate within macrophages but the specificity of this effect for CD and its mechanism are unclear. Gentamicin exclusion assay was used to assess <italic>E. coli</italic>
replication within J774.A1 murine macrophages. <italic>E. coli</italic>
growth was assessed following acid, low-nutrient, nitrosative, oxidative and superoxide stress, mimicking the phagolysosome. Twelve of 16 CD <italic>E. coli</italic>
isolates replicated >2-fold within J774.A1 macrophages; likewise for isolates from 6/7 urinary tract infection (UTI), 8/9 from healthy subjects, compared with 2/6 ulcerative colitis, 2/7 colorectal cancer and 0/3 laboratory strains. CD mucosal <italic>E. coli</italic>
were tolerant of acidic, low-nutrient, nitrosative and oxidative stress. Replication within macrophages correlated strongly with tolerance to superoxide stress (rho = 0.44, <italic>p</italic>
= 0.0009). Exemplar CD <italic>E. coli</italic>
HM605 and LF82 were unable to survive within <italic>Nfκb1<sup>-/-</sup>
</italic>
murine bone marrow-derived macrophages. In keeping with this, pre-incubation of macrophages with hydrocortisone (0.6 µM for 24 h) caused 70.49 ± 12.11% inhibition of intra-macrophage replication. Thus, CD mucosal <italic>E. coli</italic>
commonly replicate inside macrophages, but so do some UTI and healthy subject strains. Replication correlates with resistance to superoxide and is highly dependent on macrophage NF-κB signalling. This may therefore be a good therapeutic target.</p>
</div>
</front>
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