1887

Abstract

LysR-type transcriptional regulators (LTTRs) are the most common family of transcriptional regulators found in the opportunistic pathogen . They are known to regulate a wide variety of virulence determinants and have emerged recently as positive global regulators of pathogenicity in a broad spectrum of important bacterial pathogens. However, in spite of their key role in modulating expression of key virulence determinants underpinning pathogenic traits associated with the process of infection, surprisingly few are found to be transcriptionally altered by contact with host cells. BvlR (PA14_26880) an LTTR of previously unknown function, has been shown to be induced in response to host cell contact, and was therefore investigated for its potential role in virulence. BvlR expression was found to play a pivotal role in the regulation of acute virulence determinants such as type III secretion system and exotoxin A production. BvlR also played a key role in pathogenicity within the acute model of infection. Loss of BvlR led to an inability to form tight microcolonies, a key step in biofilm formation in the cystic fibrosis lung, although surface attachment was increased. Unusually for LTTRs, BvlR was shown to exert its influence through the transcriptional repression of many genes, including the virulence-associated and genes. This highlights the importance of BvlR as a new virulence regulator in with a central role in modulating key events in the pathogen–host interactome.

Funding
This study was supported by the:
  • Science Foundation of Ireland (Award SSPC212/RC/2275, 09/RFP/BMT 2350, 12/TIDA/B2405, 12/TIDA/B2411 and 07/IN.1/B948)
  • Department of Agriculture, Fisheries and Food (Award DAFF11/F/009MabS and FIRM/RSF/CoFoRD)
  • Environmental Protection Agency (Award EPA 2008-PhD/S-2)
  • Irish Research Council for Science, Engineering and Technology (Award RS/2010/2413 and PD/2011/2414)
  • European Commission (Award Marie Curie 256596, FP7-KBBE-2012-6, 607786 and FP7-PEOPLE-2013-ITN)
  • Marine Microbial Biodiversity, Bioinformatics and Biotechnology (Award OCEAN 2012 287589)
  • Marine Micro-organisms: Cultivation Methods for improving their Biotechnological Applications (Award CP-TP 311975)
  • Increasing Value and Flow in the Marine Biodiscovery Pipeline (Award C2CRA 2007/082, Marine Institute and CP-TP 312184)
  • Teagasc (Award Walsh Fellowship 2013)
  • Health Research Board (Award HRA/2009/146)
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2014-07-01
2024-04-18
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