A new regulator of pathogenicity (bvlR) is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa.
LysR-type transcriptional regulators (LTTRs) are the most common family of transcriptional regulators found in the opportunistic pathogen Pseudomonas aeruginosa. 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 P. aeruginosa pathogenicity within the Caenorhabditis elegans 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 cupA and alg genes. This highlights the importance of BvlR as a new virulence regulator in P. aeruginosa with a central role in modulating key events in the pathogen-host interactome.
BIOMERIT Research Centre, School of Microbiology, University College Cork, Cork, Ireland.
Ronan R
RR
McCarthy
BIOMERIT Research Centre, School of Microbiology, University College Cork, Cork, Ireland.
Marlies J
MJ
Mooij
BIOMERIT Research Centre, School of Microbiology, University College Cork, Cork, Ireland.
F Jerry
FJ
Reen
Laboratory of Microbiology Signals and Microenvironment LMSM EA4312, University of Rouen, 55 rue Saint Germain, 27000 Evreux, France.
Olivier
O
Lesouhaitier
Curtin University, School of Biomedical Sciences, Perth, WA, Australia.|BIOMERIT Research Centre, School of Microbiology, University College Cork, Cork, Ireland.
Fergal
F
O'Gara
D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development; D017173:Caenorhabditis elegans / Q000382:microbiology; D005098:Exotoxins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D006801:Humans; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; D005098:Exotoxins; D012097:Repressor Proteins; D014157:Transcription Factors; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C073470:LysR protein, Bacteria