title: Deletion of the anaerobic regulator HlyX causes reduced colonization and persistence of Actinobacillus pleuropneumoniae in the porcine respiratory tract.
abstract: Actinobacillus pleuropneumoniae, the etiological agent of porcine pleuropneumonia, is able to persist on respiratory epithelia, in tonsils, and in the anaerobic environment of encapsulated lung sequesters. We have demonstrated previously that putative HlyX-regulated genes, coding for dimethyl sulfoxide (DMSO) reductase and aspartate ammonia lyase, are upregulated during infection and that deletions in these genes result in attenuation of the organism. The study presented here investigates the role of HlyX, the fumarate nitrate reductase regulator (FNR) homologue of A. pleuropneumoniae. By constructing an isogenic A. pleuropneumoniae hlyX mutant, the HlyX protein is shown to be responsible for upregulated expression of both DMSO reductase and aspartate ammonia lyase (AspA) under anaerobic conditions. In a challenge experiment the A. pleuropneumoniae hlyX mutant is shown to be highly attenuated, unable to persist in healthy lung epithelium and tonsils, and impaired in survival inside sequestered lung tissue. Further, using an A. pleuropneumoniae strain carrying the luxAB genes as transcriptional fusion to aspA on the chromosome, the airway antioxidant glutathione was identified as one factor potentially responsible for inducing HlyX-dependent gene expression of A. pleuropneumoniae in epithelial lining fluid.
authors.affiliation: Institut fuer Mikrobiologie, Zentrum fuer Infektionsmedizin, Stiftung Tierärztliche Hochschule Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany. nbaltes@gmx.de
authors.forename: Nina
authors.initials: N
authors.lastname: Baltes
authors.forename: Mohamed
authors.initials: M
authors.lastname: N'diaye
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.forename: Alexander
authors.initials: A
authors.lastname: Maas
authors.forename: Falk F R
authors.initials: FF
authors.lastname: Buettner
authors.forename: Gerald-F
authors.initials: GF
authors.lastname: Gerlach
mesh_terms: D000189:Actinobacillus Infections / Q000378:metabolism* / Q000662:veterinary; D016977:Actinobacillus pleuropneumoniae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D000818:Animals; D001220:Aspartate Ammonia-Lyase / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D009154:Mutation; D012137:Respiratory System / Q000382:microbiology*; D013552:Swine; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C087924:HlyX protein, Actinobacillus pleuropneumoniae; D014157:Transcription Factors; D001220:Aspartate Ammonia-Lyase; D005978:Glutathione