title: Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila.
abstract: Adaptation to the host environment and exploitation of host cell functions are critical to the success of intracellular pathogens. Here, insight to these virulence mechanisms was obtained for the first time from the transcriptional program of the human pathogen Legionella pneumophila during infection of its natural host, Acanthamoeba castellanii. The biphasic life cycle of L. pneumophila was reflected by a major shift in gene expression from replicative to transmissive phase, concerning nearly half of the genes predicted in the genome. However, three different L. pneumophila strains showed similar in vivo gene expression patterns, indicating that common regulatory mechanisms govern the Legionella life cycle, despite the plasticity of its genome. During the replicative phase, in addition to components of aerobic metabolism and amino acid catabolism, the Entner-Doudoroff pathway, a NADPH producing mechanism used for sugar and/or gluconate assimilation, was expressed, suggesting for the first time that intracellular L. pneumophila may also scavenge host carbohydrates as nutrients and not only proteins. Identification of genes only upregulated in vivo but not in vitro, may explain higher virulence of in vivo grown L. pneumophila. Late in the life cycle, L. pneumophila upregulates genes predicted to promote transmission and manipulation of a new host cell, therewith priming it for the next attack. These including substrates of the Dot/Icm secretion system, other factors associated previously with invasion and virulence, the motility and the type IV pilus machineries, and > 90 proteins not characterized so far. Analysis of a fliA (sigma28) deletion mutant identified genes coregulated with the flagellar regulon, including GGDEF/EAL regulators and factors that promote host cell entry and survival.
authors.affiliation: Unité de Génomique des Microorganismes Pathogènes and CNRS URA 2171, Paris, France.
authors.forename: Holger
authors.initials: H
authors.lastname: Brüggemann
authors.forename: Arne
authors.initials: A
authors.lastname: Hagman
authors.forename: Matthieu
authors.initials: M
authors.lastname: Jules
authors.forename: Odile
authors.initials: O
authors.lastname: Sismeiro
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dillies
authors.forename: Catherine
authors.initials: C
authors.lastname: Gouyette
authors.forename: Frank
authors.initials: F
authors.lastname: Kunst
authors.forename: Michael
authors.initials: M
authors.lastname: Steinert
authors.forename: Klaus
authors.initials: K
authors.lastname: Heuner
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D050260:Carbohydrate Metabolism; D004269:DNA, Bacterial / Q000235:genetics; D005407:Flagella / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D008954:Models, Biological; D010586:Phagocytes / Q000382:microbiology*; D018085:Regulon; D012808:Sigma Factor / Q000235:genetics; D013045:Species Specificity; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C064971:FliA protein, Bacteria; D012808:Sigma Factor