Legionella pneumophila catalase-peroxidases are required for proper trafficking and growth in primary macrophages

Purnima Bandyopadhyay, Brenda Byrne, Yolande Chan, Michele S. Swanson, Howard M. Steinman

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Legionella pneumophila, a parasite of aquatic amoebae and pathogen of pulmonary macrophages, replicates intracellularly, utilizing a type IV secretion system to subvert the trafficking of Legionella-containing phagosomes. Defense against host-derived reactive oxygen species has been proposed as critical for intracellular replication. Virulence traits of null mutants in katA and katB, encoding the two Legionella catalase-peroxidases, were analyzed to evaluate the hypothesis that L. pneumophila must decompose hydrogen peroxide to establish a replication niche in macrophages. Phagosomes containing katA or katB mutant Legionella colocalize with LAMP-1, a late endosomal-lysosomal marker, at twice the frequency of those of wild-type strain JR32 and show a decreased frequency of bacterial replication, in similarity to phenotypes of mutants with mutations in dotA and dotB, encoding components of the Type IV secretion system. Quantitative similarity of the katA/B phenotypes indicates that each contributes to virulence traits largely independently of intracellular compartmentalization (KatA in the periplasm and KatB in the cytosol). These data support a model in which KatA and KatB maintain a critically low level of H2O2 compatible with proper phagosome trafficking mediated by the type IV secretion apparatus. During these studies, we observed that dotA and dotB mutations in wild-type strain Lp02 had no effect on intracellular multiplication in the amoeba Acanthamoeba castellanii, indicating that certain dotA/B functions in Lp02 are dispensable in that experimental model. We also observed that wild-type JR32, unlike Lp02, shows minimal contact-dependent cytotoxicity, suggesting that cytotoxicity of JR32 is not a prerequisite for formation of replication-competent Legionella phagosomes in macrophages.

Original languageEnglish (US)
Pages (from-to)4526-4535
Number of pages10
JournalInfection and Immunity
Volume71
Issue number8
DOIs
StatePublished - Aug 1 2003

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Peroxidases
Legionella pneumophila
Legionella
Phagosomes
Catalase
Macrophages
Amoeba
Growth
Virulence
Acanthamoeba castellanii
Phenotype
Periplasm
Mutation
Alveolar Macrophages
Cytosol
Hydrogen Peroxide
Reactive Oxygen Species
Parasites
Theoretical Models
Type IV Secretion Systems

ASJC Scopus subject areas

  • Immunology

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Legionella pneumophila catalase-peroxidases are required for proper trafficking and growth in primary macrophages. / Bandyopadhyay, Purnima; Byrne, Brenda; Chan, Yolande; Swanson, Michele S.; Steinman, Howard M.

In: Infection and Immunity, Vol. 71, No. 8, 01.08.2003, p. 4526-4535.

Research output: Contribution to journalArticle

Bandyopadhyay, Purnima ; Byrne, Brenda ; Chan, Yolande ; Swanson, Michele S. ; Steinman, Howard M. / Legionella pneumophila catalase-peroxidases are required for proper trafficking and growth in primary macrophages. In: Infection and Immunity. 2003 ; Vol. 71, No. 8. pp. 4526-4535.
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