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Infection and Immunity, July 2008, p. 3075-3085, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00209-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Significant Role for ladC in Initiation of Legionella pneumophila Infection{triangledown}

Hayley J. Newton,1,4 Fiona M. Sansom,1,4 Jenny Dao,3 Christel Cazalet,2 Holger Bruggemann,2 Christiane Albert-Weissenberger,2 Carmen Buchrieser,2 Nicholas P. Cianciotto,3 and Elizabeth L. Hartland1,4*

Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Victoria 3800, Australia,1 Biologie des Bactéries Intracellulaires, Institut Pasteur, and CNRS URA 2171, Paris Cedex 15, France,2 Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois 60611,3 Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia4

Received 14 February 2008/ Returned for modification 4 April 2008/ Accepted 9 April 2008

Previously, we identified ladC in a cohort of genes that were present in Legionella pneumophila but absent in other Legionella species. Here we constructed a ladC mutant of L. pneumophila and assessed its ability to replicate in mammalian cell lines and Acanthamoeba castellanii. The ladC mutant was recovered in significantly lower numbers than wild-type L. pneumophila at early time points, which was reversed upon transcomplementation with ladC but not ladCN430A/R434A, encoding a putative catalytically inactive derivative of the protein. In fact, complementation of ladC::Km with ladCN430A/R434A resulted in a severe replication defect within human and amoeba cell models of infection, which did not follow a typical dominant negative phenotype. Using differential immunofluorescence staining to distinguish adherent from intracellular bacteria, we found that the ladC mutant exhibited a 10-fold reduction in adherence to THP-1 macrophages but no difference in uptake by THP-1 cells. When tested in vivo in A/J mice, the competitive index of the ladC mutant dropped fivefold over 72 h, indicating a significant attenuation compared to wild-type L. pneumophila. Although localization of LadC to the bacterial inner membrane suggested that the protein may be involved in signaling pathways that regulate virulence gene expression, microarray analysis indicated that ladC does not influence the transcriptional profile of L. pneumophila in vitro or during A. castellanii infection. Although the mechanism by which LadC modulates the initial interaction between the bacterium and host cell remains unclear, we have established that LadC plays an important role in L. pneumophila infection.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. Phone: (61) 3 8344 8041. Fax: (61) 3 9347 1540. E-mail: Hartland{at}unimelb.edu.au

{triangledown} Published ahead of print on 21 April 2008.

Editor: J. L. Flynn

Infection and Immunity, July 2008, p. 3075-3085, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00209-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Al-Khodor, S., Kalachikov, S., Morozova, I., Price, C. T., Abu Kwaik, Y. (2009). The PmrA/PmrB Two-Component System of Legionella pneumophila Is a Global Regulator Required for Intracellular Replication within Macrophages and Protozoa. Infect. Immun. 77: 374-386 [Abstract] [Full Text]  


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