Abstract

Legionella pneumophila is a natural intracellular bacterial parasite of free-living freshwater protozoa and an accidental human pathogen that causes Legionnaires' disease. L. pneumophila differentiates, and does it in style. Recent experimental data on L. pneumophila's differentiation point at the existence of a complex network that involves many developmental forms. We intend readers to: (i) understand the biological relevance of L. pneumophila's forms found in freshwater and their potential to transmit Legionnaires' disease, and (ii) learn that the common depiction of L. pneumophila's differentiation as a biphasic developmental cycle that alternates between a replicative and a transmissive form is but an oversimplification of the actual process. Our specific objectives are to provide updates on the molecular factors that regulate L. pneumophila's differentiation (Section The Differentiation Process and Its Regulation), and describe the developmental network of L. pneumophila (Section Dissecting Lp's Developmental Network), which for clarity's sake we have dissected into five separate developmental cycles. Finally, since each developmental form seems to contribute differently to the human pathogenic process and the transmission of Legionnaires' disease, readers are presented with a challenge to develop novel methods to detect the various L. pneumophila forms present in water (Section Practical Implications), as a means to improve our assessment of risk and more effectively prevent legionellosis outbreaks.

Highlights

  • We showed that the Legionella pneumophila (Lp) progeny produced in Acanthamoeba castellanii is morphologically differentiated and infectious to cells in culture, whereas the progeny produced in human macrophages derived from the U937 or THP-1 cell lines was only partially differentiated and showed infectivity defects (Abdelhady and Garduño, 2013)

  • We reencountered the protein as one consistently induced to high levels in Lp cells placed in water, and later found that its expression was linked to the differentiation of Lp into transmissive forms (SPFs and Mature infectious form (MIF)) (Hiltz et al, 2004), with very high levels produced in MIFs (Garduño et al, 2002; Hiltz et al, 2004)

  • By comparing the published microarray data for the transcriptome of Lp grown in amoeba (Brüggemann et al, 2006) against that of Lp grown in macrophages (Faucher et al, 2011) we have identified a list of differentially expressed genes

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Summary

BACKGROUND

L. PNEUMOPHILA IS A FACULTATIVE INTRACELLULAR PATHOGEN THAT DIFFERENTIATES INTO NUMEROUS FORMS WITHIN A DEVELOPMENTAL NETWORK. Given the complexity of Lp’s ecology and the many developmental forms involved, we proposed the existence of a developmental network (Garduño et al, 2008). This developmental network includes the “accidental” hosts that support the intracellular growth of Lp in the context of laboratory investigations, or in the context of human Legionnaires’ disease. In the case of a multiphasic cycle, more than two forms would www.frontiersin.org

VBNCC derived from an EPF Pelleted MIFs Pelleted VBNCCs
Multiphasic network
THE DIFFERENTIATION PROCESS AND ITS REGULATION
Food vacuole environment
Mature infectious form Filament
Lung epithelial cell or macrophage
PRACTICAL IMPLICATIONS
Generic VBNC Stationary phase form
Human macrophagesb
CONCLUSION
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