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Comparative analysis of Legionella pneumophila and Legionella micdadei virulence traits
1Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Abstract:
While the majority of Legionnaire's disease has been attributed to Legionella pneumophila, Legionella micdadei can cause a similar infection in immunocompromised people. Consistent with its epidemiological profile, the growth of L. micdadei in cultured macrophages is less robust than that of L. pneumophila. To identify those features of the Legionella spp. which are correlated to efficient growth in macrophages, two approaches were taken. First, a phenotypic analysis compared four clinical isolates of L. micdadei to one well-characterized strain of L. pneumophila. Seven traits previously correlated with the virulence of L. pneumophila were evaluated: infection and replication in cultured macrophages, evasion of phagosome-lysosome fusion, contact-dependent cytotoxicity, sodium sensitivity, osmotic resistance, and conjugal DNA transfer. By nearly every measure, L. micdadei appeared less virulent than L. pneumophila. The surprising exception was L. micdadei 31B, which evaded lysosomes and replicated in macrophages as efficiently as L. pneumophila, despite lacking both contact-dependent cytopathicity and regulated sodium sensitivity. Second, in an attempt to identify virulence factors genetically, an L. pneumophila genomic library was screened for clones which conferred robust intracellular growth on L. micdadei. No such loci were isolated, consistent with the multiple phenotypic differences observed for the two species. Apparently, L. pneumophila and L. micdadei use distinct strategies to colonize alveolar macrophages, causing Legionnaire's disease.
Insights
Legionella micdadei causes Legionnaire's disease in immunocompromised individuals, with one strain showing robust macrophage growth similar to Legionella pneumophila. These bacteria utilize distinct strategies for colonizing macrophages.
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Legionnaire's disease is primarily caused by Legionella pneumophila.
- Legionella micdadei is an opportunistic pathogen that can cause similar infections, particularly in immunocompromised individuals.
- L. micdadei exhibits less robust growth in macrophages compared to L. pneumophila.
Purpose of the Study:
- To identify bacterial features correlated with efficient intracellular growth in macrophages.
- To compare the virulence traits of L. micdadei and L. pneumophila.
Main Methods:
- Phenotypic analysis of four L. micdadei clinical isolates against L. pneumophila, evaluating traits like macrophage infection, replication, phagosome-lysosome fusion evasion, cytotoxicity, and osmotic resistance.
- Screening of an L. pneumophila genomic library for clones that enhance L. micdadei intracellular growth.
Main Results:
- Most L. micdadei isolates were less virulent than L. pneumophila across evaluated traits.
- A notable exception, L. micdadei 31B, demonstrated efficient macrophage evasion and replication comparable to L. pneumophila.
- This strain (31B) lacked contact-dependent cytopathicity and regulated sodium sensitivity, suggesting alternative virulence mechanisms.
- Genetic screening did not identify L. pneumophila loci conferring robust intracellular growth on L. micdadei.
Conclusions:
- L. pneumophila and L. micdadei employ distinct strategies for colonizing alveolar macrophages.
- Virulence in Legionella species is multifactorial and can vary significantly between species and even strains.