Heterogeneity in intracellular replication and cytopathogenicity of Legionella pneumophila and Legionella micdadei in mammalian and protozoan cells

In contrast to Legionella pneumophila, little is known about the pathogenes is of other legionellae species that are capable of causing Legionnaires' d isease. In this report, we contrast L. pneumophila and L. micdadei for thei r cytopathogenicity and intracellular replication within mammalian and prot ozoan cells. We show by transmission electron microscopy that L. micdadei r eplicates within an endoplasmic reticulum (RER)-free phagosome within human macrophages, alveolar epithelial cells, and within the protozoan Hartmanne lla vermiformis. In contrast, L. pneumophila replicates within a RER-surrou nded phagosome within the same host cells. In contrast to replication of L. pneumophila within Acanthamoebae polyphaga, L. micdadei does not replicate within this protozoan host. Despite the prolific intracellular replication , L. micdadei is less cytopathogenic to all host cells than L. pneumophila. Since both species replicate intracellularly to a similar level, we have e xamined whether the reduced cytopathogenicity of L. micdadei is due to a re duced capacity to induce apoptosis or pore formation-mediated necrosis, bot h of which contribute to killing of the host cell by L. pneumophila. The da ta show that both species induced apoptosis-mediated killing of mammalian c ells to a similar level. In contrast to L. pneumophila, expression of the p ore-forming toxin by L. micdadei and its necrotic effect on macrophages and alveolar epithelial cells is undetectable. This has been further confirmed showing that L. micdadei is completely defective in contact-dependent haem olysis of RBCs, an activity mediated by the pore-forming toxin. Finally, in contrast to L. pneumophila, there was no significant intrapulmonary replic ation of L. micdadei in the A/J mice animal model. Our data show dramatic d ifferences between L. pneumophila and L. micdadei in intracellular replicat ion, cytopathogenicity, and infectivity to mammalian and protozoan cells. ( C) 1999 Academic Press.