While the majority of Legionnaire's disease has been attributed to Legionel
la pneumophila, Legionella micdadei can cause a similar infection in immuno
compromised people. Consistent with its epidemiological profile, the growth
of L. micdadei in cultured macrophages is less robust than that oft. pneum
ophila. To identify those features of the Legionella spp, which are correla
ted, 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 corre
lated with the virulence of L. pneumophila were evaluated: infection and re
plication in cultured macrophages, evasion of phagosome-lysosome fusion, co
ntact-dependent cytotoxicity, sodium sensitivity, osmotic resistance, and c
onjugal DNA transfer. By nearly every measure, L, micdadei appeared less vi
rulent than L. pneumophila. The surprising exception was L. micdadei 31B, w
hich evaded lysosomes and replicated in macrophages as efficiently as L. pn
eumophila, despite lacking both contact-dependent cytopathicity and regulat
ed sodium sensitivity. Second, in an attempt to identify virulence factors
genetically, an L. pneumophila genomic library was screened for clones whic
h conferred robust intracellular growth on L. micdadei, No such loci were i
solated, consistent with the multiple phenotypic differences observed for t
he two species. Apparently, L. pneumophila and L. micdadei use distinct str
ategies to colonize alveolar macrophages, causing Legionnaire's disease.