Legionella pneumophila is a facultative intracellular bacterium, which upon inhalation can cause a potentially fatal
pneumonia termed
Legionnaires' disease. The opportunistic pathogen grows in environmental amoebae and mammalian macrophages within a unique membrane-bound compartment, the 'Legionella-containing vacuole'. Bacteria are exposed to many environmental cues including small signalling molecules from eukaryotic cells. A number of pathogenic bacteria sense and respond to
catecholamine hormones, such as adrenalin and noradrenalin, a process mediated via the QseBC two-component system in some bacteria. In this study, we examined the effect of
adrenergic compounds on L. pneumophila, and discovered that the
adrenergic receptor antagonists benoxathian,
naftopidil,
propranolol and
labetalol, as well as the QseC sensor
kinase inhibitor
LED209, reduced the growth of L. pneumophila in broth or amoebae, while replication in macrophages was enhanced. Growth restriction was common to members of the genus Legionella and Mycobacterium, and was observed for L. pneumophila in the replicative but not stationary phase of the biphasic life cycle. Deletion of the L. pneumophila qseBC genes indicated that growth inhibition by
adrenergics or
LED209 is mediated only to a minor extent by this two-component system, implying the presence of other
adrenergic sensing systems. This study identifies
adrenergic molecules as novel inhibitors of extra- and intracellular growth of Legionella and reveals
LED209 as a potential lead compound to combat
infections with Legionella or Mycobacterium spp.