Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila
Legionella pneumophilais an intracellular bacterial pathogen that replicates in alveolar macrophages, causing a severe form of pneumonia. Intracellular growth of the bacterium depends on its ability to sequester iron from the host cell. In theL. pneumophilastrain 130b, one mechanism used to acquire this essential nutrient is the siderophore legiobactin. Iron-bound legiobactin is imported by the transport protein LbtU. Here, we describe the role of LbtP, a paralog of LbtU, in iron acquisition in theL. pneumophilastrain Philadelphia-1. Similar to LbtU, LbtP is a siderophore transport protein and is required for robust growth under iron-limiting conditions. Despite their similar functions, however, LbtU and LbtP do not contribute equally to iron acquisition. The Philadelphia-1 strain lacking LbtP is more sensitive to iron deprivationin vitro. Moreover, LbtP is important forL. pneumophilagrowth within macrophages while LbtU is dispensable. These results demonstrate that LbtP plays a dominant role over LbtU in iron acquisition. In contrast, loss of both LbtP and LbtU does not impairL. pneumophilagrowth in the amoebal hostAcanthamoeba castellanii, demonstrating a host-specific requirement for the activities of these two transporters in iron acquisition. The growth defect of the ΔlbtPmutant in macrophages is not due to alterations in growth kinetics. Instead, the absence of LbtP limitsL. pneumophilareplication and causes bacteria to prematurely exit the host cell. These results demonstrate the existence of a preprogrammed exit strategy in response to iron limitation that allowsL. pneumophilato abandon the host cell when nutrients are exhausted.