Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila

Abstract

dLegionella pneumophila is 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 the L. pneumophila strain 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 the L. pneumophila strain 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 deprivation in vitro. Moreover, LbtP is important for L. pneumophila growth 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 impair L. pneumophila growth in the amoebal host Acanthamoeba castellanii, demonstrating a host-specific requirement for the activities of these two transporters in iron acquisition. The growth defect of the ⌬lbtP mutant in macrophages is not due to alterations in growth kinetics. Instead, the absence of LbtP limits L. pneumophila replication 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 allows L. pneumophila to abandon the host cell when nutrients are exhausted.

Differential Effects of Iron, Zinc, and Copper on Dictyostelium discoideum Cell Growth and Resistance to Legionella pneumophila

“…Whether this is due to iron being secreted by the iron-overloaded cells, thus stimulating bacterial attachment to the cell surface, is unclear. Increased Legionella uptake due to extracellular iron has been recently described in macrophages (O'Connor et al, 2016 ).…”

A Clinical Overview of Hospital-Acquired Legionella Pneumonia: Prevention Is the Key?

“…Legionella's life cycle consists of two main phases. In order to survive against harsh environmental conditions, legionella enters a "reversible dormant state", known as the viable but not culturable state (VBNCS) [24] When environmental conditions improve, like in the case of phagocytosis by Acanthamoeba castellanii, the bacterium represses its virulent traits and goes into its exponential phase, in which it replicates within the protozoa [6]. This process of replication takes round 15 hours to complete [25].…”

“…Once lack of nutrients and environmental stress strikes, L. pneumophila coordinates its differentiation to the mature intracellular form (MIF) and the stationary phase form (SPFs), both with virulent traits characterized by high motility and cytotoxicity and proceeds to lyse the cell and infect cells in proximity. Although studies are lacking on the mechanisms by which the host cell is lysed by the bacterium [24,25]. SPFs present flagella, loose outer membrane, and a well-defined inner membrane, while MIFs typically appear as stubby rods with complex envelope, both being able to colonize alveolar macrophages [24].…”

“…Although studies are lacking on the mechanisms by which the host cell is lysed by the bacterium [24,25]. SPFs present flagella, loose outer membrane, and a well-defined inner membrane, while MIFs typically appear as stubby rods with complex envelope, both being able to colonize alveolar macrophages [24]. Legionella accomplishes this physiologic and morphologic change by the coordination of LetA/LetS and sigma factors RpoS and FiA [26].…”

“…CsrA expression represses the flagellar sigma factor fliA, which translates into a non-motile pathogen, with reduced virulence [27]. Studies have shown that through legionella's exponential phase, the bacterium increases its resistance against heat, and antibiotics [24].…”