Iron limitation triggers early egress by the intracellular bacterial pathogen legionella pneumophila

Tamara J. O'Connor, Huaixin Zheng, Susan M. VanRheenen, Soma Ghosh, Nicholas P. Cianciotto, Ralph R. Isberg

Research output: Research - peer-reviewArticle

Abstract

Legionella 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 δlbtP 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.

LanguageEnglish (US)
Pages2185-2197
Number of pages13
JournalInfection and Immunity
Volume84
Issue number8
DOIs
StatePublished - 2016

Fingerprint

Legionella pneumophila
Iron
Growth
Siderophores
Carrier Proteins
Macrophages
Bacteria
Food
Acanthamoeba castellanii
Alveolar Macrophages
Pneumonia
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

O'Connor, T. J., Zheng, H., VanRheenen, S. M., Ghosh, S., Cianciotto, N. P., & Isberg, R. R. (2016). Iron limitation triggers early egress by the intracellular bacterial pathogen legionella pneumophila. Infection and Immunity, 84(8), 2185-2197. DOI: 10.1128/IAI.01306-15

Iron limitation triggers early egress by the intracellular bacterial pathogen legionella pneumophila. / O'Connor, Tamara J.; Zheng, Huaixin; VanRheenen, Susan M.; Ghosh, Soma; Cianciotto, Nicholas P.; Isberg, Ralph R.

In: Infection and Immunity, Vol. 84, No. 8, 2016, p. 2185-2197.

Research output: Research - peer-reviewArticle

O'Connor, TJ, Zheng, H, VanRheenen, SM, Ghosh, S, Cianciotto, NP & Isberg, RR 2016, 'Iron limitation triggers early egress by the intracellular bacterial pathogen legionella pneumophila' Infection and Immunity, vol 84, no. 8, pp. 2185-2197. DOI: 10.1128/IAI.01306-15
O'Connor TJ, Zheng H, VanRheenen SM, Ghosh S, Cianciotto NP, Isberg RR. Iron limitation triggers early egress by the intracellular bacterial pathogen legionella pneumophila. Infection and Immunity. 2016;84(8):2185-2197. Available from, DOI: 10.1128/IAI.01306-15
O'Connor, Tamara J. ; Zheng, Huaixin ; VanRheenen, Susan M. ; Ghosh, Soma ; Cianciotto, Nicholas P. ; Isberg, Ralph R./ Iron limitation triggers early egress by the intracellular bacterial pathogen legionella pneumophila. In: Infection and Immunity. 2016 ; Vol. 84, No. 8. pp. 2185-2197
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