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2015 ; 83
(6
): 2487-95
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Selective requirement of the shikimate pathway of Legionella pneumophila for
intravacuolar growth within human macrophages but not within Acanthamoeba
#MMPMID25847958
Jones SC
; Price CT
; Santic M
; Abu Kwaik Y
Infect Immun
2015[Jun]; 83
(6
): 2487-95
PMID25847958
show ga
Legionella pneumophila utilizes the Dot/Icm type IV translocation system to
proliferate within a vacuole in a wide variety of natural amoebal hosts and in
alveolar macrophages of the human accidental host. Although L. pneumophila
utilizes host amino acids as the main sources of carbon and energy, it is not
known whether de novo synthesis of amino acids by intravacuolar L. pneumophila
contributes to its nutrition. The aroB and aroE genes encode enzymes for the
shikimate pathway that generates the aromatic amino acids Phe, Trp, and Tyr. Here
we show the aroB and aroE mutants of L. pneumophila to be defective in growth in
human monocyte-derived macrophages (hMDMs) but not in Acanthamoeba spp. The aroB
and aroE mutants are severely attenuated in intrapulmonary proliferation in the
A/J mouse model of Legionnaires' disease, and the defect is fully complemented by
the respective wild-type alleles. The two mutants grow normally in rich media but
do not grow in defined media lacking aromatic amino acids, and the growth defect
is rescued by inclusion of the aromatic amino acids, which are essential for
production of the pyomelanin pigment. Interestingly, supplementation of infected
hMDMs with the three aromatic amino acids or with Trp alone rescues the
intramacrophage defect of the aroE but not the aroB mutant. Therefore, the
shikimate pathway of L. pneumophila is differentially required for optimal growth
within human macrophages, which are auxotrophic for Trp and Phe, but is
dispensable for growth within the Acanthamoeba spp. that synthesize the aromatic
amino acids.