Affiliation:
1. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
Abstract
ABSTRACT
The phagosomal transporter (Pht) family of the major facilitator superfamily (MFS) is encoded by phylogenetically related intracellular gammaproteobacteria, including the opportunistic pathogen
Legionella pneumophila
. The location of the
pht
genes between the putative thymidine kinase (
tdk
) and phosphopentomutase (
deoB
) genes suggested that the
phtC
and
phtD
loci contribute to thymidine salvage in
L. pneumophila
. Indeed, a
phtC
+
allele in
trans
restored pyrimidine uptake to an
Escherichia coli
mutant that lacked all known nucleoside transporters, whereas a
phtD
+
allele did not. The results of phenotypic analyses of
L. pneumophila
strains lacking
phtC
or
phtD
strongly indicate that
L. pneumophila
requires PhtC and PhtD function under conditions where sustained dTMP synthesis is compromised. First, in broth cultures that mimicked thymidine limitation or starvation,
L. pneumophila
exhibited a marked requirement for PhtC function. Conversely, mutation of
phtD
conferred a survival advantage. Second, in medium that lacked thymidine, multicopy
phtC
+
or
phtD
+
alleles enhanced the survival of
L. pneumophila
thymidylate synthase (
thyA
)-deficient strains, which cannot synthesize dTMP endogenously. Third, under conditions in which transport of the pyrimidine nucleoside analog 5-fluorodeoxyuridine (FUdR) would inhibit growth, PhtC and PhtD conferred a growth advantage to
L. pneumophila
thyA
+
strains. Finally, when cultured in macrophages,
L. pneumophila
required the
phtC-phtD
locus to replicate. Accordingly, we propose that PhtC and PhtD contribute to protect
L. pneumophila
from dTMP starvation during its intracellular life cycle.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
18 articles.
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