Affiliation:
1. Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Abstract
ABSTRACT
Staphylococcus aureus
is a ubiquitous bacterial pathogen that is the causative agent of numerous acute and chronic infections.
S. aureus
colonizes the anterior nares of a significant portion of the healthy adult population, but the mechanisms of colonization remain incompletely defined. Sialic acid (
N
-acetylneuraminic acid [Neu5Ac]) is a bioavailable carbon and nitrogen source that is abundant on mucosal surfaces and in secretions in the commensal environment. Our findings demonstrate that Neu5Ac can serve as an
S. aureus
carbon source, and we have identified a previously uncharacterized chromosomal locus (
nan
) that is required for Neu5Ac utilization. Molecular characterization of the
nan
locus indicates that it contains five genes, organized into four transcripts, and the genes were renamed
nanE
,
nanR
,
nanK
,
nanA
, and
nanT
. Initial studies with gene deletions indicate that
nanT
, predicted to encode the Neu5Ac transporter, and
nanA
and
nanE
, predicted to encode catabolic enzymes, are essential for growth on Neu5Ac. Furthermore, a
nanE
deletion mutant exhibits a growth inhibition phenotype in the presence of Neu5Ac. Transcriptional fusions and Northern blot analyses indicate that NanR represses the expression of both the
nanAT
and
nanE
transcripts, which can be relieved with Neu5Ac. Electrophoretic mobility studies demonstrate that NanR binds to the
nanAT
and
nanE
promoter regions, and the Neu5Ac catabolic intermediate
N
-acetylmannosamine-6-phosphate (ManNAc-6P) relieves NanR promoter binding. Taken together, these data indicate that the
nan
gene cluster is essential for Neu5Ac utilization and may perform an important function for
S. aureus
survival in the host.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
75 articles.
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