Regulation of sialic acid transport and catabolism in Haemophilus influenzae
Abstract
Summary: Virulence of nontypeable Haemophilus influenzae (NTHi) is dependent on the decoration of lipooligosaccharide with sialic acid. This sugar must be derived from the host, as NTHi cannot synthesize sialic acids. NTHi can also use sialic acid as a carbon source. The genes encoding the sialic acid transporter and the genes encoding the catabolic activities are localized to two divergently transcribed operons, the siaPT operon and the nan operon respectively. In this study, we identified SiaR as a repressor of sialic acid transport and catabolism in NTHi. Inactivation of siaR resulted in the unregulated expression of the genes in both operons. Unregulated catabolism of sialic acid in the siaR mutant resulted in the reduction of surface sialylation and an increase in serum sensitivity. In addition to SiaR‐mediated repression, CRP, the cAMP receptor protein, was shown to activate expression of the siaPT operon but not the nan operon. We describe a model in which SiaR and CRP work to modulate intracellular sialic acid levels. Our results demonstrate the importance of SiaR‐mediated regulation to balance the requirement of surface sialylation and the toxic accumulation of intracellular sialic acid.
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“These mechanisms range from the simple acquisition of host sialoglycans (997) to the direct transfer of host sialic acids by trans-sialidases (998), to the highly efficient uptake of the small amounts of environmental free sialic acids (999) or even the direct utilization of trace amounts of CMP sialic acid present in…”
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- Authors
- Johnston, J. W., Zaleski, A., Allen, S., Mootz, J. M., Armbruster, D., Gibson, B. W., Apicella, M. A., & Munson, R. S.
- Affiliations
- University of Iowa (US)
- Buck Institute for Research on Aging (US)
- Medical University of South Carolina (US)
- Abigail Wexner Research Institute (US)
- Corresponding author
- Apicella, Michael A.
- ORCID
- Gibson, Bradford W.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2007-09-14
- Volume
- 66
- Issue
- 1
- Pages
- 26-39
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1969225411
- Cited by
- 64
- References
- 33
- Citations by year
- 2026: 5 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 9 · 2012: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI 24616, AI30040)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- nontypeable Haemophilus influenzae, sialic acid transport, sialic acid catabolism, C-reactive protein, cAMP receptor protein, virulence, serum sensitivity, gene expression regulation
- MeSH terms
- Bacterial Proteins, Biological Transport, Blood Bactericidal Activity, Cyclic AMP Receptor Protein, DNA-Binding Proteins, DNA, Bacterial, Gene Expression Regulation, Haemophilus influenzae, Lipopolysaccharides, Protein Binding, Repressor Proteins, Transcription Factors, Colony Count, Microbial, Gene Expression Regulation, Bacterial, Mutagenesis, Insertional, Gene Deletion, DNA Footprinting, N-Acetylneuraminic Acid, Electrophoretic Mobility Shift Assay
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