Characterization of a novel sialic acid transporter of the sodium solute symporter (SSS) family and in vivo comparison with known bacterial sialic acid transporters

Severi, Emmanuele; Hosie, Arthur H.F.; Hawkhead, Judith A.; Thomas, Gavin H.

doi:10.1111/j.1574-6968.2009.01881.x

Cited by 45 publications

(94 citation statements)

References 31 publications

(57 reference statements)

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“…Based on annotation of the TIGR4 genome, three distinct genetic regions have been suggested to encode sialic acid transporters: a predicted sodium solute symporter, SP1328, and two predicted ABC transporters, SP1681-3 and SP1688-90 (Fig. 2) (2,27,32,35). Of these, the predicted sodium solute symporter (SP1328) was previously proposed to be the primary transporter (35).…”

Section: Resultsmentioning

confidence: 99%

Sialic Acid Transport Contributes to Pneumococcal Colonization

et al. 2011

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Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Airway colonization is a necessary precursor to disease, but little is known about how the bacteria establish and maintain colonization. Carbohydrates are required as a carbon source for pneumococcal growth and, therefore, for colonization. Free carbohydrates are not readily available in the naso-oropharynx; however, N-and O-linked glycans are common in the airway. Sialic acid is the most common terminal modification on N-and O-linked glycans and is likely encountered frequently by S. pneumoniae in the airway. Here we demonstrate that sialic acid supports pneumococcal growth when provided as a sole carbon source. Growth on sialic acid requires import into the bacterium. Three genetic regions have been proposed to encode pneumococcal sialic acid transporters: one sodium solute symporter and two ATP binding cassette (ABC) transporters. Data demonstrate that one of these, satABC, is required for transport of sialic acid. A satABC mutant displayed significantly reduced growth on both sialic acid and the human glycoprotein alpha-1. The importance of satABC for growth on human glycoprotein suggests that sialic acid transport may be important in vivo. Indeed, the satABC mutant was significantly reduced in colonization of the murine upper respiratory tract. This work demonstrates that S. pneumoniae is able to use sialic acid as a sole carbon source and that utilization of sialic acid is likely important during pneumococcal colonization.

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Section: Resultsmentioning

confidence: 99%

Sialic Acid Transport Contributes to Pneumococcal Colonization

et al. 2011

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“…1A), we often found them, with the notable exception of nanS, organized completely differently than in E. coli, including having locations near a putative transporter(s) in the sodium solute symporter family (1). One of these symporters was recently cloned from Salmonella enterica serovar Typhimurium and shown to complement an E. coli nanT mutant (41). These observations indicate that unlike E. coli, other enteric organisms are unable to metabolize Neu5,9Ac 2 (1) but have evolved sialic acid transporters that are functional only in the presence of phys-iological concentrations of sodium.…”

Section: Figurementioning

confidence: 99%

Control of the Escherichia coli Sialoregulon by Transcriptional Repressor NanR

2013

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NanR, one of >8,500 GntR superfamily helix-turn-helix transcriptional regulators, controls expression of the genes required for catabolism of sialic acids in Escherichia coli. It is predicted to do the same in related bacteria harboring orthologs of nanR. The sialic acids are a family of over 40 naturally occurring nine-carbon keto-sugar acids found mainly in the animal lineage, which includes starfish to humans in the deuterostome lineage. Sialic acids function in development, immunity, protein localization and stability, and homeostasis. They also serve as microbial carbon and nitrogen sources and ligands for cell recognition during host colonization. The importance of microbial sialic acid metabolism for host-microbe interactions has made it a target for therapeutic development. Exploiting this target depends on understanding sialometabolic pathways in a wide range of evolutionarily distinct bacteria. Here, we show by transcriptome, genetic, and biochemical analyses that the most common sialic acid, N-acetylneuraminate, induces the nanATEK-yhcH, yjhATS (nanCMS), and yjhBC operons by directly inactivating NanR, converting the predominantly dimeric form of the repressor to an inactive monomer of approximately 30-kDa. Additionally, other results identify critical amino acid residues and nucleotides in the regulator and operator, respectively. The combined results better define how sialic acids, acting through NanR, affect the metabolic flux of an important group of host-derived metabolites. Thus, E. coli serves as a valuable model for understanding sialocatabolic pathways in bacteria.

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“…Among bacteria, four diverse families of sialic acid transporters (SATs) can be genetically linked with the SAC cluster. The tripartite ATP-independent periplasmic (TRAP) transporter first characterized in Haemophilus influenzae is the predominant type in Pasteurellaceae and Vibrionaceae, the major facilitator superfamily (MFS) NanT is found mainly in Enterobacteriaceae, an ATP-binding cassette (ABC)-type transporter from Haemophilus ducreyi and the sodium solute symporter (SSS) first characterized in Salmonella enterica serovar Typhimurium are predominant among Firmicutes (Allen et al, 2005;Müller et al, 2006;AlmagroMoreno & Boyd, 2009a;Fischer et al, 2010;Severi et al, 2007Severi et al, , 2010Vimr et al, 2004).…”

Section: Introductionmentioning

confidence: 99%