Group A Streptococcal Surface GAPDH, SDH, Recognizes uPAR/CD87 as its Receptor on the Human Pharyngeal Cell and Mediates Bacterial Adherence to Host Cells

Jin, Hong; Song, Youngmia P.; Boël, Grégory; Kochar, Jaspreet; Pancholi, Vijay

doi:10.1016/j.jmb.2005.04.063

Cited by 107 publications

(90 citation statements)

References 55 publications

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“…We selected GAPDH for further analysis because: (i) GAPDH has recently been identified as a transferrin receptor in macrophages and numerous other cell types [26][27][28] , (ii) the highly conserved nature of the protein and (iii) its role as a virulence factor [29][30][31][32] .…”

Section: Resultsmentioning

confidence: 99%

“…Six interacting proteins were identified which included iron-regulated elongation factor tu (Rv0685), L-Lactate dehydrogenase (Rv1872c), acyl-carrier protein desaturase (Rv0824c), the 50S ribosomal proteins L1 (Rv0641), L2 (Rv0704) and glyceraldehyde-3-phosphate dehydrogenase (Rv1436). Of these proteins, homologues of elongation factor tu 36 , L-Lactate dehydrogenase 37 and ribosomal proteins 38 are known to be multifunctional in other organisms while GAPDH is known to be a virulence factor for several pathogens [29][30][31][32][33] . GAPDH has also been reported as a transferrin-binding protein in S. aureus and S. epidermidis 21 .…”

Section: Discussionmentioning

confidence: 99%

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Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

et al. 2014

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Mycobacterium tuberculosis (M.tb), which requires iron for survival, acquires this element by synthesizing iron-binding molecules known as siderophores and by recruiting a host iron-transport protein, transferrin, to the phagosome. The siderophores extract iron from transferrin and transport it into the bacterium. Here we describe an additional mechanism for iron acquisition, consisting of an M.tb protein that drives transport of human holo-transferrin into M.tb cells. The pathogenic strain M.tb H37Rv expresses several proteins that can bind human holo-transferrin. One of these proteins is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Rv1436), which is present on the surface of M.tb and its relative Mycobacterium smegmatis. Overexpression of GAPDH results in increased transferrin binding to M.tb cells and iron uptake. Human transferrin is internalized across the mycobacterial cell wall in a GAPDH-dependent manner within infected macrophages.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

et al. 2014

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“…Given its multiple binding specificities, GAPDH is therefore likely to make a significant contribution to the colonization capabilities of streptococci. Furthermore, GAPDH has been shown to interact with the pharyngeal cell cytoskeletal proteins actin and myosin (447,540) and with urokinase plasminogen activator receptor (277), factors that may contribute to the modulatory effects of GAPDH in triggering host cell internalization by GAS (as described elsewhere). In addition to their adhesive and glycolytic functions, another interesting property of the five anchorless enzymes described above is that they function as a complex in the production of ATP (164).…”

Section: Anchorless Adhesinsmentioning

confidence: 95%

StreptococcusAdherence and Colonization

Nobbs

Lamont

Jenkinson

2009

Microbiol Mol Biol Rev

552

569

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SUMMARY Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed.

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“…Human IgG-binding Assay-To determine changes in human immunoglobulin binding activity as a result of the deletion of CdhA/SibA/SPy0019, an hIgG-binding assay was carried out essentially as described previously with minor modifications (30). Briefly, wild-type, mutant, and cdhA-complemented GAS strains were suspended in 0.05 M Tris/HCl buffer, pH 8.0, containing 0.5% BSA to an A 600 of 1.00.…”

Section: Methodsmentioning

confidence: 99%

Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor

Pancholi

Boël²,

Jin

2010

Journal of Biological Chemistry

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Cell division and cell wall synthesis are closely linked complex phenomena and play a crucial role in the maintenance and regulation of bacterial virulence. Eukaryotic-type Ser/Thr kinases reported in prokaryotes, including that in group A Streptococcus (GAS) (Streptococcus pyogenes Ser/Thr kinase (SP-STK)), regulate cell division, growth, and virulence. The mechanism of this regulation is, however, unknown. In this study, we demonstrated that SP-STK-controlled cell division is mediated under the positive regulation of secretory protein that possesses a cysteine and histidine-dependent aminohydrolases/peptidases (CHAP) domain with functionally active cell wall hydrolase activity (henceforth named as CdhA (CHAP-domain-containing and chain-forming cell wall hydrolase). Deletion of the CdhA-encoding gene resulted in severe cell division and growth defects in GAS mutants. The mutant expressing the truncated CdhA (devoid of the CHAP domain), although displayed no such defects, it became attenuated for virulence in mice and highly susceptible to cell wall-acting antibiotics, as observed for the mutant lacking CdhA. When CdhA was overexpressed in the wild-type GAS as well as in heterologous strains, Escherichia coli and Staphylococcus aureus, we observed a distinct increase in bacterial chain length. Our data reveal that CdhA is a multifunctional protein with a major function of the N-terminal region as a cell division plane-recognizing domain and that of the C-terminal CHAP domain as a virulence-regulating domain. CdhA is thus an important therapeutic target.

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Group A Streptococcal Surface GAPDH, SDH, Recognizes uPAR/CD87 as its Receptor on the Human Pharyngeal Cell and Mediates Bacterial Adherence to Host Cells

Cited by 107 publications

References 55 publications

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

StreptococcusAdherence and Colonization

Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor

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