Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator binding protein

Mohan, Sarbani; Hertweck, Christian; Dudda, Antje; Hammerschmidt, Sven; Skerka, Christine; Hallström, Teresia; Zipfel, Peter F.

doi:10.1016/j.molimm.2014.06.029

Cited by 59 publications

(58 citation statements)

References 80 publications

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“…Apart from Plg binding, cytoplasm-localized EFTu regulates protein synthesis and cellular metabolism by binding to and transporting amino-acyl-tRNA to the ribosomes confirming its RNA-binding ability44. Since EFTu, similarly to Eno, is associated with the cell wall of various bacteria414243, it is imaginable that other cytosolic proteins such as RNAPα and/or BglA3 may also be transported to the bacterial surface thereby acting as “moonlighting proteins” for eRNA-binding at certain steps of the growth phase.…”

Section: Discussionmentioning

confidence: 99%

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Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells

Zakrzewicz

Bergmann

Didiášová

et al. 2016

Sci Rep

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Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. The infection process involves bacterial cell surface receptors, which interact with host extracellular matrix components to facilitate colonization and dissemination of bacteria. Here, we investigated the role of host-derived extracellular RNA (eRNA) in the process of pneumococcal alveolar epithelial cell infection. Our study demonstrates that eRNA dose-dependently increased S. pneumoniae invasion of alveolar epithelial cells. Extracellular enolase (Eno), a plasminogen (Plg) receptor, was identified as a novel eRNA-binding protein on S. pneumoniae surface, and six Eno eRNA-binding sites including a C-terminal 15 amino acid motif containing lysine residue 434 were characterized. Although the substitution of lysine 434 for glycine (K434G) markedly diminished the binding of eRNA to Eno, the adherence to and internalization into alveolar epithelial cells of S. pneumoniae strain carrying the C-terminal lysine deletion and the mutation of internal Plg-binding motif were only marginally impaired. Accordingly, using a mass spectrometric approach, we identified seven novel eRNA-binding proteins in pneumococcal cell wall. Given the high number of eRNA-interacting proteins on pneumococci, treatment with RNase1 completely inhibited eRNA-mediated pneumococcal alveolar epithelial cell infection. Our data support further efforts to employ RNAse1 as an antimicrobial agent to combat pneumococcal infectious diseases.

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Section: Discussionmentioning

confidence: 99%

“…For instance, RNAPα and BglA3 possess C-terminal lysine residues. Although C-terminal lysine residue is absent in EFTu, this protein has been identified as a Plg receptor414243. Instead of C-terminal lysines, it seems that EFTu/Plg interaction occur via internal amino acid regions ( 179 LKALEGDSHYEDIV 192 and 249 VGIKEETQKAV 259 ).…”

Section: Discussionmentioning

confidence: 99%

Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells

Zakrzewicz

Bergmann

Didiášová

et al. 2016

Sci Rep

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“…We find Tse6 present at low levels in P. aeruginosa ; therefore, the yet lower levels within recipient cells would not sequester a functionally significant portion of EF-Tu. Indeed, there is growing evidence that the large pool of EF-Tu is exploited for multiple purposes within bacteria, including P. aeruginosa (Balasubramanian et al, 2008; Barel et al, 2008; Defeu Soufo et al, 2010; Kunert et al, 2007; Mohan et al, 2014). Barbier et al (2013) have found that EF-Tu PA is posttranslationally modified by trimethylation at Lys5.…”

Section: Discussionmentioning

confidence: 99%

An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

Whitney

Quentin

Sawai

et al. 2015

Cell

208

252

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SUMMARY Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD+ and NADP+. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tu (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.

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“…It is found on the surface of several pathogenic bacteria and is involved in adhesion, invasion, and modulation of the host immune system. 23,24,25,26,27,28,29,30,31 For example, surface EF-Tu of Mycoplasma pneumoniae serves as a fibronectin binding protein and facilitates the interaction with extracellular matrix. 27 Surface EF-Tu from Leptospira interrogans , Streptococcus pneumoniae , and Pseudomonas aeruginosa binds to the complement regulators factor H and plasminogen and has been proposed to contribute to tissue invasion and host immune evasion.…”

Section: Introductionmentioning

confidence: 99%

Borrelia burgdorferielongation factor EF-Tu is an immunogenic protein during Lyme borreliosis

Carrasco

Yang

Troxell

et al. 2015

Emerging Microbes & Infections

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Borrelia burgdorferi, the etiological agent of Lyme disease, does not produce lipopolysaccharide but expresses a large number of lipoproteins on its cell surface. These outer membrane lipoproteins are highly immunogenic and have been used for serodiagnosis of Lyme disease. Recent studies have shown that highly conserved cytosolic proteins such as enolase and elongation factor Tu (EF-Tu) unexpectedly localized on the surface of bacteria including B. burgdorferi, and surface-localized enolase has shown to contribute to the enzootic cycle of B. burgdorferi. In this study, we studied the immunogenicity, surface localization, and function of B. burgdorferi EF-Tu. We found that EF-Tu is highly immunogenic in mice, and EF-Tu antibodies were readily detected in Lyme disease patients. On the other hand, active immunization studies showed that EF-Tu antibodies did not protect mice from infection when challenged with B. burgdorferi via either needle inoculation or tick bites. Borrelial mouse-tick cycle studies showed that EF-Tu antibodies also did not block B. burgdorferi migration and survival in ticks. Consistent with these findings, we found that EF-Tu primarily localizes in the protoplasmic cylinder of spirochetes and is not on the surface of B. burgdorferi. Taken together, our studies suggest that B. burgdorferi EF-Tu is not surfaced exposed, but it is highly immunogenic and is a potential serodiagnostic marker for Lyme borreliosis.

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Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator binding protein

Cited by 59 publications

References 80 publications

Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells

Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells

An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

Borrelia burgdorferielongation factor EF-Tu is an immunogenic protein during Lyme borreliosis

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