Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza

Park, Sang-Sang; Riegler, Ashleigh N.; Im, Hansol; Hale, Yvette; Platt, Maryann P.; Croney, Christina M.; Briles, David E.; Orihuela, Carlos J.

doi:10.1016/j.celrep.2021.109267

Cited by 30 publications

(33 citation statements)

References 64 publications

(73 reference statements)

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“…In in vivo experiments, co-infection appears to be adverse for the host, caused by the IAV induced expression of type I interferons suppressing the bacterial clearance by disturbed recruitment of immune cells ( LeMessurier et al., 2020 ; Park et al., 2021 ). On the other hand, type I interferons increase the expression of tight junction proteins and decrease the expression of PAFr, reducing pneumococcal uptake and hindering transmigration ( LeMessurier et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniae and Influenza A Virus Co-Infection Induces Altered Polyubiquitination in A549 Cells

Sura

Gering

Cammann

et al. 2022

Front. Cell. Infect. Microbiol.

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Epithelial cells are an important line of defense within the lung. Disruption of the epithelial barrier by pathogens enables the systemic dissemination of bacteria or viruses within the host leading to severe diseases with fatal outcomes. Thus, the lung epithelium can be damaged by seasonal and pandemic influenza A viruses. Influenza A virus infection induced dysregulation of the immune system is beneficial for the dissemination of bacteria to the lower respiratory tract, causing bacterial and viral co-infection. Host cells regulate protein homeostasis and the response to different perturbances, for instance provoked by infections, by post translational modification of proteins. Aside from protein phosphorylation, ubiquitination of proteins is an essential regulatory tool in virtually every cellular process such as protein homeostasis, host immune response, cell morphology, and in clearing of cytosolic pathogens. Here, we analyzed the proteome and ubiquitinome of A549 alveolar lung epithelial cells in response to infection by either Streptococcus pneumoniae D39Δcps or influenza A virus H1N1 as well as bacterial and viral co-infection. Pneumococcal infection induced alterations in the ubiquitination of proteins involved in the organization of the actin cytoskeleton and Rho GTPases, but had minor effects on the abundance of host proteins. H1N1 infection results in an anti-viral state of A549 cells. Finally, co-infection resembled the imprints of both infecting pathogens with a minor increase in the observed alterations in protein and ubiquitination abundance.

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Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniae and Influenza A Virus Co-Infection Induces Altered Polyubiquitination in A549 Cells

Sura

Gering

Cammann

et al. 2022

Front. Cell. Infect. Microbiol.

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“…A recent study has highlighted the role of mammalian cell surface recruited GAPDH in host pathogen interaction. Host GAPDH on surface of dying lung epithelial cells was found to interact with Strepococcus pneumoniae resulting in secondary infection following influenza infection [ 47 ]. This study demonstrated that endogenous GAPDH was recruited onto the surface of dying lung epithelial cells which had been infected with either, Influenza A virus (IAV) or Streptococcus pneumoniae .…”

Section: Discussionmentioning

confidence: 99%

Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells

et al. 2021

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Rapid clearance of apoptotic cells by phagocytes is crucial for organogenesis, tissue homeostasis, and resolution of inflammation. This process is initiated by surface exposure of various ‘eat me’ ligands. Though phosphatidylserine (PS) is the best recognized general recognition ligand till date, recent studies have shown that PS by itself is not sufficient for clearance of apoptotic cells. In this study, we have identified a specific pleioform of GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) that functions as an ‘eat me’ signal on apoptotic cell surface. This specific form of GAPDH which is exposed on surface of apoptotic cells was found to interact with CD14 present on plasma membrane of phagocytes leading to their engulfment. This is the first study demonstrating the novel interaction between multifunctional GAPDH and the phagocytic receptor CD14 resulting in apoptotic cell clearance (efferocytosis).

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“…In our studies that identified PspA as having affinity to lactate dehydrogenase and GAPDH, it was observed that PspA also had affinity to numerous other host proteins (Park et al, 2021a;Park et al, 2021b). Among these was the filamentous protein vimentin, which has been implicated as a key ligand for group B Streptococci and E. coli with regard to their ability to gain access to the central nervous system (Deng et al, 2019).…”

Section: Other Interactionsmentioning

confidence: 92%

“…Curates PC residues on pneumococcal surface (Gosink et al, 2000;Hermoso et al, 2005) Choline McDaniel et al, 1986;McDaniel et al, 1987;Shaper et al, 2004;Mukerji et al, 2012;Park et al, 2021a;Park et al, 2021b) Pneumococcal choline-binding protein A…”

Section: Name Abbreviation Functionmentioning

confidence: 99%

A Jack of All Trades: The Role of Pneumococcal Surface Protein A in the Pathogenesis of Streptococcus pneumoniae

Lane

Tata

Briles

et al. 2022

Front. Cell. Infect. Microbiol.

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Streptococcus pneumoniae (Spn), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. Spn is an opportunistic pathogen capable of life-threatening disease should it become established in the lungs, gain access to the bloodstream, or disseminate to vital organs including the central nervous system. Spn is encapsulated, allowing it to avoid phagocytosis, and current preventative measures against infection include polyvalent vaccines composed of capsular polysaccharide corresponding to its most prevalent serotypes. The pneumococcus also has a plethora of surface components that allow the bacteria to adhere to host cells, facilitate the evasion of the immune system, and obtain vital nutrients; one family of these are the choline-binding proteins (CBPs). Pneumococcal surface protein A (PspA) is one of the most abundant CBPs and confers protection against the host by inhibiting recognition by C-reactive protein and neutralizing the antimicrobial peptide lactoferricin. Recently our group has identified two new roles for PspA: binding to dying host cells via host-cell bound glyceraldehyde 3-phosphate dehydrogenase and co-opting of host lactate dehydrogenase to enhance lactate availability. These properties have been shown to influence Spn localization and enhance virulence in the lower airway, respectively. Herein, we review the impact of CBPs, and in particular PspA, on pneumococcal pathogenesis. We discuss the potential and limitations of using PspA as a conserved vaccine antigen in a conjugate vaccine formulation. PspA is a vital component of the pneumococcal virulence arsenal – therefore, understanding the molecular aspects of this protein is essential in understanding pneumococcal pathogenesis and utilizing PspA as a target for treating or preventing pneumococcal pneumonia.

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Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza

Cited by 30 publications

References 64 publications

Streptococcus pneumoniae and Influenza A Virus Co-Infection Induces Altered Polyubiquitination in A549 Cells

Streptococcus pneumoniae and Influenza A Virus Co-Infection Induces Altered Polyubiquitination in A549 Cells

Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells

A Jack of All Trades: The Role of Pneumococcal Surface Protein A in the Pathogenesis of Streptococcus pneumoniae

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