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Modulation of host signaling and cellular responses by Chlamydia.

Mehlitz A, Rudel T - Cell Commun. Signal (2013)

Bottom Line: Growth in such a preferred niche comes at the price of an ongoing competition between the bacteria and the host as well as other microbes that compete for the very same host resources.This requires specialization and constant evolution of dedicated systems for adhesion, invasion and accommodation.Interestingly, obligate intracellular bacteria of the order Chlamydiales have evolved an impressive degree of control over several important host cell functions.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Wuerzburg, Biocenter, Department of Microbiology, Am Hubland, D-97074, Wuerzburg, Germany. thomas.rudel@biozentrum.uni-wuerzburg.de.

ABSTRACT
Modulation of host cell signaling and cellular functions is key to intracellular survival of pathogenic bacteria. Intracellular growth has several advantages e.g. escape from the humoral immune response and access to a stable nutrient rich environment. Growth in such a preferred niche comes at the price of an ongoing competition between the bacteria and the host as well as other microbes that compete for the very same host resources. This requires specialization and constant evolution of dedicated systems for adhesion, invasion and accommodation. Interestingly, obligate intracellular bacteria of the order Chlamydiales have evolved an impressive degree of control over several important host cell functions. In this review we summarize how Chlamydia controls its host cell with a special focus on signal transduction and cellular modulation.

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Adhesion induced signaling. A, Adhesin-receptor pairs are ill defined for the closely related pathogens C. trachomatis and C. muridarum. Several surface proteins like lipopolysaccharide (LPS), major outer membrane protein (MOMP), outer membrane complex B (OmcB) and polymorphic membrane protein (Pmp21) have been suggested as potential bacterial adhesins. A trimolecular bridge is thought to connect MOMP, OmcB and FGFR to their host or bacterial counterpart, respectively. Binding to host receptors like fibroblast growth factor receptor (FGFR) or platelet derived growth factor receptor (PDGFR) induces mitogenic signaling via extracellular-signal-regulated kinase 1/2 (Erk1/2). Receptor surface presentation and folding via protein disulfide isomerase (PDI) shows the necessity for specific host receptor binding. B, C. pneumoniae binds to its host cell in a bimolecular fashion via OmcB heparin sufate proteoglycan (HSPG) interaction. Binding between OmcB and HSPG is probably a reversible initial reversible binding step followed by irreversible specific binding. One adhesin receptor pair involved is Pmp21 – EGFR. The Pmp21 – EGFR interaction then triggers invasion of Chlamydia. Further, binding to EGFR also recruits growth factor receptor bound 2 (Grb2), Cas-Br-M (murine) ecotropic retroviral transforming sequence (c-Cbl), SHC (Src homology 2 domain containing) transforming protein 1 (SHC1) and phosphatidyl-inositol-3-kinase (PI3K) signaling, which initiates mitogenic Erk1/2 signaling as well as cytoskeletal rearrangements via focal adhesion kinase (FAK). Pmp6 and 20 have been suggested as additional adhesins on the bacterial side, while insulin growth factor receptor (IGFR) has been indicated on the host side.
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Figure 1: Adhesion induced signaling. A, Adhesin-receptor pairs are ill defined for the closely related pathogens C. trachomatis and C. muridarum. Several surface proteins like lipopolysaccharide (LPS), major outer membrane protein (MOMP), outer membrane complex B (OmcB) and polymorphic membrane protein (Pmp21) have been suggested as potential bacterial adhesins. A trimolecular bridge is thought to connect MOMP, OmcB and FGFR to their host or bacterial counterpart, respectively. Binding to host receptors like fibroblast growth factor receptor (FGFR) or platelet derived growth factor receptor (PDGFR) induces mitogenic signaling via extracellular-signal-regulated kinase 1/2 (Erk1/2). Receptor surface presentation and folding via protein disulfide isomerase (PDI) shows the necessity for specific host receptor binding. B, C. pneumoniae binds to its host cell in a bimolecular fashion via OmcB heparin sufate proteoglycan (HSPG) interaction. Binding between OmcB and HSPG is probably a reversible initial reversible binding step followed by irreversible specific binding. One adhesin receptor pair involved is Pmp21 – EGFR. The Pmp21 – EGFR interaction then triggers invasion of Chlamydia. Further, binding to EGFR also recruits growth factor receptor bound 2 (Grb2), Cas-Br-M (murine) ecotropic retroviral transforming sequence (c-Cbl), SHC (Src homology 2 domain containing) transforming protein 1 (SHC1) and phosphatidyl-inositol-3-kinase (PI3K) signaling, which initiates mitogenic Erk1/2 signaling as well as cytoskeletal rearrangements via focal adhesion kinase (FAK). Pmp6 and 20 have been suggested as additional adhesins on the bacterial side, while insulin growth factor receptor (IGFR) has been indicated on the host side.

Mentions: Efficient adhesion to host cells is a prerequisite for invasion and intracellular life and usually requires several adhesins. Chlamydia has evolved a number of ways to attach to various host cells and infect different tissues according to serovariant and species [29,30]. Early research focused on the role of the abundant major outer membrane protein (MOMP) as an adhesin [31] (Figure 1A-B). Blocking the exposed variable MOMP domains using specific antibodies disturbed binding to the host cell [32]. Chlamydia muridarum MOMP has been described to mediate attachment to host cells as a cytoadhesin [33]. Further, MOMP from various chlamydial species is glycosylated (mainly D-mannose-rich) and this modification is critical for MOMP adhesion [34-36]. The mannose-6-phosphate / insulin-like growth factor receptor 2 (M6PR/IGFR2) has been suggested as the host receptor for MOMP, since the MOMP glycan moiety is similar to the M6PR ligand mannose-6-phosphate and blocking the M6PR prevents C. pneumoniae attachment and invasion [37].


Modulation of host signaling and cellular responses by Chlamydia.

Mehlitz A, Rudel T - Cell Commun. Signal (2013)

Adhesion induced signaling. A, Adhesin-receptor pairs are ill defined for the closely related pathogens C. trachomatis and C. muridarum. Several surface proteins like lipopolysaccharide (LPS), major outer membrane protein (MOMP), outer membrane complex B (OmcB) and polymorphic membrane protein (Pmp21) have been suggested as potential bacterial adhesins. A trimolecular bridge is thought to connect MOMP, OmcB and FGFR to their host or bacterial counterpart, respectively. Binding to host receptors like fibroblast growth factor receptor (FGFR) or platelet derived growth factor receptor (PDGFR) induces mitogenic signaling via extracellular-signal-regulated kinase 1/2 (Erk1/2). Receptor surface presentation and folding via protein disulfide isomerase (PDI) shows the necessity for specific host receptor binding. B, C. pneumoniae binds to its host cell in a bimolecular fashion via OmcB heparin sufate proteoglycan (HSPG) interaction. Binding between OmcB and HSPG is probably a reversible initial reversible binding step followed by irreversible specific binding. One adhesin receptor pair involved is Pmp21 – EGFR. The Pmp21 – EGFR interaction then triggers invasion of Chlamydia. Further, binding to EGFR also recruits growth factor receptor bound 2 (Grb2), Cas-Br-M (murine) ecotropic retroviral transforming sequence (c-Cbl), SHC (Src homology 2 domain containing) transforming protein 1 (SHC1) and phosphatidyl-inositol-3-kinase (PI3K) signaling, which initiates mitogenic Erk1/2 signaling as well as cytoskeletal rearrangements via focal adhesion kinase (FAK). Pmp6 and 20 have been suggested as additional adhesins on the bacterial side, while insulin growth factor receptor (IGFR) has been indicated on the host side.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222901&req=5

Figure 1: Adhesion induced signaling. A, Adhesin-receptor pairs are ill defined for the closely related pathogens C. trachomatis and C. muridarum. Several surface proteins like lipopolysaccharide (LPS), major outer membrane protein (MOMP), outer membrane complex B (OmcB) and polymorphic membrane protein (Pmp21) have been suggested as potential bacterial adhesins. A trimolecular bridge is thought to connect MOMP, OmcB and FGFR to their host or bacterial counterpart, respectively. Binding to host receptors like fibroblast growth factor receptor (FGFR) or platelet derived growth factor receptor (PDGFR) induces mitogenic signaling via extracellular-signal-regulated kinase 1/2 (Erk1/2). Receptor surface presentation and folding via protein disulfide isomerase (PDI) shows the necessity for specific host receptor binding. B, C. pneumoniae binds to its host cell in a bimolecular fashion via OmcB heparin sufate proteoglycan (HSPG) interaction. Binding between OmcB and HSPG is probably a reversible initial reversible binding step followed by irreversible specific binding. One adhesin receptor pair involved is Pmp21 – EGFR. The Pmp21 – EGFR interaction then triggers invasion of Chlamydia. Further, binding to EGFR also recruits growth factor receptor bound 2 (Grb2), Cas-Br-M (murine) ecotropic retroviral transforming sequence (c-Cbl), SHC (Src homology 2 domain containing) transforming protein 1 (SHC1) and phosphatidyl-inositol-3-kinase (PI3K) signaling, which initiates mitogenic Erk1/2 signaling as well as cytoskeletal rearrangements via focal adhesion kinase (FAK). Pmp6 and 20 have been suggested as additional adhesins on the bacterial side, while insulin growth factor receptor (IGFR) has been indicated on the host side.
Mentions: Efficient adhesion to host cells is a prerequisite for invasion and intracellular life and usually requires several adhesins. Chlamydia has evolved a number of ways to attach to various host cells and infect different tissues according to serovariant and species [29,30]. Early research focused on the role of the abundant major outer membrane protein (MOMP) as an adhesin [31] (Figure 1A-B). Blocking the exposed variable MOMP domains using specific antibodies disturbed binding to the host cell [32]. Chlamydia muridarum MOMP has been described to mediate attachment to host cells as a cytoadhesin [33]. Further, MOMP from various chlamydial species is glycosylated (mainly D-mannose-rich) and this modification is critical for MOMP adhesion [34-36]. The mannose-6-phosphate / insulin-like growth factor receptor 2 (M6PR/IGFR2) has been suggested as the host receptor for MOMP, since the MOMP glycan moiety is similar to the M6PR ligand mannose-6-phosphate and blocking the M6PR prevents C. pneumoniae attachment and invasion [37].

Bottom Line: Growth in such a preferred niche comes at the price of an ongoing competition between the bacteria and the host as well as other microbes that compete for the very same host resources.This requires specialization and constant evolution of dedicated systems for adhesion, invasion and accommodation.Interestingly, obligate intracellular bacteria of the order Chlamydiales have evolved an impressive degree of control over several important host cell functions.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Wuerzburg, Biocenter, Department of Microbiology, Am Hubland, D-97074, Wuerzburg, Germany. thomas.rudel@biozentrum.uni-wuerzburg.de.

ABSTRACT
Modulation of host cell signaling and cellular functions is key to intracellular survival of pathogenic bacteria. Intracellular growth has several advantages e.g. escape from the humoral immune response and access to a stable nutrient rich environment. Growth in such a preferred niche comes at the price of an ongoing competition between the bacteria and the host as well as other microbes that compete for the very same host resources. This requires specialization and constant evolution of dedicated systems for adhesion, invasion and accommodation. Interestingly, obligate intracellular bacteria of the order Chlamydiales have evolved an impressive degree of control over several important host cell functions. In this review we summarize how Chlamydia controls its host cell with a special focus on signal transduction and cellular modulation.

Show MeSH
Related in: MedlinePlus