The Cell Wall Protein CwpV is
Antigenically Variable between Strains, but Exhibits Conserved
Aggregation-Promoting Function
Clostridium difficile is the main cause of antibiotic-associated
diarrhea, leading to significant morbidity and mortality and putting
considerable economic pressure on healthcare systems. Current knowledge of the
molecular basis of pathogenesis is limited primarily to the activities and
regulation of two major toxins. In contrast, little is known of mechanisms used
in colonization of the enteric system. C. difficile expresses a
proteinaceous array on its cell surface known as the S-layer, consisting
primarily of the major S-layer protein SlpA and a family of SlpA homologues, the
cell wall protein (CWP) family. CwpV is the largest member of this family and is
expressed in a phase variable manner. Here we show CwpV promotes C.
difficile aggregation, mediated by the C-terminal repetitive
domain. This domain varies markedly between strains; five distinct repeat types
were identified and were shown to be antigenically distinct. Other aspects of
CwpV are, however, conserved. All CwpV types are expressed in a phase variable
manner. Using targeted gene knock-out, we show that a single site-specific
recombinase RecV is required for CwpV phase variation. CwpV is
post-translationally cleaved at a conserved site leading to formation of a
complex of cleavage products. The highly conserved N-terminus anchors the CwpV
complex to the cell surface. Therefore CwpV function, regulation and processing
are highly conserved across C. difficile strains, whilst the
functional domain exists in at least five antigenically distinct forms. This
hints at a complex evolutionary history for CwpV.
Vyšlo v časopise:
The Cell Wall Protein CwpV is
Antigenically Variable between Strains, but Exhibits Conserved
Aggregation-Promoting Function. PLoS Pathog 7(4): e32767. doi:10.1371/journal.ppat.1002024
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002024
Souhrn
Clostridium difficile is the main cause of antibiotic-associated
diarrhea, leading to significant morbidity and mortality and putting
considerable economic pressure on healthcare systems. Current knowledge of the
molecular basis of pathogenesis is limited primarily to the activities and
regulation of two major toxins. In contrast, little is known of mechanisms used
in colonization of the enteric system. C. difficile expresses a
proteinaceous array on its cell surface known as the S-layer, consisting
primarily of the major S-layer protein SlpA and a family of SlpA homologues, the
cell wall protein (CWP) family. CwpV is the largest member of this family and is
expressed in a phase variable manner. Here we show CwpV promotes C.
difficile aggregation, mediated by the C-terminal repetitive
domain. This domain varies markedly between strains; five distinct repeat types
were identified and were shown to be antigenically distinct. Other aspects of
CwpV are, however, conserved. All CwpV types are expressed in a phase variable
manner. Using targeted gene knock-out, we show that a single site-specific
recombinase RecV is required for CwpV phase variation. CwpV is
post-translationally cleaved at a conserved site leading to formation of a
complex of cleavage products. The highly conserved N-terminus anchors the CwpV
complex to the cell surface. Therefore CwpV function, regulation and processing
are highly conserved across C. difficile strains, whilst the
functional domain exists in at least five antigenically distinct forms. This
hints at a complex evolutionary history for CwpV.
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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