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2015 ; 10
(9
): e0138244
Nephropedia Template TP
gab.com Text
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English Wikipedia
Analysis of the Mycoplasma genitalium MgpB Adhesin to Predict Membrane Topology,
Investigate Antibody Accessibility, Characterize Amino Acid Diversity, and
Identify Functional and Immunogenic Epitopes
#MMPMID26381903
Iverson-Cabral SL
; Wood GE
; Totten PA
PLoS One
2015[]; 10
(9
): e0138244
PMID26381903
show ga
Mycoplasma genitalium is a sexually transmitted pathogen and is associated with
reproductive tract disease that can be chronic in nature despite the induction of
a strong antibody response. Persistent infection exacerbates the likelihood of
transmission, increases the risk of ascension to the upper tract, and suggests
that M. genitalium may possess immune evasion mechanism(s). Antibodies from
infected patients predominantly target the MgpB adhesin, which is encoded by a
gene that recombines with homologous donor sequences, thereby generating sequence
variation within and among strains. We have previously characterized mgpB
heterogeneity over the course of persistent infection and have correlated the
induction of variant-specific antibodies with the loss of that particular variant
from the infected host. In the current study, we examined the membrane topology,
antibody accessibility, distribution of amino acid diversity, and the location of
functional and antigenic epitopes within the MgpB adhesin. Our results indicate
that MgpB contains a single transmembrane domain, that the majority of the
protein is surface exposed and antibody accessible, and that the attachment
domain is located within the extracellular C-terminus. Not unexpectedly, amino
acid diversity was concentrated within and around the three previously defined
variable regions (B, EF, and G) of MgpB; while nonsynonymous mutations were twice
as frequent as synonymous mutations in regions B and G, region EF had equal
numbers of nonsynonymous and synonymous mutations. Interestingly, antibodies
produced during persistent infection reacted predominantly with the conserved
C-terminus and variable region B. In contrast, infection-induced antibodies
reacted poorly with the N-terminus, variable regions EF and G, and intervening
conserved regions despite the presence of predicted B cell epitopes. Overall,
this study provides an important foundation to define how different segments of
the MgpB adhesin contribute to functionality, variability, and immunogenicity
during persistent M. genitalium infection.