Imperial College London
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DrJohannaRhodes

Faculty of Medicine, School of Public Health

Honorary Research Fellow
 
 
 
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Contact

 

johanna.rhodes

 
 
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Location

 

Desk 17Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Rhodes:2016:10.1101/083469,
author = {Rhodes, J and Beale, MA and Vanhove, M and Jarvis, JN and Kannambath, S and Simpson, JA and Ryan, A and Meintjes, G and Harrison, TS and Fisher, MC and Bicanic, T},
doi = {10.1101/083469},
title = {A population genomics approach to assessing the genetic basis of within-host microevolution underlying recurrent cryptococcal meningitis infection},
url = {http://dx.doi.org/10.1101/083469},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>Recurrence of meningitis due to<jats:italic>Cryptococcus neoformans</jats:italic>after treatment causes substantial mortality in HIV/AIDS patients across sub-Saharan Africa. In order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing to assess the genetic basis of infection in 17 HIV-infected individuals with recurrent cryptococcal meningitis. Comparisons revealed a clonal relationship for 15 pairs of isolates recovered before and after recurrence showing relapse of the original infection. The two remaining pairs showed high levels of genetic heterogeneity; in one pair we found this to be a result of infection by mixed genotypes, whilst the second was a result of nonsense mutations in the gene encoding the DNA mismatch repair proteins<jats:italic>MSH2, MSH5</jats:italic>and<jats:italic>RAD5</jats:italic>. These nonsense mutations led to a hypermutator state, leading to dramatically elevated rates of synonymous and non-synonymous substitutions. Hypermutator phenotypes owing to nonsense mutations in these genes have not previously been reported in<jats:italic>Cryptococcus neoformans</jats:italic>and represent a novel pathway for rapid within-host adaptation and evolution of resistance to firstline antifungal drugs.</jats:p>
AU  - Rhodes,J
AU  - Beale,MA
AU  - Vanhove,M
AU  - Jarvis,JN
AU  - Kannambath,S
AU  - Simpson,JA
AU  - Ryan,A
AU  - Meintjes,G
AU  - Harrison,TS
AU  - Fisher,MC
AU  - Bicanic,T
DO  - 10.1101/083469
PY  - 2016///
TI  - A population genomics approach to assessing the genetic basis of within-host microevolution underlying recurrent cryptococcal meningitis infection
UR  - http://dx.doi.org/10.1101/083469
ER  -
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