Evidence that SSR1 can act as a hypermutable contingency gene in Candida albicans : a thesis presented in partial fulfillment of the requirement for the degree of Master of Science in Microbiology at Massey University, Palmerston North, New Zealand
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Date
2010
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Massey University
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Abstract
During adaptation to the host environment, many microorganisms undergo rapid
variation in cell surface phenotype through genetic alteration in hypermutable
contingency genes. One of the main mechanisms underlying these changes is
alteration in the number of DNA repeat units that results in a large and flexible
repertoire of similar but non-identical surface proteins. SSR1, a gene in the
opportunistic pathogen Candida albicans, encodes a repeat-containing cell wall
protein which may play a role in maintaining cell wall strength. This gene contains
2 regions with multiple 6 bp tandem repeat units, encoding the amino acids serine
and alanine, separated by a 200 bp non-repetitive DNA region. This study
investigated whether SSR1 was a hypermutable contingency gene. Among a
worldwide collection of 96 infection-causing C. albicans strains, 24 alleles and 40
allele combinations were identified by fluorescent-based genotyping of SSR1 PCR
products. Sequencing results confirmed that the differences in allele size were
caused by variation in number of tandem repeats. Two very similar allele
combinations were overrepresented (30% and 28%) among a cluster of generalpurpose
genotype (GPG) strains (which is the most widespread cluster) compared
with non-GPG strains (Fisher’s exact test, P=0.0001 and P<0.0001). Among a
worldwide collection of 36 commensal GPG C. albicans strains, 8 allele
combinations were identified by genotyping. One of the two allele combinations
that were overrepresented in GPG infection-causing strains was found significantly
less in GPG commensal strains (Fisher’s exact test, P=0.0004). After culture of C.
albicans cells in vitro for 300 generations, mutation of repeats in SSR1 occurred,
giving a high mutation rate of 1.11×10-4 per cell division. The results indicate that
SSR1 is a hypermutable gene and that it shows clade-specificity with the GPG
cluster. Growth in a rat model did not seem to cause variation in SSR1 and human
host body sites did not seem to be associated with specific SSR1 alleles,
suggesting that SSR1 is not used for short-term adaptation in these environments.
However, the different allele distribution in commensal and infection-causing GPG
strains suggest that SSR1 may have a role in short-term adaptation in GPG
strains, contributing to the change between commensalism and infection. In this
case, SSR1 may act as a hypermutable contingency gene.
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Keywords
Candida albicans, Genetics, SSR1, Hypermutable contingency gene, Microbiology