Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium.
BACKGROUND
The continued rise of Clostridium difficile infections worldwide has been accompanied by the rapid emergence of a highly virulent clone designated PCR-ribotype 027. To understand more about the evolution of this virulent clone, we made a three-way genomic and phenotypic comparison of an 'historic' non-epidemic 027 C. difficile (CD196), a recent epidemic and hypervirulent 027 (R20291) and a previously sequenced PCR-ribotype 012 strain (630).


RESULTS
Although the genomes are highly conserved, the 027 genomes have 234 additional genes compared to 630, which may contribute to the distinct phenotypic differences we observe between these strains relating to motility, antibiotic resistance and toxicity. The epidemic 027 strain has five unique genetic regions, absent from both the non-epidemic 027 and strain 630, which include a novel phage island, a two component regulatory system and transcriptional regulators.


CONCLUSIONS
A comparison of a series of 027 isolates showed that some of these genes appeared to have been gained by 027 strains over the past two decades. This study provides genetic markers for the identification of 027 strains and offers a unique opportunity to explain the recent emergence of a hypervirulent bacterium.
London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Richard.Stabler@lshtm.ac.uk
Richard A
RA
Stabler
Miao
M
He
Lisa
L
Dawson
Melissa
M
Martin
Esmeralda
E
Valiente
Craig
C
Corton
Trevor D
TD
Lawley
Mohammed
M
Sebaihia
Michael A
MA
Quail
Graham
G
Rose
Dale N
DN
Gerding
Maryse
M
Gibert
Michel R
MR
Popoff
Julian
J
Parkhill
Gordon
G
Dougan
Brendan W
BW
Wren
D016475:3T3 Cells; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D016466:CHO Cells; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D006224:Cricetinae; D003412:Cricetulus; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010641:Phenotype; D016133:Polymerase Chain Reaction; D021521:Ribotyping; D013045:Species Specificity; D014709:Vero Cells; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile