Document Detail

Effect of long-term laboratory propagation on Chlamydia trachomatis genome dynamics.
MedLine Citation:
PMID:  23542454     Owner:  NLM     Status:  Publisher    
It is assumed that bacterial strains maintained in the laboratory for long time shape their genome in a different fashion from the nature-circulating strains. Here, we analyzed the impact of long-term in vitro propagation on the genome of the obligate intracellular pathogen Chlamydia trachomatis. We fully-sequenced the genome of a historical prototype strain (L2/434/Bu) and a clinical isolate (E/CS88), before and after one-year of serial in vitro passaging (up to 3500 bacterial generations). We observed a slow adaptation of C. trachomatis to the in vitro environment, which was essentially governed by four mutations for L2/434/Bu and solely one mutation for E/CS88, corresponding to estimated mutation rates from 3.84 x 10(-10) to 1.10 x 10(-9) mutations per base pair per generation. In a speculative basis, the mutations likely conferred selective advantage as: i) mathematical modeling showed that selective advantage is mandatory for frequency increase of a mutated clone; ii) transversions and non-synonymous mutations were overrepresented; iii) two non-synonymous mutations affected the genes CTL0084 and CTL0610, encoding a putative transferase and a transcriptional regulatory protein, respectively, which are families known to be highly prone to undergone laboratory-derived advantageous mutations in other bacteria; and iv) the mutation for E/CS88 is located likely in the regulatory region of a virulence gene (CT115/incD) believed to play a role in subverting the host cell machinery. Nevertheless, we found no significant differences in the growth rate, plasmid load, and attachment/entry rate, between strains before and after their long-term laboratory propagation. Of note, from the mixture of clones in E/CS88 initial population, an inactivating mutation in the virulence gene CT135 evolved to 100% prevalence, unequivocally indicating that this gene is superfluous for C. trachomatis survival in vitro. Globally, C. trachomatis revealed a slow in vitro adaptation that only modestly modifies the in vivo-derived genomic evolutionary landscape.
V Borges; R Ferreira; A Nunes; M Sousa-Uva; M Abreu; M J Borrego; J P Gomes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-28
Journal Detail:
Title:  Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases     Volume:  -     ISSN:  1567-7257     ISO Abbreviation:  Infect. Genet. Evol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-4-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101084138     Medline TA:  Infect Genet Evol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier B.V.
Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 - Lisbon, Portugal.
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