Frequent homologous recombination events in Mycobacterium tuberculosis PE/PPE multigene families: potential role in antigenic variability.

Anis Karboul 1 Alberto Mazza 2 Nicolaas C Gey van Pittius 3 John L Ho 4 Roland Brousseau 2 Helmi Mardassi 1, *
* Corresponding author
1 Institut Pasteur de Tunis
2 Biotechnology Research Institute of Montreal
3 Department of Biomedical Sciences, Faculty of Health Sciences
4 Division of International Medicine and Infectious Diseases
Abstract : The PE and PPE (PE/PPE) multigene families of Mycobacterium tuberculosis are particularly GC-rich and share extensive homologous repetitive sequences. We hypothesized that they may undergo homologous recombination events, a mechanism rarely described in the natural evolution of mycobacteria. To test our hypothesis, we developed a specific oligonucleotide-based microarray targeting nearly all of the PE/PPE genes, aimed at detecting signals for homologous recombination. Such a microarray has never before been reported due to the multiplicity and highly repetitive and homologous nature of these sequences. Application of the microarray to a collection of M. tuberculosis clinical isolates (n = 33) representing prevalent spoligotype strain families in Tunisia allowed successful detection of six deleted genomic regions involving a total of two PE and seven PPE genes. Some of these deleted genes are known to be immunodominant or involved in virulence. The four precisely determined deletions were flanked by 400- to 500-bp stretches of nearly identical sequences lying mainly at the conserved N-terminal region of the PE/PPE genes. These highly homologous sequences thus serve as substrates to mediate both intergenic and intragenic homologous recombination events, indicating an important function in generating strain variation. Importantly, all recombination events yielded a new in-frame fusion chimeric gene. Hence, homologous recombination within and between PE/PPE genes likely increased their antigenic variability, which may have profound implications in pathogenicity and/or host adaptation. The finding of high prevalence (approximately 45% and approximately 58%) for at least two of the genomic deletions suggests that they likely confer advantageous biological attributes.
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Submitted on : Thursday, October 10, 2013 - 1:04:55 PM
Last modification on : Thursday, February 7, 2019 - 3:51:01 PM

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Anis Karboul, Alberto Mazza, Nicolaas C Gey van Pittius, John L Ho, Roland Brousseau, et al.. Frequent homologous recombination events in Mycobacterium tuberculosis PE/PPE multigene families: potential role in antigenic variability.. Journal of Bacteriology, American Society for Microbiology, 2008, 190 (23), pp.7838-46. ⟨10.1128/JB.00827-08⟩. ⟨pasteur-00871758⟩

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