Thursday, August 19, 2010

Faculty of 1000’s most viewed top 10 evaluations: Evaluation of Aziz and Nizet, Sci Transl Med 2010 Jan 27 2(16):16ps4

Pathogen Micro-evolution in High Resolution (see the evaluation at F1000)

This perspective by Aziz and Nizet stresses that key hypotheses regarding microbial strain evolution or virulence cannot be addressed through conventional genotyping methods that often do not offer enough resolution of minor changes between closely related strains, such as insertion, deletion and substitution polymorphisms. Just like siblings and identical twins having their own personalities and phenotypes due to genetic, epigenetic or environmental confounders, paired/clonal isolates of bacteria, even if genetically identical, have their own colonization traits and pathogenic potentials due to their 'variome'.

Previously, people used to 'characterize' and individualize strains and isolates of bacterial pathogens by means of genetic fingerprinting or DNA profiling. However, recent revelations based on whole genome sequencing have showed that any two strains, even if (seemingly clonal) could be dramatically different in their functional capabilities, owing mainly to the single nucleotide polymorphisms (SNPs). This article, thus, potentially brings about the importance of a 'variome' in understanding evolution of pathogens, rather than putting emphasis on the core genome. In our own experience, Helicobacter pylori serially isolated from a single patient over a decade were different in containing or losing as much as ~51 open reading frames (ORFs) when whole genomes were sequenced (N Ahmed, T Taylor, F Megraud, unpublished data). These isolates were previously shown to belong to only one parental strain and were clonal according to the randomly amplified polymorphic DNA (RAPD), and MLST based genotyping {1}. As suggested in this paper, genome-wide analyses of SNPs between paired strains isolated from the same patient, or between input vs. output strains generated in a suitable animal model, could reveal important genetic 'switch' mechanisms critical for survival, adaptation and invasion potentials of the bacterial pathogens.

References: {1} Prouzet-Mauléon et al. J Clin Microbiol 2005, 43:4237-41 [PMID:16081988].

Evaluated 10 Aug 2010

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