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Complete genome sequences of important bacterial pathogens and industrial organisms hold significant …

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Genomic insights - lifestyles, adaptations and pathogenic mechanisms
- A Flood of Microbial Genomes–Do We Need More?

Comparative genomics of whole genome sequences of many different pathogenic and commensal forms of microorganisms have improved our perception of the mechanisms of pathogenesis and the transition between pathogenic and non-pathogenic varieties within the same species. It is becoming increasingly evident that distinct genomic differences found in different microbes have a definite impact on pathogenic potential, adaptation to parasitic lifestyles and host/tissue tropism. Some examples in this context are discussed.

In the case where different species of the same genus represent diverse lifestyles it is imperative to have sampled genome sequences from varieties of all forms. For example, the availability of three complete genome sequences from Acinetobacter (i.e. AYE, SDF and A. baylyi ADP1) has enabled comparison in a more general context to tease apart likely genetic changes that enabled adaptation of Acinetobacter species to specific environments [4]. While the three organisms share a large chunk of genes, major differences exist in terms of their flexible genome component such as prophages and insertional sequences [4].

Another interesting lifestyle has been deciphered from the genome sequence of Brachyspira hyodysenteriae [5], an anaerobic intestinal spirochaete that colonizes niches of swine colon and causes dysentery of pigs, a disease of significant economic importance. It appears that the bacterium may have evolved strategies to survive and adapt via gene transfer in the intestinal environment. The genome sequence data suggests presence of genes encoding anaerobic metabolism and mechanisms to cause mucosal damage through the activity of many different virulence factors facilitated by chemotaxis and motility. Interestingly, the chunks of genes believed to have been horizontally acquired by Brachyspira, and that are supposed to have facilitated adaptation and survival of the bacterium within the intestines, belonged mostly to classically ‘enteric type’ of organisms, rather than to other spirochaetal relatives of Brachyspira [5].

Whole genome sequencing and analysis of Mycobacterium indicus pranii (MIP) together with molecular phylogenetic analyses [6] revealed a unique soil and water dwelling lifestyle for this ‘generalist’ organism. MIP had a common ancestor with pathogenic Mycobacterium avium intracellulare complex that did not prefer parasitic adaptation but a free living life-style. Further analysis suggests a shared aquatic phase of MIP with the early pathogenic forms of Mycobacterium, well before the latter diverged to form ‘specialist’ bacterial parasites. This information has an important bearing on our understanding of mycobacterial evolution.

Genomic downsizing and streamlining has been a dominant evolutionary trend in mycobacterial genome evolution that perhaps shapes their host-range and tissue tropism giving rise to ‘specialist’ lineages [6], [7]. Another interesting example of genome optimization through reduction - based - metabolic optimization comes from Yersinia pestis which originated from its closest relative Y. pseudotuberculosis [8]. The same has been true in the case of Brucella ovis whose genome is shorter than the classical zoonotic strains [9] oving to loss of genes via pseudogenization and degradation that has happened concomitant to the narrowing of its host range; it infects only sheep [10]. It has been suggested that inactivation of genes linked to nutrient acquisition and utilization, cell envelope structure and those encoding urease may have played a role in narrowing of the tissue predilection and host range of B. ovis [10]. Another important feature of the B. ovis genome has been the presence of increased number of transposable elements thus hinting towards frequent shuffling (genomic fluidity, or plasticity) of its genome [10].

Variation in gene content, especially the flexible or unstable part of the genome such as mobile elements and genomic islands, has been shown to influence phenotypes such as virulence and antimicrobial resistance. This is especially true for some of the biomedically significant organisms such as the Group A Streptococcus (GAS). Recently, a study analyzing twelve sequenced GAS genomes [11] determined that the resultant ‘metagenome’ holds tremendous potential for understanding pathobiology of the GAS. This multi-genome dataset provides an opportunity to address putative functions, encoded by the exogenous genetic elements, such as antimicrobial resistance. Another major benefit from these genomes includes the ability to develop molecular markers based on GAS mobile elements to tag and track field-level diversity of the circulating strains; this will be of paramount significance in vaccine development and testing.

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