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Nascimento et al. A Summary

Comparative Genomics of Two Leptospira interrogans Serovars Reveals Novel Insights into Physiology and Pathogenesis. Nascimento et al. A Summary. Leptospires. In this paper the sequences of Leptospira interrogans serovar Copenhageni and Leptospira interrogans serovar Lai were compared.

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Nascimento et al. A Summary

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  1. Comparative Genomics of Two LeptospirainterrogansSerovars Reveals Novel Insights into Physiology and Pathogenesis Nascimentoet al. A Summary

  2. Leptospires • In this paper the sequences of LeptospirainterrogansserovarCopenhageni and Leptospirainterrogansserovar Lai were compared. • Serovars are separted by differences in the carbohydrate componatns of the surface polysaccarides. • Many Serovars infect mammalian hosts, and leptospirosis is considered the most widespread zoonotic disease, meaning it can be spread from humans to animals and vise versa.

  3. Genome Features • There is 95% identity between the nucleotides of the two genomes. • The average percent identity of the nucleotides between pairs of predicted protein coding genes that are orthologs is 99%. • There is a large inversion on Chromosome I (CI), which most likely took place in serovar Lai. • The rRNA genes in L. interrogansare not organized together like in other bacteria, but are spread throughout CI. • Many of the genes unique to Lai are located in one 54-kb region not found Copenhageni.

  4. Energy Metabolism • The major energy and carbon source of Leptospira species is the beta-oxidation of long-chain fatty acids. A complete beta-oxidation route was found • Under normal laboratory conditions L. interroganscannot utilize glucose, however the glucose utilization pathway is complete. • Glucose may not be utilized because of a limited uptake system. • The bacteria are aerobes, and electron transport chain components are present

  5. Transport • 40-60% of proteins with four or more transmembrane segments in the fully sequenced prokaryotes are related to transport • 111 proteins were found having four or more transmembrane segments for which no specific function could be found. (could be transport proteins)

  6. DNA Repair • Leptospiers are exposed to UV light during the free living stage of their life cycles so they are equipped with proteins which correct UV damage to DNA. • However, the normal proteins responsible for oxidative base damage are not found in L. interrogans. They do have Exonuclease III orthologs, ExoA, and Nth which may help repair this damage.

  7. Oxidative Stress • Oxidative stress is the imbalance between production of reactive oxygen and the ability of the organism to detoxify or repair damage damage caused by the reactive oxygen. • Superoxide dismutase, which protects against antioxidant damage, is absent in Lai and Copenhageni. • Two regulons (SoxRS and OxyR) which also protect against oxidative stress are also missing. • Lai and Copenhageni may have a yet unknown way of coping with oxidative stress.

  8. Regulatory Functions • Leptospirers must be able to respond to outside stimuli • 79 genes were found that code for signal transduction mechanisms. • Also, cyclic nucleotides, which act as second messengers, also have a major regulatory role in Leptospirers. • Copies of genes encoding BolA-like proteins, which are part of a stress response system, were identifies in L. interrogansbut not in two other spirochetes.

  9. Pathogenicity • Many genes were identified which have a potential role in pathogenesis including: • 79 genes for motility and chemotaxis necessary for penetrating host tissue barriers during infection. • Over 200 genes needed to adhere to host tissue. • 8 genes for host cell membrane degradation • 3 genes coding for proteases

  10. Surface Lipopolysaccharides • Lipopolysaccharides distinguish the leptospiral surface from other invasive spirochetes. • LPSs play a major role in pathogenesis. 23 LPS genes were indentified • Flexibility in the pathways that make LPSs allows Leptospires to to adapt to new host species. • Lai and Copenhageni have very similar polysaccharide synthesis proteins, however proteins involved in the synthesis of the LPS O sidechain are different. • This may be contribute to their serovar differences and reflects evolutionary adaptation to different animal hosts.

  11. Insertion Sequences (ISs) • ISs generate genetic diversity in prokaryotic genomes through prolifertionand by moving from one insertion site to another. • Four previously described ISs elements were found in Lai and Copenhageni as well as one new LSs element, ISlin1. • ISlin1 is the most polymorphic between the two genomes, which suggests that activity of this transposable factor occurred after serovar separation and was caused by different environmental stress factors. • By analyzing patterns of IS amplifications in each genome it is possible to map old insertions common to both serovars.

  12. Vaccine Development • Current vaccines do not induce long-term protection against Leptospirer infection. This is because there are so many different pathogenic serovars, and and it is expensive to produce multi-serovar vaccines. • Targeting outer membrane proteins that are the same in many serovars in a recombinant vaccine may provide an answer to this problem.

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