Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing

Abstract

correspondence between case reports and fatality data. These data also establish that mortality rates are not affected by epidemic phase 24. Further confirmation of these results is provided by an analysis of the Aberdeen data (N.B.M-B., P.R. and B.T.G., manuscript in preparation). Concerning infection-induced mortality rates, classic work by Butler 24 , Bartlett 25 , Creighton 5 and others indicates significant mortality due to measles and whooping cough during these periods. Estimates of case fatality rates for measles vary widely, from 1-2% in the postwar era up to 46% prewar 14,26,27 , whereas estimates for whooping cough are in the 3-15% range 24. Data analysis These time series contain a substantial annual component and are further complicated by increasing population sizes over the two periods examined. Hence, analyses of the relationship between measles and whooping cough outbreaks were carried out on de-trended data. We used three separate methods. First, Pearson correlation coefficients were estimated for data aggregated over each epidemic year (October to October). Second, we carried out a linear regression of annual counts of measles against whooping cough and used the slope as a measure of synchrony. The results of this technique were qualitatively identical to those of the Pearson correlation, so we present only those. Finally, we also used Wavelet spectra to explore phase differences between filtered time series 28,29. Further information can be found in the Supplementary Information.

Cytotoxic activity and probable apoptotic effect of Sph2, a sphigomyelinase hemolysin from Leptospira interrogans strain Lai

“…Genomic sequencing and annotation identified 10 genes encoding putative hemolysins in the large circular chromosome (CI, GB: AE010300) of L. interrogans strain Lai (2). All these genes were cloned and expressed in Escherichia coli except LA3540 and LA0177 (3).…”

Pathology and pathophysiology of pulmonary manifestations in leptospirosis

“…Furthermore, in the serovar lai, sequences of genes encoding for proteins that resemble mammalian proteins involved in homeostasis (such as platelet activating factor acetylhydrolase, type A domains of von Willebrand factor, and paraoxanase) have been described. The authors of that study hypothesized that the combination of proteases and the proteins involved in homeostasis could be involved in the genesis of the hemorrhagic lesions [48]. Such genomic studies will certainly enhance our understanding of the molecular mechanisms of leptospiral pathogenesis and contribute to the development of novel vaccines.…”

“…Recently, whole genome sequencing of the Leptospira interrogans serogroup interrogans [47] and lai [48] identified many genes with a potential role in disease pathogenesis. Genes involved in host cell membrane degradation and encoding proteases, which could participate in the mechanisms of endothelial damage, have been sequenced.…”

Avaliação e caracterização de candidatos vacinais voltados para o controle da leptospirose.

“…Os mecanismos envolvidos na patogenicidade das leptospiras não são totalmente conhecidos, mas graças ao sequenciamento do genoma de espécies patogênicas de Leptospira, grandes avanços puderam ser obtidos e sugerem o potencial patogênico apresentado pelas leptospiras (BULACH et al, 2006;CHOU et al, 2012;NASCIMENTO et al, 2004a;NASCIMENTO et al, 2004b;REN et al, 2003 interrogans com laminina, colágeno I, colágeno IV, fibronectina plasmática e celular foi demonstrada pela primeira vez pelo nosso grupo, sugerindo a presença de moléculas adesivas presente em sua superfície. Assim, a primeira proteína de leptospira com capacidade de ligação a laminina foi identificada e nomeada de Lsa24 (BARBOSA et al, 2006).…”

“…Devido à localização, essas proteínas podem participar das interações patógeno-hospedeiro e, ainda, servir de alvo para o sistema imune. Nesse sentido, algumas proteínas de membrana, analisadas por programas de bioinformática têm sido identificadas como possíveis candidatos vacinais em modelo animal (ATZINGEN et al, 2010;ATZINGEN et al, 2012;CULLEN et al, 2002;GAMBERINI et al, 2005;HAAKE et al, 1999;NASCIMENTO et al, 2004a;NASCIMENTO et al, 2004b;PALANIAPPAN et al, 2006;REN et al, 2003;YAN et al, 2009).…”