The percentage of differentially regulated genes was calculated by dividing number of genes up- and down-regulated in each category by the total number of up- and down-regulated genes, respectively × 100. The COG functional categories are as follows: information storage and processing (includes J, translation; A, RNA processing and modification; K, transcription; L, replication, Selleckchem SAHA recombination, and repair; B, chromatin structure and dynamics); cellular processes and

signaling (includes D, cell cycle control, cell division, chromosome partitioning; MLN4924 in vitro Y, Nuclear structure; V, defense mechanisms; T, signal transduction mechanisms; M, cell wall, membrane, or envelope biogenesis; N, cell motility;

Z, cytoskeleton; W, extracellular structures; U, intracellular trafficking, secretion, and vesicular trans- port; O, posttranslational modification, protein turnover, chaperones); metabolism (includes C, energy production and conversion; G, carbohydrate transport and metabolism; Savolitinib E, amino acid transport and metabolism; F, nucleotide transport and metabolism; H, coenzyme transport and metabolism; I, lipid transport and metabolism; P, inorganic ion transport and metabolism; Q, secondary metabolite biosynthesis, transport, and catabolism); poorly characterized (includes R, general function prediction only; S, function unknown; and -, not in COGs). The most highly up-regulated gene (11.5-fold) Avelestat (AZD9668) was LIC13291, encoding a putative ankyrin repeat protein [Additional file 1]. Ankyrin repeat-containing proteins are ubiquitous proteins that play a role in protein-protein interactions [42–44]. LIC13291 is one of 12 predicted proteins with ankyrin

repeat domains in L. interrogans [34]. However, protein interactions and partners of ankyrin repeat proteins in L. interrogans have not yet been characterized. It is possible that up-regulation of this gene may be crucial for interactions of proteins involved in several functions such as intracellular signaling, nutrient acquisition, and transcriptional regulation to promote survival of Leptospira in response to stress conditions encountered in serum. Interestingly, 11 of 55 (20%) genes that were shown to be up-regulated in our study are unique to L. interrogans and are not present in the genome of the saprophytic L biflexa [45] [Additional file 1] which is susceptible to complement killing. These up-regulated unique L. interrogans genes may encode unique leptospiral virulence factors but their role, if any, in pathogenesis has yet to be determined. The complete lists of significantly up- and down-regulated genes are shown as [Additional files 1 and 2] respectively. Differentially regulated genes of known or predicted function in each broad COG category (Tables 2 and 3) are discussed below.