62 plastocyanin – ↓ LIC12829 (LA0790) gltA -1.53 citrate (Si)-synthase – - – carbohydrate transport and metabolism           (G)   -1.82 phosphonomutase – ↓ LIC12331 (LA1416) mgsA -1.72 methylglyoxal synthase – - LIC12733 (LA0909)   -1.58 adolase – ↓ LIC12233 (LA1532)           – amino acid transport and metabolism (E)   -2.17 dioxygenase superfamily protein – - LIC10069 (LA0076) glnK -2.17

nitrogen regulatory protein PII – - LIC10440 (LA3807) csdB -1.60 selenocysteine lyase – - LIC20204 (LB267) speD -1.54 adenosylmethionine decarboxylase – - LIC20239 (LA-SPN3792) gltB -1.53 glutamate synthase (NADH) – - LIC12694 (LA0956)   -1.52 lactoylglutathione or related lyase – - LIC10460 (LA3782)           – nucleotide transport and metabolism (F)   -1.65 purine-nucleoside phosphorylase – - LIC13399 (LA4248) adk -1.55 adenylate kinase – - LIC12852 MI-503 cost (LA0760)           this website – coenzyme transport and metabolism (H) ubiG -1.86 2-polyprenyl-3-methyl-5-     LIC10737 (LA3436)     hydroxy-6-metoxy-1,4- – -       benzoquinol methylase     – lipid transport and metabolism (I) ivd -1.77   – - LIC10363 (LA0414)     isovaleryl-CoA dehydrogenase     – inorganic ion transport and

metabolism amtB -3.10   – - (P) kdpA -2.09 ammonia permease ↑ – LIC10441 (LA3806)     potassium-transporting ATPase A     LIC10990 (LA3112)     chain     aGene ID is based on predicted ORFs of whole-genome sequence of L. interrogans serovar Copenhageni. Gene ID of corresponding serovar Lai is in parenthesis. ORFs of unknown or poorly characterized function were excluded from this table. bPrevious microarray data on the effect of overnight 37°C upshift [11] compared to growth at 30°C. cPrevious microarray data on the effect of osmolarity upshift [13] compared to EMJH medium. d ↑ represents up-regulation of gene expression and ↓ represents down-regulation of gene expression. Information storage and processing Putative transcriptional regulators

including Urocanase a protein in the PadR family (encoded by LIC10378) were up-regulated in response to serum. PadR has been shown to be a transcriptional repressor of padA gene (encoding a phenolic acid decarboxylase) expression in response to phenolic acid stress in Lactobacillus plantarum [46, 47]. However, the target of the leptospiral PadR homolog remains unknown. In the presence of serum, several subunits of 30S and 50S ribosomal proteins of Leptospira were repressed, possibly due to the shift of energy to produce other gene products that are needed for survival in serum. Reduction of ribosomal gene expression has also been found in organisms under various stress conditions such as Streptococcus pneumoniae isolated from infected blood [48], Campylobacter jejuni, Staphylococcus aureus, and Helicobacter pylori in response to acid shock [49–51], and E. coli under anaerobic and acidic conditions [52] and nitrogen and sulfur starvation [53].