The results showed that hemO was up-regulated when leptospires were grown in medium supplemented with Hb. Genes encoding TonB-dependent receptors (LIC12898/LA0706, LIC12374/LA1356, LIC11345/LA2641, selleckchem and LIC10714/LB3468), Fur-like proteins (LIC11006/LA3094, LIC12034/LA1857, LIC11158/LA2887, and LIC20147/LB183), and hemin-binding protein (HbpA encoded by LIC20151/LB191), were not or weakly differentially expressed in response to Hb . Similarly, except for hemO, expression of other genes involved in iron acquisition systems  was not significantly affected by serum in our study. Notably,
one of 12 putative TonB-dependent receptors (LIC11694) , was 1.8-fold up-regulated in response to serum (adjusted P value = 0.02). It is probable that the expression of genes involved in iron uptake and transport depends on check details available iron sources in the environment during
infection. Two genes encoding proteins predicted to be involved in Eltanexor price nitrogen assimilation, amtB (LIC10441), encoding ammonia permease, and glnK (LIC10440), encoding nitrogen regulatory protein II (PII), were down-regulated 3.1-fold (the most strongly down-regulated gene in our study) and 2.17-fold, respectively. In bacteria, glnK and amtB are conserved and co-transcribed as an operon . PII serves as a signal transduction protein for sensing external ammonium availability and nitrogen status of the cell while ammonia permease acts as a channel for ammonium transport . Ammonium is an important source of nitrogen for biosynthesis of amino acids, nucleotides, and biological amines. Expression of the glnKamtB operon is generally induced during growth under
limited ammonium conditions . Therefore, ammonia appears to be available in sufficient concentrations in serum in comparison to EMJH medium, resulting in down-regulation of the glnKamtB operon. Beta-oxidation of CHIR-99021 cost long-chain fatty acids serves as the major mechanism for energy and carbon acquisition by Leptospira [33, 34, 75, 76]. The gene encoding a predicted enoyl-CoA hydratase (LIC12629), which catalyzes the second step of fatty acid oxidation , was up-regulated in response to serum, but the expression of other genes in the fatty acid oxidation pathway was not altered. However, LIC12629 is located distantly from other genes in the same pathway and is clearly regulated independently. Leptospiral genes predicted to be involved in the tricarboxylic acid (TCA) cycle, namely gltA (LIC12829), encoding citrate synthase and sdhA (LIC12002), encoding a flavoprotein subunit of succinate dehydrogenase, and aceF (LIC12476), encoding a subunit of the pyruvate dehydrogenase complex were down-regulated. The results suggest that acetyl-CoA derived from fatty acid oxidation was less likely to feed into the TCA cycle.