coli strains in the acidic stomach and host intestinal environment, and neutralize intracellular acidic fermentation products [41, 42]. Strong abundance changes of several SD1 enzymes contributing to pH homeostasis in this pathogen were identified in a recent study (15). This data lends further credence to the important function of two acid resistance (AR) systems, AdiA/AdiC and GadB/GadC, to maintain the intracellular pH in SD1 cells during gastric passage and, possibly, as a result of increased generation of acidic

CHIR98014 cost fermentation products in the intestine. The orthologous AR systems were previously characterized in E. coli [42]. While increases of AdiA were strong in vivo, they also revealed variability comparing the piglet-derived samples (Additional File 3, Table S3). Of the transcription factors GadX, EvgA and YdeO, all reported to influence expression of acid resistance genes [42, 43], EvgA was increased in vivo suggesting a key regulatory role of EvgA during acidic

stress in SD1. As also reported earlier (15), two periplasmic acid resistance chaperones (HdeA, HdeB) which protect periplasmic proteins from aggregation and denaturation at low pH were increased VEGFR inhibitor in SD1 cells in vivo. Hde proteins expose hydrophobic protein surfaces at low pH and initiate formation of aggregates with denatured periplasmic protein substrates [44, 45]. Host invasion by SD1 implicates the invasion and release from gut epithelial cells and cells of the innate and adaptive immune systems. SD1 cells are exposed to toxic molecules produced and secreted by cells of the immune system. We mined proteomic data for indicators of the molecular response to toxins. The most intriguing finding

was the high abundance of nitric oxide (NO) dioxygenase (HmpA) detected only under in vivo conditions. NO is known to be produced in large quantities in macrophages and is toxic to intracellular bacteria. In M. tuberculosis, the nitric oxide dioxygenase HbN was shown to be important for nitrite detoxification Fenbendazole [46]. A hydroxylamine reductase, YbjW, also scavenges toxic by-products of nitrogen metabolism and was detected only in vivo in SD1 cells. We speculate that the expression of these SD1 enzymes reflected memory of a previous intracellular life stage. Both enzymes are interesting targets for inhibitory drug design. To cope with oxidative stress, SD1 cells displayed increased SAHA HDAC manufacturer abundances of superoxide dismutases (SOD) whose expression has been linked to oxygen availability in E. coli in vivo [47]. The previously mentioned regulator FNR and FNR-dependent small RNAs appear to be implicated in oxygen-dependent SOD abundance changes [48]. SodA and SodC were decreased in vivo, while iron-dependent SodB was clearly increased in vivo. An increase was noticed as well for the alkyl hydroperoxide reductase subunits AhpF/AhpC in vivo. The AhpC/AhpF subunits have also been implicated in the S.