The last up-regulated entry is transcriptional regulator, merR family (MAP3267c) which is important
for the response to oxidative stress and antibiotics. Among the down-regulated genes are two sigma factors such as SigI which is activated in response to general stress and SigJ, required for the regulation of expression in stationary phase CYC202 purchase cultures . The susceptibility to lipophilic antibiotics is repressed since four genes coding for transcriptional regulator, tetR family (MAP3052c MAP0155 MAP2262 MAP0335) are down-regulated along with the repression of the glyoxylate path with transcriptional regulator, iclR family (MAP1446c). With respect to the detoxification metabolism during macrophage infection, MAP up-regulates sodC in order to dismutate superoxides, learn more and increases its antibiotic resistance by up-regulating genes such as aminoglycoside phosphotransferase (MAP3197), prolyl 4-hydroxylase, alpha subunit (MAP1976) and antibiotic transport system permease (MAP3532c) for their efflux. Virulence and antigenicity of MAP during infection of THP-1 are dominated by the up-regulation of mpt64, tlyA, peptidase M22 glycoprotease (MAP4261), and family PE-PGRS protein (MAP4144). The
hbha gene for host cell adhesion as well as mce1C for the invasion Compound C ic50 of mammalian host cells are down-regulated, thus limiting the invasive feature of MAP during intramacrophage infection. Lastly, there is a down-regulation of components belonging to antigenic variability such as four PPE family protein (MAP0966c, MAP2927, MAP1515, MAP3737) that are repressed. The stress metabolism shows an up-regulation of acid-resistance membrane protein (MAP1317c) specific for resistance to acidic environment, uspA (MAP1754c) and two entries for the repair of damaged DNA such as recR and end. On the other hand, within this metabolism two entries such as Hsp20 and dnaJ are repressed along with domain-containing protein FAD PitT (MAP2680c, MAP2027c) required for MAP’s survival under nutritional stress. Comparison of
acid-nitrosative multi-stress and THP-1 infection MAP’s transcriptomes MAP’s transcriptome resulting from the acid-nitrosative stress is more complex and rich (n = 988) than the detectable transcriptome during infection of the macrophage line THP-1 (n = 455). Between the two transcriptomes it is possible to find analogies of up-regulation or down-regulation for several entries since 50 and 24 genes are commonly up-regulated and down-regulated, respectively (Figure 3). Homologies can be found in the intermediate metabolism, where there is a repression of the synthesis of glycogen both in the acid- nitrosative stress (glgB glgC) and in the cellular infection (glgC), thus highlighting a limitation in extracellular sources of carbohydrates.