78465771 0.00216317 -2.89367248 0.17 MAP 3522 oxyS Transcriptional regulator, oxyS 4.02084912 0.00065264 2.66363166 0.60 MAP 1643 aceAb Isocitrate lyase 7.02500864 0.00052984 4.30330061

0.07 MAP THP-1 infection transcriptome Gene ID Gene name Gene Product Microarray fold change P-value Real Time-qPCR fold change SD MAP 0654 phoT Phosphate transporter ATP-binding protein VRT752271 mouse -42.44433187 0.02392446 -16.81349291 0.91 MAP 1407 – ADP-ribose pyrophosphatase 69.43061281 0.04255943 27.68837536 0.74 MAP 1317c – Acid-resistance membrane protein 4.39998925 0.00351578 2.90831542 2.42 MAP 1535 pgsA2 CDP-diacylglycerol–glycerol-3-phosphate 3-phosphatidyltransferase 6.40855813 0.00166329 2.51498937 6.99 MAP 2055 – Cystathione beta-lyase -9.04737958 0.00004972 -36.48386353 0.64 Selected MAP genes were validated for their expression profile by Real-Time qPCR to corroborate similar results in microarray data. Three selected genes are shown for the

MAP acid-nitrosative stress transcriptome whereas five genes are shown for MAP THP-1 infection transcriptome. Gene ID: Gene identification code; SD: Standard deviation. Microarray data accession number All transcriptional profile files MK5108 have been submitted to the GEO database at NCBI [NCBI- GEO:GSE32243]. Results Differential transcriptome of MAP under acid-nitrosative multi-stress The whole transcriptome of MAP that has been highlighted during the acid-nitrosative stress (Figure 1) was defined by an up-regulation of 510 genes ( Additional file 1: Table S1) and a down-regulation of 478 genes ( Additional file 1: Table S2) for a total of 988 genes differentially expressed compared to the untreated strain. Transcriptional profile has been grouped into different types of metabolic patterns

according to five functional class: intermediate Ribonucleotide reductase metabolism, energy metabolism, cell wall & membrane, information metabolism and cell processes. Figure 1 Schematic diagram of MAP transcriptional response during acid-nitrosative multistress. Differentially expressed genes during multi-stress were grouped based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) classification and sorted by function. Up arrows indicate an up-regulation of genes to the related metabolism whereas down arrows indicate a down-regulation. Within the intermediate metabolism category, the subgroup of amino acid metabolism is characterized by a significant up-regulation of the anabolic profile of several amino acids, such as branched-chain amino acids with subunits of acetolactate synthase 2 (MAP4208, MAP3000c, MAP0649), and specifically leucine (leuA) as well as an up-regulation of genes involved in the synthesis of aromatic amino acids (aroK) or specifically with entries for the synthesis of tryptophan (trpE, trpB) along with tyrA for the synthesis of tyrosine.