Monitoring the external environment and responding to its changes are essential for the survival of all living organisms. The transmission of extracellular signals in prokaryotes is mediated mainly by twocomponent systems. In addition, genomic analyses have revealed that many bacteria contain eukaryotictype Ser/Thr protein kinases. The human pathogen Streptococcus pneumoniae encodes 13 two-component systems and has a single copy of a eukaryotic-like Ser/Thr protein kinase gene designated stkP. Previous studies demonstrated the pleiotropic role of the transmembrane protein kinase StkP in pneumococcal physiology. StkP regulates virulence, competence, and stress resistance and plays a role in the regulation of gene expression. To determine the intracellular signaling pathways controlled by StkP, we used a proteomic approach for identification of its substrates. We detected six proteins phosphorylated on threonine by StkP continuously during growth. We identified three new substrates of StkP: the Mndependent inorganic pyrophosphatase PpaC, the hypothetical protein spr0334, and the cell division protein DivIVA. Contrary to the results of a previous study, we did not confirm that the ␣-subunit of RNA polymerase is a target of StkP. We showed that StkP activation and substrate recognition depend on the presence of a peptidoglycan-binding domain comprising four extracellular penicillin-binding protein-and Ser/Thr kinase-associated domain (PASTA domain) repeats. We found that StkP is regulated in a growth-dependent manner and likely senses intracellular peptidoglycan subunits present in the cell division septa. In addition, stkP inactivation results in cell division defects. Thus, the data presented here suggest that StkP plays an important role in the regulation of cell division in pneumococcus.Protein phosphorylation is considered the universal language for inter-and intracellular communication in all living organisms. This process, catalyzed by protein kinases, enables translation of extracellular signals into cellular responses and adaptation to a constantly changing environment. Although previous work indicated that histidine kinases of two-component regulatory systems are the most prominent kinases in prokaryotes, recent data provide evidence that eukaryotic-type Ser/Thr protein kinases (ESTPKs) play an important role in prokaryotic cell signaling. The distribution of these enzymes among bacteria is broad but not universal. ESTPKs have been found in nearly two-thirds of the sequenced bacterial strains. Most of these enzymes are encoded by genes in strains belonging to the phyla Proteobacteria (Myxococcales), Actinobacteria, Cyanobacteria, Chloroflexi, Acidobacteria, and Planctomycetes (38). We surveyed sequenced bacterial genomes and found ESTPK-encoding genes also in the bacterial taxa Aquificae,

Nucleoid-associated proteins belong to a group of small but abundant proteins in bacterial cells. These transcription regulators are responsible for many important cellular processes and also are involved in pathogenesis of bacteria. The best-known nucleoid-associated proteins, such as HU, FIS, H-NS, and IHF, are often discussed. The most important findings in research concerning HU protein are described in this mini review. Its roles in DNA compaction, shape modulation, and negative supercoiling induction have been studied intensively. HU protein regulates bacteria survival, growth, SOS response, virulence genes expression, cell division, and many other cell processes. Elucidating the mechanism of HU protein action has been the subject of many research projects. This mini review provides a comprehensive overview of the HU protein.

The nucleoid-associated HU proteins are small abundant DNA-binding proteins in bacterial cell which play an important role in the initiation of DNA replication, cell division, SOS response, control of gene expression and recombination. HU proteins bind to double stranded DNA non-specifically, but they exhibit high affinity to abnormal DNA structures as four-way junctions, gaps or nicks, which are generated during DNA damage. In many pathogens HU proteins regulate expression of genes involved in metabolism and virulence. Here, we show that the Francisella tularensis subsp. holarctica gene locus FTS_0886 codes for functional HU protein which is essential for full Francisella virulence and its resistance to oxidative stress. Further, our results demonstrate that the recombinant FtHU protein binds to double stranded DNA and protects it against free hydroxyl radicals generated via Fenton's reaction. Eventually, using an iTRAQ approach we identified proteins levels of which are affected by the deletion of hupB, among them for example Francisella pathogenicity island (FPI) proteins. The pleiotropic role of HU protein classifies it as a potential target for the development of therapeutics against tularemia.

Francisella tularensis is a highly infectious facultative intracellular bacterium and aetiological agent of tularaemia. The conserved hypothetical lipoprotein with homology to thiol/disulphide oxidoreductase proteins (FtDsbA) is an essential virulence factor in F. tularensis. Its protein sequence has two different domains: the DsbA_Com1_like domain (DSBA), with the highly conserved catalytically active site CXXC and cis-proline residue; and the domain amino-terminal to FKBP-type peptidyl-prolyl isomerases (FKBP_N). To establish the role of both domains in tularaemia infection models, site-directed and deletion mutagenesis affecting the active site (AXXA), the cis-proline (P286T) and the FKBP_N domain (DFKBP_N) were performed. The generated mutations led to high attenuation with the ability to induce full or partial host protective immunity. Recombinant protein analysis revealed that the active site CXXC as well as the cisproline residue and the FKBP_N domain are necessary for correct thiol/disulphide oxidoreductase activity. By contrast, only the DSBA domain (and not the FKBP_N domain) seems to be responsible for the in vitro chaperone activity of the FtDsbA protein.