using the Conserved Domains Database. In addition, for homologues of K+ channel subunits, only hits with regions of sequence similarity that encompassed the selectivity filter sequence of the K+ channel subunit used as bait were acknowledged. Also, where possible, pore homology was confirmed by sequence alignment using ClustalW2.1. Multiple sequence alignments were made using ClustalW2.1 and physiochemical residue colours are shown. Where shown, asterisks below the alignment indicate positions that have a single fully conserved residue, while colons indicate positions that have residues with highly similar properties. For phylogenetic analysis, multiple sequence alignments were made with MUSCLE v3.7 using default parameters. After using GBLOCKS at high stringency to remove regions of low confidence, and removing gaps, Maximum Likelihood analysis was carried out using PhyML v3.0. Phylogenetic trees were depicted using TreeDyn. MUSCLE, 
GBLOCKS, PhyML and TreeDyn were all functions of Phylogeny.fr . All living cells appear to have the physiological ability to synthesize and degrade inorganic polyphosphate molecules. These linear biopolymers comprise chains of phosphate residues linked via `high-energy’ phosphoanhydride bonds, and range from a few to several hundred phosphate residues in length. In bacterial systems, poly-P is involved in a diverse range of biochemical, Salidroside site physicochemical and biological processes; e.g. the modulation of membrane structure and permeability; cell morphogenesis; DNA replication; as well as RNA and protein degradation. Poly-P also acts as an intracellular phosphate store and a biochemical phosphorylation agent. Within pathogenic species of bacteria, polyphosphate has been associated with enhanced levels of virulence, motility, stationary phase survival, persistence, resistance to complement-mediated cell lysis and increased biofilm formation. Bacterial polyphosphate metabolism is also of notable environmental importance, playing a key role in the biological removal of phosphate from wastewater. Consequently, the modulation of intracellular poly-P concentrations is of pivotal importance to numerous physiological processes involved in bacterial growth, viability, adaptability and infection. The metabolism of poly-P in bacteria is mediated by several highly-conserved protein families, including: polyphosphate kinase 1, the main poly-P synthesizing enzyme in most species; polyphosphate kinase 2; polyphosphate/ATP NAD kinase; polyphosphate-AMP phosphotransferase; polyphosphate glucokinase; and exopolyphosphatase, the main hydrolytic enzyme in most species. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22201264 PPX proteins processively cleave phosphate residues from the termini of the polyphosphate chains. In Escherichia coli, the guanosine pentaphosphate 59-phosphohydrolase enzyme also has strong exopolyphosphatase activities. The primary function of this enzyme is to remove the terminal 59-phosphate from guanosine 59-triphosphate, 39-diphosphate, to form guanosine 39,59-bisdiphosphate . Collectively referred to as ppGpp, these two small molecule `alarmones’ are key players in the bacterial stringent response, a coordinated physiological process that enables bacteria to conserve and recycle resources during periods of environmental stress or nutritional deficiency Biochemical Activities of Rv0496 and Rv1026 . In E. coli, it has been demonstrated that pppGpp, and to a lesser extent ppGpp, inhibit the exopolyphosphatase activities of the PPX enzyme, thereby promoting the i
