NM was also involved in identification of the isolates. VL did the isolations of anaerobic bacteria and BIOLOGTM RXDX-101 assay. YS and DR designed the study and gave important inputs for preparation of manuscript. All authors have read and approved the manuscript.”
“Background In Gram-positive bacteria, proteins released in the extracellular environment are synthesized as precursor polypeptides with a cleavable N-terminal leader peptide as the sole topogenic signal. Precursors are moved across the plasma membrane by a translocon and signal peptidases act on newly translocated precursors to release
the mature polypeptide from the membrane . The events leading to protein translocation across the plasma membrane have been genetically dissected using the model organism Escherichia coli . Most precursor proteins travel in an unfolded state through the SecYEG translocon AZD5363 nmr [2–5], pushed by the cytoplasmic ATPase SecA . Precursor proteins bearing a leader peptide with the twin-arginine motif are moved across the plasma membrane by the Tat translocon [7, 8]. Recently, it has been observed that some bacteria, in particular Firmicutes and Actinobacteria, can secrete proteins lacking a canonical leader peptide . Many of these proteins share some distinguishing and conserved
features that include small size (approximately 100-amino acid residues), a WXG amino acid motif in the middle of the protein  and a conserved three-dimensional structure (helix–turn–helix hairpin) [11, 12]. Together, these proteins form the WXG100 family of proteins . ESAT-6 and CFP-10 of Mycobacterium tuberculosis are the founding members of the WXG100 family of proteins and are identified with the acronym EsxA and EsxB for ESAT-6 extracellular protein A and B. Bioinformatic and genetic approaches have revealed that the esxA and esxB genes cluster with both conserved and non-conserved genes of unknown function that are required for the stability and secretion of WXG100/Esx proteins into
the extracellular milieu [13–16]. These clusters are conserved among several Firmicutes (Figure 1) but not with Mycobacteriaceae who only share EssC-like ATPases [10, 17]. Sirolimus The name ESX has been used to refer to such gene clusters in Mycobacteriaceae and M. tuberculosis for example encodes five ESX clusters (ESX-1 through ESX-5) . In more general term, ESX mediated secretion has been refereed as Type 7 secretion but it was noted that this general designation should not be used for Firmicutes owing to the lack of AZD6244 solubility dmso overall sequence conservation . Clusters bearing esx genes have therefore been referred as ESAT-6 Secretion Systems (ESS) in Staphylococcus aureus and Bacillus anthracis where they have been experimentally examined [16, 19–21] and sometimes as WXG100 Secretion Systems (WSS) .