Specialized secretion systems of pathogenic bacteria commonly transport multiple effectors that act in concert to control and exploit the host cell as a replication-permissive niche. Both the Mycobacterium marinum and the Mycobacterium tuberculosis genomes contain an extended region of difference 1 (extRD1) locus that encodes one such pathway, the early secretory antigenic target 6 (ESAT-6) sys...

In this issue of the Journal of Bacteriology, Chen and colleagues (1) report a novel observation regarding the mycobacterial ESX-1 (ESAT-6 system-1/type VII) protein secretion system. Although the mechanisms underlying their observations are not yet understood, their exciting results unlink the in vitro secretion of the two major ESX-1 substrates, ESAT-6 (EsxA) and CFP-10 (EsxB), from M. tuberc...

We present a summary of our evaluation of VMWare ESX Server 2.5.2. In particular we confirm and work around known timing issues with guest operating systems running on ESX server. Our work validates and adds to the work of other groups modeling the behavior of ESX Server during CPU intensive workloads by exploring in more detail the effects of Hyper-Threading and the overhead of Virtual SMP. We...

VMware ESX enables multiple hosts to share the same physical storage reliably through its highly optimized storage stack and VMware Virtual Machine File System (VMFS). Centralized storage of virtual machines using VMFS provides more control and flexibility. It also enables such unique virtualization capabilities as live migration (VMware VMotion), VMware Distributed Resource Scheduler, VMware H...

After phagocytosis, the intracellular pathogen Mycobacterium tuberculosis arrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set of M. tuberculosis mutants specifically attenuated fo...

The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or negatively, including a key ESX-1 component, the espACD operon. EspR is also thought to be an ESX-1 substrate. Using EspR-specific antibodies in...

The type VII secretion system ESX-5 is a major pathway for export of PE and PPE proteins in pathogenic mycobacteria. These mycobacteria-specific protein families are characterized by conserved N-terminal domains of 100 and 180 amino acids, which contain the proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) motifs after which they are named. Here we investigated secretion of the...

Esat-6 protein secretion systems (ESX or Ess) are required for the virulence of several human pathogens, most notably Mycobacterium tuberculosis and Staphylococcus aureus. These secretion systems are defined by a conserved FtsK/SpoIIIE family ATPase and one or more WXG100 family secreted substrates. Gene clusters coding for ESX systems have been identified amongst many organisms including the h...

The expression of heteroligomeric protein complexes for structural studies often requires a special coexpression strategy. The reason is that the solubility and proper folding of each subunit of the complex requires physical association with other subunits of the complex. The genomes of pathogenic mycobacteria encode many small protein complexes, implicated in bacterial fitness and pathogenicit...

Mycobacterium tuberculosis harbors over 160 genes encoding PE/PPE proteins, several of which have roles in the pathogen's virulence. A number of PE/PPE proteins are secreted via Type VII secretion systems known as the ESX secretion systems. One PE protein, LipY, has a triglyceride lipase domain in addition to its PE domain. LipY can regulate intracellular triglyceride levels and is also exporte...