The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.

Mycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are trafficked from the bacterium to the host via unknown mechanisms. Arabinomannan is thought to be a capsular derivative of these molecules, lacking a lipid anchor.

The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.

Mycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important amongst these are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are both trafficked out of the bacterium to the host via unknown mechanisms. An important class of exported LM/LAM is the capsular derivative of these molecules which is devoid of its lipid anchor.

Identification of D-arabinan-degrading enzymes in mycobacteria.

Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the D-arabinan or D-galactan components of arabinogalactan.

Identification of motifs of Burkholderia pseudomallei BimA required for intracellular motility, actin binding, and actin polymerization.

Actin-based motility of the melioidosis pathogen Burkholderia pseudomallei requires BimA (Burkholderia intracellular motility A). The mechanism by which BimA mediates actin assembly at the bacterial pole is ill-defined. Toward an understanding of the regions of B.

Actin-based motility of Burkholderia thailandensis requires a central acidic domain of BimA that recruits and activates the cellular Arp2/3 complex.

Burkholderia species use BimA for intracellular actin-based motility. Uniquely, Burkholderia thailandensis BimA harbors a central and acidic (CA) domain. The CA domain was required for actin-based motility, binding to the cellular Arp2/3 complex, and Arp2/3-dependent polymerization of actin monomers.

Salicylidene acylhydrazide-mediated inhibition of type III secretion system-1 in Salmonella enterica serovar Typhimurium is associated with iron restriction and can be reversed by free iron.

Salmonella enterica serovar Typhimurium is an animal and zoonotic pathogen of worldwide importance. Intestinal colonization, induction of enteritis and systemic translocation by this bacterium requires type III protein secretion. Strategies that target this process have the potential to control infection, pathology and transmission.

Characterization of the effects of salicylidene acylhydrazide compounds on type III secretion in Escherichia coli O157:H7.

Recent work has highlighted a number of compounds that target bacterial virulence by affecting gene regulation. In this work, we show that small-molecule inhibitors affect the expression of the type III secretion system (T3SS) of Escherichia coli O157:H7 in liquid culture and when this bacterium is attached to bovine epithelial cells. Inhibition of T3SS expression resulted in a reduction in the capacity of the bacteria to form attaching and effacing lesions.

Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287/91 provides insights into evolutionary and host adaptation pathways.

We have determined the complete genome sequences of a host-promiscuous Salmonella enterica serovar Enteritidis PT4 isolate P125109 and a chicken-restricted Salmonella enterica serovar Gallinarum isolate 287/91. Genome comparisons between these and other Salmonella isolates indicate that S. Gallinarum 287/91 is a recently evolved descendent of S.

Identification of novel genes and pathways affecting Salmonella type III secretion system 1 using a contact-dependent hemolysis assay.

We screened 5,700 Salmonella enterica serovar Typhimurium mutants for defects in type III secretion system 1 (T3SS-1)-mediated contact-dependent hemolysis to identify novel genes and pathways affecting the activity of T3SS-1. Our data suggest that previously unrecognized factors such as type I fimbriae may modulate the expression, activity, or deployment of this key virulence factor.

Salmonella-induced enteritis: molecular pathogenesis and therapeutic implications.

Salmonella-induced enteritis is a gastrointestinal disease that causes major economic and welfare problems throughout the world. Although the infection is generally self-limiting, subgroups of the population such as immunocompromised individuals, the young and the elderly are susceptible to developing more severe systemic infections. The emergence of widespread antibiotic resistance and the lack of a suitable vaccine against enteritis-causing Salmonella have led to a search for alternative therapeutic strategies.

Inhibition of type III secretion in Salmonella enterica serovar Typhimurium by small-molecule inhibitors.

Type III secretion systems (T3SS) are conserved in many pathogenic gram-negative bacteria. Small molecules that specifically target T3SS in Yersinia and Chlamydia spp. have recently been identified.

The secreted Salmonella dublin phosphoinositide phosphatase, SopB, localizes to PtdIns(3)P-containing endosomes and perturbs normal endosome to lysosome trafficking.

Invasion and survival in mammalian cells by Salmonella enterica is mediated by bacterial proteins that are delivered to the host cell cytoplasm by type III secretion systems. One of these proteins, SopB/SigD, is a phosphoinositide phosphatase that can hydrolyse a number of substrates in vitro including PtdIns(3,5)P2. These substrates are, however, likely to be restricted in vivo by the localization of SopB, as different phosphoinositides have distinct spatial distributions in mammalian cells.

The Salmonella translocated effector SopA is targeted to the mitochondria of infected cells.

This study investigates the Salmonella effector protein SopA. We show that in Salmonella enterica serovar Dublin-infected cells, SopA(1-347) fused to two carboxy-terminal hemagglutinin tags partially colocalized with mitochondria. Transfection of eukaryotic cells with a panel of constructs encoding truncated versions of SopA identified that amino acids 100 to 347 were sufficient to target SopA to the mitochondria.