Ricerc@Sapienza

Efflux pumps are membrane protein complexes conserved in all living organisms. Beyond being involved in antibiotic extrusion in several bacteria, efflux pumps are emerging as relevant players in pathogen-host interactions. We have investigated on the possible role of the efflux pump network in Shigella flexneri, the etiological agent of bacillary dysentery. We have found that S. flexneri has retained 14 of the 20 pumps characterized in Escherichia coli and that their expression is differentially modulated during the intracellular life of Shigella.

Shigella spp. are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation. Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity. Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3. In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum.

The cytosolic appearance and propagation of bacteria cause overwhelming cellular stress responses that induce apoptosis under normal conditions. Therefore, successful bacterial colonization depends on the ability of intracellular pathogens to block apoptosis and to safeguard bacterial replicative niches. Here, we show that the cytosolic Gram-negative bacterium Shigella flexneri stalls apoptosis by inhibiting effector caspase activity. Our data identified lipopolysaccharide (LPS) as a bona fide effector caspase inhibitor that directly binds caspases by involving its O-antigen (O Ag) moiety.

Backgrounds
In several bacterial pathogens, efflux pumps, besides exporting antimicrobial agents, play a role in
bacterial pathogenicity.
Shigella, the causative agent of bacillary dysentery, has conserved 14 out of 20 operons encoding
efflux pumps systems present in the genome of its commensal ancestor Escherichia coli.
Objectives
The aim of this work was (i) to analyze the regulation of Shigella's efflux pumps during the infection of
macrophages and epithelial cells and (ii) to identify and characterize those that are required for

In several bacterial pathogens, efflux pumps, besides exporting antimicrobial agents, play a
role in bacterial pathogenicity.
Shigella, the causative agent of bacillary dysentery, during its evolution towards pathogenicity,
has conserved 14, out of 20 present in the genome of its commensal ancestor Escherichia coli,
operons encoding efflux pumps systems.
The aim of this work is to analyze the induction of efflux pumps conserved in Shigella
during the infection of macrophages and epithelial cells and to identify those that are potentially

Among the intestinal pathogenic Escherichia coli, enteroinvasive E. coli (EIEC) are a group of intracellular pathogens able to enter epithelial cells of colon, multiplicate within them, and move between adjacent cells with a mechanism similar to Shigella, the ethiological agent of bacillary dysentery. Despite EIEC belong to the same pathotype of Shigella, they neither have the full set of traits that define Shigella nor have undergone the extensive gene decay observed in Shigella. Molecular analysis confirms that EIEC are widely distributed among E.

Shigella, the etiological agent of bacillary dysentery (shigellosis), is a highly adapted human pathogen. Itevolved from an innocuous ancestor resembling the Escherichia coli strain by gain and loss of genes andfunctions. While the gain process concerns the acquisition of the genetic determinants of virulence, theloss is related to the adaptation of the genome to the new pathogenic status and occurs by pathoadaptivemutation of antivirulence genes. In this study, we highlight that the SRRz/Rz1lambdoid lysis cassette, eventhough stably adopted in E.