Microbiology Select

Microbial pathogens have evolved strategies to live and multiply within their hosts, who in turn have evolved surveillance systems that detect such pathogens and trigger countermeasures. This Microbiology Select highlights recent papers that reveal new aspects of these host and microbial strategies. The bacterial pathogen that causes typhoid fever in humans, Salmonella enterica serovar Typhi (S. Typhi), can colonize its human hosts for their entire lifetime. S. Typhi secretes a toxin whose active component is a protein with DNase activity, CdtB. Intoxicated host cells exhibit cell-cycle arrest resulting from DNA damage. Spanò et al. (2008) now show that S. Typhi CdtB is part of a multifunctional toxin with a complex evolutionary ancestry, which the authors have named ''typhoid toxin.'' In addition to CdtB, typhoid toxin is composed of subunits PltA and PltB, which are homologs of the ADP ribosylating A subunit of pertussis toxin and one of the components of its B subunit, respectively. The S. Typhi multipartite toxin is produced only when the bacterium is within a host cell, but Spanò et al. show that this toxin does not directly intoxicate this host cell. Instead, like a hormone, the toxin acts after it has been secreted and then taken up, either by the infected toxin-producing cell itself or by distant uninfected cells. Indeed, addition of a toxin-neutralizing antibody eliminated the toxicity in infected and unin-fected cells. The authors hypothesize that infected cells lacking a receptor for the exported toxin could act as toxin delivery factories. The next step will be to identify the role of typhoid toxin during persistent infection, which may confirm that this unusual mode of exotoxin delivery is key for S. Typhi's adaptation to life within a human host. Listeria monocytogenes is a bacterial pathogen that causes opportunistic infections in humans and, like other pathogens, secretes a toxin as part of its intracellular lifestyle. L. monocytogenes secretes listeriolysin O (LLO), a cholesterol-dependent pore-forming toxin. After entering phagocytic cells, L. monocytogenes occupies a vacuole, whereupon LLO perforates the vacuolar membrane, blocking maturation of the vac-uole into an antibacterial environment and facilitating escape of bacteria to the hospitable cytosol. Cytosolic bacteria rapidly multiply, ultimately infecting neighboring cells. Now, Birmingham et al. (2008) reveal yet another way in which LLO subverts host cell defenses. They show that a subpopulation of intracellular L. monocytogenes does not escape to the cytosol but can be found slowly replicating within large non-degradative vacuoles. …