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Certain microbial pathogens exploit cellular actin polymerization to disseminate through tissue. Polymerization of actin propels Shigella flexneri to the cell periphery in an N-WASP- and Arp2/3-dependent fashion, whereupon the bacteria spread into adjacent cells via plasma membrane protrusions. Heindl et al. (p. 193-203) demonstrate that efficient formation of plasma membrane protrusions by Shigella depends on a distinct cellular pathway of actin polymerization that involves the diaphanous formins. Expression of a dominant interfering construct or knockdown of formin mRNA levels inhibited protrusion formation and bacterial spread. Thus, Shigella usurps two distinct actin polymerization machines during spread.
Due to their activity as both signaling molecules and potentially harmful components, reactive oxygen species (ROS) may participate in the early host response to infection in epithelial cells. Boncompain et al. (p. 80-87) show that infection by the strict intracellular pathogen Chlamydia trachomatis induces the production of ROS. However, ROS production is only transient, and the activity of the NADPH oxidase is eventually shut down. This study supports the hypothesis that ROS production is one of the early lines of defense used by epithelial cells against bacterial invasion, a defense circumvented by Chlamydia.
Francisella tularensis is a facultative intracellular bacterium that causes acute, lethal disease. Virulence of this pathogen is associated with its ability to evade initiation of inflammatory responses. In this issue, Chase and Bosio (p. 154-167) demonstrate that the absence of the host receptor CD14 on key target cells, such as dendritic cells, contributes to the ability of F. tularensis to evade detection by host cells in vitro and in vivo. Supplementation of CD14 to either dendritic cells or lung cells restored the ability of host cells to produce inflammatory cytokines following infection with F. tularensis and contributed to early control of bacterial replication.
Acid phosphatases have been associated with pathogenesis of various intracellular microbial pathogens, including phagosomal escape of the cytosolic bacterium Francisella novicida. Using genomic comparisons and gene deletions in the highly virulent type A F. tularensis subspecies, Child et al. (p. 59-67) show that most acid phosphatase-encoding genes present in F. novicida are disrupted in virulent F. tularensis subspecies via chromosomal rearrangements. Furthermore, the conserved genes in type A strains are dispensable for phagosomal escape and virulence. These findings suggest functional differences between Francisella species and illustrate that loss of function through genomic decay is associated with high levels of virulence of a bacterial pathogen.
Despite advances in the genetic analysis of Borrelia burgdorferi, we understand little about how transcriptional regulators alter its gene expression. Hyde et al. (p. 265-274) link bosR to an inducible promoter and show that induction of bosR (and concomitant production of BosR) is required for maximal growth, resistance to H2O2, and induction of genes required for oxidative detoxification. This work illustrates that BosR is required for the borrelial oxidative stress response. The induction of bosR also stimulates the production of known virulence determinants, suggesting that BosR interfaces with borrelial pathogenic pathways.