break out of phagosomal compartments to replicate in the cytosol, F. tularensis strains produce different hemolytic agents, which may facilitate degradation of the phagosome. A hemolysin activity, named NlyA, with immunological reactivity to Escherichia coli anti-HlyA antibody, was identified in biovar F. t. novicida. Acid phosphatase AcpA has been found in other bacteria to act as a hemolysin, whereas in Francisella, its role as a virulence factor is under vigorous debate. F. tularensis contains type VI secretion system (T6SS), also present in some other pathogenic bacteria. It also contains a number of ATP-binding cassette (ABC) proteins that may be linked to the secretion of virulence factors. F. tularensis uses type IV pili to bind to the exterior of a host cell and thus become phagocytosed. Mutant strains lacking pili show severely attenuated pathogenicity. The expression of a 23-kD protein known as IglC is required for F. tularensis phagosomal breakout and intracellular replication; in its absence, mutant F. tularensis cells die and are degraded by the macrophage. This protein is located in a putative pathogenicity island regulated by the transcription factor MglA. F. tularensis, in vitro, downregulates the immune response of infected cells, a tactic used by a significant number of pathogenic organisms to ensure their replication is (albeit briefly) unhindered by the host immune system by blocking the warning signals from the infected cells. This downmodulation of the immune response requires the IglC protein, though again the contributions of IglC and other genes are unclear. Several other putative virulence genes exist, but have yet to be characterized for function in F. tularensis pathogenicity. Genetics Like many other bacteria, F. tularensis undergoes asexual replication. Bacteria divide into two daughter cells, each of which contains identical genetic information. Genetic variation may be introduced by mutation or horizontal gene transfer. The genome of F. t. tularensis strain SCHU4 has been sequenced. The studies resulting from the sequencing suggest a number of gene-coding regions in the F. tularensis genome are disrupted by mutations, thus create blocks in a number of metabolic and synthetic pathways required for survival. This indicates F. tularensis has evolved to depend on the host organism for certain nutrients and other processes ordinarily taken care of by these disrupted genes. The F. tularensis genome contains unusual transposon-like elements resembling counterparts that normally are found in eukaryotic organisms. Phylogenetics Much of the known global genetic diversity of F. t. holarctica is present