Subversion of Host Recognition and Defense Systems by Francisella spp

Abstract

SUMMARY Francisella tularensis is a Gram-negative intracellular pathogen and the causative agent of the disease tularemia. Inhalation of as few as 10 bacteria is sufficient to cause severe disease, making F. tularensis one of the most highly virulent bacterial pathogens. The initial stage of infection is characterized by the “silent” replication of bacteria in the absence of a significant inflammatory response. Francisella achieves this difficult task using several strategies: (i) strong integrity of the bacterial surface to resist host killing mechanisms and the release of inflammatory bacterial components (pathogen-associated molecular patterns [PAMPs]), (ii) modification of PAMPs to prevent activation of inflammatory pathways, and (iii) active modulation of the host response by escaping the phagosome and directly suppressing inflammatory pathways. We review the specific mechanisms by which Francisella achieves these goals to subvert host defenses and promote pathogenesis, highlighting as-yet-unanswered questions and important areas for future study.

Complement sensitivity and factor H binding of European Francisella tularensis ssp. holarctica strains in selected animal species

“…holarctica strains showed differences in the resistance of the strains to serum killing and among the hosts' susceptibility (Fig. 1), in conformity with previous observations (Jones et al, 2012). In tularaemia and intracellular bacteria research, a frequently used experimental infection model is the mouse infected with F. tularensis ssp.…”

“…holarctica strain LVS has been described in humans (Nasr and Klimpel, 2008). However, the exact mechanism of this binding has not been discovered yet, but fibrinogen and/or plasmin are hypothesised to have a promoter role in fH binding to F. tularensis cell surface (Crane et al, 2009;Jones et al, 2012). Although in the present study host-pathogen interactions were observed by complement sensitivity assays, further examinations on fH binding to bacterial cell membrane proteins using Western blot assays did not reveal specific interactions in any of the animal species examined (Fig.…”

“…Even the attenuated live vaccine strain of F. tularensis ssp. holarctica (LVS) can produce lethal infection in mouse (Jones et al, 2012). The European brown hare (Lepus europaeus) is considered to be moderately sensitive to tularaemia.…”

“…For the successful invasion of the host system F. tularensis developed many mechanisms to evade extracellular and intracellular immune responses (Zarrella et al, 2011;Jones et al, 2012). The complement system is a major extracellular defence, part of the innate immune system, and it is activated by three pathways (classical, mannan-binding lectin and alternative pathways).…”

A CRISPR-Cas system enhances envelope integrity mediating antibiotic resistance and inflammasome evasion

“…novicida is capable of causing disease in a number of mammalian species, including humans (12)(13)(14). During infection, F. novicida must resist the action of numerous antimicrobials that are present on mucosal surfaces and within phagosomes of innate immune cells such as macrophages (15). Compared with…”