Subversion of host recognition and defense systems by Francisella spp.
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.
Department of Microbiology and Immunology, Microbiology and Molecular Genetics Program, Emory University, Atlanta, Georgia, USA.
Crystal L
CL
Jones
Brooke A
BA
Napier
Timothy R
TR
Sampson
Anna C
AC
Llewellyn
Max R
MR
Schroeder
David S
DS
Weiss
D000818:Animals; D005604:Francisella tularensis / Q000254:growth & development / Q000472:pathogenicity*; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050296:Microbial Viability; D010588:Phagosomes / Q000382:microbiology; D014406:Tularemia / Q000382:microbiology*
D018836:Inflammation Mediators