IRF2 plays an indirect role in inflammasome activation by regulating Caspase-4 and Gasdermin D (GSDMD) levels. However, the in vivo relevance of this regulatory circuit is unknown. We generate IRF2KO ...

Tularemia is a zoonotic disease caused by Francisella tularensis. Most human cases are caused by F. tularensis ssp. tularensis (type A) or F. tularensis ssp. holarctica (type B), with the former consi...

Francisella tularensis is the causative agent of tularemia, a zoonotic disease named after the city of Tulare, California. Symptoms include sudden fever, chills, fatigue, and swollen lymph nodes, among others, and without treatment it is very serious or even fatal. In addition, F. tularensis is considered a potential bioterrorism threat due to its high infectivity and lethality. Ribosomes are key targets for many classes of antibiotics. In this study, we examined the F. tularensis ribosome and determined its structure at 2.5A resolution using cryo-electron microscopy. Notably, we observed the stress-induced ribosome-associated inhibitor A (RaiA) protein bound to the ribosome. RaiA functions as a molecular hibernation factor, inhibiting bacterial translation in response to stress or nutrient deprivation. This mechanism parallels that described in the model organism Escherichia coli and in several pathogenic bacteria, such as Staphylococcus aureus. Furthermore, we solved structures of the antibiotics chloramphenicol and gentamicin bound to the F. tularensis ribosome. Collectively, these results provide structural insights that highlight previously unexplored opportunities for therapeutic intervention.

Francisella tularensis is the causative agent of tularemia, a zoonotic disease named after the city of Tulare, California. Symptoms include sudden fever, chills, fatigue, and swollen lymph nodes, among others, and without treatment it is very serious or even fatal. In addition, F. tularensis is considered a potential bioterrorism threat due to its high infectivity and lethality. Ribosomes are key targets for many classes of antibiotics. In this study, we examined the F. tularensis ribosome and determined its structure at 2.5A resolution using cryo-electron microscopy. Notably, we observed the stress-induced ribosome-associated inhibitor A (RaiA) protein bound to the ribosome. RaiA functions as a molecular hibernation factor, inhibiting bacterial translation in response to stress or nutrient deprivation. This mechanism parallels that described in the model organism Escherichia coli and in several pathogenic bacteria, such as Staphylococcus aureus. Furthermore, we solved structures of the antibiotics chloramphenicol and gentamicin bound to the F. tularensis ribosome. Collectively, these results provide structural insights that highlight previously unexplored opportunities for therapeutic intervention.

Francisella tularensis is a gram negative, facultative intracellular bacterium that causes the zoonotic disease tularemia. F. tularensis is capable of invading mammalian erythrocytes, a phenomenon that enhances colonization of ticks following a blood meal. The colonization of these blood-sucking arthropods presumably enhances transmission to mammalian hosts and increases the persistence of this bacterium within the environment. Therefore, we sought to elucidate host-pathogen interactions...

Francisella tularensis is a gram negative, facultative intracellular bacterium that causes the zoonotic disease tularemia. F. tularensis is capable of invading mammalian erythrocytes, a phenomenon that enhances colonization of ticks following a blood meal. The colonization of these blood-sucking arthropods presumably enhances transmission to mammalian hosts and increases the persistence of this bacterium within the environment. Therefore, we sought to elucidate host-pathogen interactions...

Ticks (Ixodida) are the second most important vectors of infectious diseases in vertebrates, after mosquitoes. They also maintain mutualistic relationships with bacteria, such as endosymbionts that pr...

Abstract. Pulmonary infections often fail to produce long-lived immune memory and the underlying mechanism(s) for this are unclear. Given the complex inter

The illness is caused by the bacteria Francisella tularensis. It's commonly found in small rodents, rabbits, squirrels and beavers. People typically develop the illness from tick and fly bites,…

The emergence of infectious diseases associated with land-use changes is well-documented. However, zoonotic risks originating from European forests, whether from rural development or urban greening, r...