Role of the JAK2/STAT3 pathway on infection of Francisella novicida.

PLoS One

Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.

Published: September 2024

AI Article Synopsis

  • Francisella tularensis causes tularemia, a serious zoonotic disease in humans, largely by growing inside host cells, but the host factors aiding this growth remain largely unidentified.
  • A screening of 368 compounds revealed 56 inhibitors that reduced the infection rate of F. novicida, with a particular focus on cucurbitacin I, which inhibits the JAK2/STAT3 signaling pathway.
  • Both cucurbitacin I and another inhibitor, Stattic, decreased the bacterial load inside host cells but did not impact how the bacteria attach or grow inside, suggesting that the JAK2/STAT3 pathway is crucial for the bacteria's entry into cells, potentially through altering actin dynamics.

Article Abstract

Francisella tularensis is a causative agent of the zoonotic disease tularemia, and is highly pathogenic to humans. The pathogenicity of this bacterium is largely attributed to intracellular growth in host cells. Although several bacterial factors important for the intracellular growth have been elucidated, including the type VI secretion system, the host factors involved in the intracellular growth of F. tularensis are largely unknown. To identify the host factors important for F. tularensis infection, 368 compounds were screened for the negative regulation of F. tularensis subsp. novicida (F. novicida) infection. Consequently, 56 inhibitors were isolated that decreased F. novicida infection. Among those inhibitors, we focused on cucurbitacin I, an inhibitor of the JAK2/ STAT3 pathway. Cucurbitacin I and another JAK2/STAT3 inhibitor, Stattic, decreased the intracellular bacterial number of F. novicida. However, these inhibitors failed to affect the cell attachment or the intrasaccular proliferation of F. novicida. In addition, treatment with these inhibitors destabilized actin filaments. These results suggest that the JAK2/STAT3 pathway plays an important role in internalization of F. novicida into host cells through mechanisms involving actin dynamics, such as phagocytosis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386456PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0310120PLOS

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