Rhodococcus equiis a major cause of foal pneumonia and an opportunistic pathogen in immunocompromised humans. While alveolar macrophages constitute the primary replicative niche forR.equi, little is known about how intracellularR. equiis sensed by macrophages. Here, we discovered that in addition to previously characterized pro-inflammatory cytokines (e.g.,Tnfa,Il6,Il1b), macrophages infected withR.equiinduce a robust type I IFN response, includingIfnband interferon-stimulated genes (ISGs), similar to the evolutionarily related pathogen,Mycobacterium tuberculosis. Follow up studies using a combination of mammalian and bacterial genetics demonstrated that induction of this type I IFN expression program is largely dependent on the cGAS/STING/TBK1 axis of the cytosolic DNA sensing pathway, suggesting thatR.equiperturbs the phagosomal membrane and causes DNA release into the cytosol following phagocytosis. Consistent with this, we found that a population of ~12% ofR.equiphagosomes recruits the galectin-3,-8 and -9 danger receptors. Interestingly, neither phagosomal damage nor induction of type I IFN require theR.equi’s virulence-associated plasmid. Importantly,R.equiinfection of both mice and foals stimulates ISG expression, in organs (mice) and circulating monocytes (foals). By demonstrating thatR.equiactivates cytosolic DNA sensing in macrophages and elicits type I IFN responses in animal models, our work provides novel insights into howR.equiengages the innate immune system and furthers our understanding how this zoonotic pathogen causes inflammation and disease.
8 February 2019 in Journal of Applied Microbiology
The use of natural products, such as essential oils (EOs), is a potential novel approach to treat fish bacterial infections with a lower risk of developing resistance. There has been a number of studies reporting the activity of EOs as those obtained from the species Achyrocline satureioides, Aniba parviflora, Aniba rosaeodora, Anthemis nobilis, Conobea scoparioides, Cupressus sempervirens, Illicium verum, Lippia origanoides, and Melaleuca alternifolia against bacteria. However, there are few studies investigating the effect of these EOs against fish bacteria. Therefore, the aim of this study was to evaluate the in vitro antibacterial activity of EOs against the following fish bacteria, Aeromonas hydrophila, Citrobacter freundii, and Raoultella ornithinolytica. Additionally, the in vivo antibacterial activity of the EO L. origanoides was evaluated against experimentally induced A. hydrophila infection of silver catfish (Rhamdia quelen). The EO of L. origanoides was chosen as it showed the highest in vitro antibacterial activity, with minimum inhibitory concentrations ranging from 0.2 to 0.8 mg mL-1. This EO also presented a therapeutic success of 58.33%, on a 30 day A. hydrophila infection. Therefore, we suggested that the EO of L. origanoides may be a viable alternative as a treatment for A. hydrophila infection.