AI Article Synopsis
- Francisella tularensis is a highly dangerous bacterium that causes a lethal disease called tularaemia and can survive in host immune cells by resisting oxidative stress.
- Researchers identified a mutant strain lacking the EmrA1 protein that is more sensitive to oxidative agents and shows reduced ability to grow inside immune cells, which can be fixed by specific interventions.
- The study highlights the role of EmrA1 in protecting F. tularensis against oxidative stress by influencing the secretion of antioxidant enzymes, linking transport functions to the bacterium's defense mechanisms.
Article Abstract
Francisella tularensis is a category A biodefence agent that causes a fatal human disease known as tularaemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defences to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant-sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild-type F. tularensis LVS levels by either transcomplementation, inhibition of ROS generation or infection in NADPH oxidase deficient (gp91Phox(-/-)) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox(-/-) mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defence mechanisms of F. tularensis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097035 | PMC |
| http://dx.doi.org/10.1111/mmi.12509 | DOI Listing |
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