Listeria monocytogenes is a facultative intracellular pathogen that escapes from the vacuole and takes residence in the host cytosol. During infection, the transcription factor PrfA is responsible for recognizing that L. monocytogenes is present in the host cytosol and for activating the suite of virulence factors required for pathogenesis. The cytosolic environmental niche is defined by a unique hybrid aerobic + reduced condition and recent studies suggest that this combination of properties might represent the cue that L. monocytogenes senses to interpret an intracellular localization. To follow up on this finding, a preliminary transposon library screen has been conducted to identify L. monocytogenes genes important for the sensing of reducing properties. From this screen, an 8-gene locus that?s conserved in over 200 gram-positive bacteria was identified. Preliminary experiments demonstrate that these genes encode an abundantly expressed extracellular electron transport chain (EETC) that links extra and intracellular electron pools. Experiments proposed here seek to delineate the role of this novel EETC in L. monocytogenes host sensing and to determine additional functional roles in central metabolism and bacterial competition.
A number of clinically relevant microbial pathogens enter host cells and establish an intracellular habitat where they grow at the direct expense of host. Experiments proposed here seek to address the mechanism by which a model intracellular pathogen, Listeria monocytogenes, uses an extracellular electron transport chain (EETC) to recognize and adapt to the intracellular environment. Findings from the study promise to clarify fundamental features of the cytosolic niche and reveal basic mechanisms of intracellular pathogenesis.
| Light, Samuel H; Su, Lin; Rivera-Lugo, Rafael et al. (2018) A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria. Nature 562:140-144 |
