Citation: Pryjma, M., Apel, D., Parker, C., Huynh, S., Gaynor, E.C. 2012. FdhTU-modulated formate dehydrogenase expression and electron donor availability enhance recovery of Campylobacter jejuni following host cell infection. Journal of Bacteriology. 194:3803-3813. Interpretive Summary: C.jejuni colonizes the mucous layer of the intestine, and the severity of disease by different strains is correlated with host cell interaction and invasion. A microarray-based gene transcription screen to identify genes differentially regulated during C. jejuni interaction with tissue culture cells revealed the up-regulation of a two gene operon fdhT (cjj81176_1492) and fdhU (cjj81176_1493). This operon consists of a putative membrane transporter (fdhT) and a likely DNA binding protein (fdhU). To explore these genes further, targeted non-polar insertional mutants delta fdhT or delta fdhU were generated and tested for their role in intestinal epithelial cell interactions. In contrast, fluorescence microscopy indicated no defects for delta fdhT or delta fdhU mutants in either adherence or invasion. Each mutant was defective for intracellular survival as assessed by colony forming unit enumeration. Orthology suggests that FdhU may act as a regulator, and this operon was already observed to exhibit expression changes during infection. To explore the regulon further, a microarray comparing relative transcription levels in WT, delta fdhU, and complemented background were analyzed. The array revealed a ten-fold induction of the formate dehydrogenase operon in a delta fdhU background suggesting FdhU is a repressor of fdhABC transcription. Analysis of a delta fdhA strain revealed a defect in tissue culture invasion similar to delta fdhU suggesting a link between dis-regulation of the fdhABC operon in a delta fdhU background and a lack of formate dehydrogenase activity. Analysis of bacterial growth in the presence or absence of formate in WT, delta fdhU and delta fdhA backgrounds suggest that both delta fdhU and delta fdhA lack the ability to use formate as an electron donor, further supporting this hypothesis. Previous work has shown that changes in gene regulation occur upon C. jejuni interaction with host cells. Identifying and understanding regulatory units controlling the transition to an infective state will yield a greater understanding of how C. jejuni causes disease.