The and Genes Conserved among Tetrapyrrole Synthesizing-Deficient Are Involved in Bacteroides fragilis Heme Assimilation and Survival in Experimental Intra-abdominal Infection and Intestinal Colonization.

The human intestinal anaerobic commensal and opportunistic pathogen does not synthesize the tetrapyrrole protoporphyrin IX in order to form heme that is required for growth stimulation and survival Consequently, acquires essential heme from host tissues during extraintestinal infection. The absence of several genes necessary for heme biosynthesis is a common characteristic of many anaerobic bacteria; however, the gene, encoding a uroporphyrinogen III synthase for an early step of heme biosynthesis, is conserved among the heme-requiring that inhabit the mammalian gastrointestinal tract. In this study, we show that the ability of to utilize heme or protoporphyrin IX for growth was greatly reduced in a Δ mutant. This growth defect appears to be linked to the suppression of reverse chelatase and ferrochelatase activities in the absence of In addition, this Δ suppressive effect was enhanced by the deletion of the gene, which encodes an Mg-chelatase protein belonging to the TPases ssociated with various cellular ctivities (AAA) superfamily of proteins. Furthermore, the Δ mutant and the Δ Δ double mutant had a severe survival defect compared to the parent strain in competitive infection assays using animal models of intra-abdominal infection and intestinal colonization. This shows that the presence of the and genes in seems to be linked to pathophysiological and nutritional competitive fitness for survival in host tissues. Genetic complementation studies and enzyme kinetics assays indicate that UroS is functionally different from canonical bacterial UroS proteins. Taken together, these findings show that heme assimilation and metabolism in the anaerobe have diverged from those of aerobic and facultative anaerobic pathogenic bacteria.