The effect of environmental conditions on expression of Bacteroides fragilis and Bacteroides thetaiotaomicron C10 protease genes

Abstract

BackgroundBacteroides fragilis and Bacteroides thetaiotaomicron are members of the normal human intestinal microbiota. However, both organisms are capable of causing opportunistic infections, during which the environmental conditions to which the bacteria are exposed change dramatically. To further explore their potential for contributing to infection, we have characterized the expression in B. thetaiotaomicron of four homologues of the gene encoding the C10 cysteine protease SpeB, a potent extracellular virulence factor produced by Streptococcus pyogenes.ResultsWe identified a paralogous set of genes (btp genes) in the B. thetaiotaomicron genome, that were related to C10 protease genes we recently identified in B. fragilis. Similar to C10 proteases found in B. fragilis, three of the B. thetaiotaomicron homologues were transcriptionally coupled to genes encoding small proteins that are similar in structural architecture to Staphostatins, protease inhibitors associated with Staphopains in Staphylococcus aureus. The expression of genes for these C10 proteases in both B. fragilis and B. thetaiotaomicron was found to be regulated by environmental stimuli, in particular by exposure to oxygen, which may be important for their contribution to the development of opportunistic infections.ConclusionsGenes encoding C10 proteases are increasingly identified in operons which also contain genes encoding proteins homologous to protease inhibitors. The Bacteroides C10 protease gene expression levels are responsive to different environmental stimuli suggesting they may have distinct roles in the bacterial-host interaction.

Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice

“…25 We also observed a potential regulatory arrangement between peptidase and inhibitor similar to that described in Bacteroides fragilis where the gene pair is cotranscribed and responsive to environmental stimuli, particularly oxygen. 26 Increased oxygen availability associated with epithelial damage induced by transplant conditioning may therefore provide stimulus for peptidase expression while also promoting expansion of facultative anaerobes such as E. coli. 36 The bloom of E. coli we observed associated with the development of acute GVHD is consistent with previous observations both in mice and humans.…”

“…25 Within GVHD19, several C10 peptidases are encoded directly adjacent to a putative serine protease inhibitor (serpin) that may act as a regulator of peptidase expression. 26 GVHD19 also encodes two-class C25 peptidases, of which gingipain produced by Porphyromonas gingivalis is the reference enzyme, and both GVHD19 and GVHD29 encode M6 peptidases, metalloendopeptidases shown to be important in degrading immune system elements. 25 Other proteins of interest present in the enriched genomes include homologs of potential adhesins such as the leucine-rich repeat encoding internalin J, most closely resembling that of Porphyromonas spp.…”

Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS

“…This supports a predominantly inhibitory role of microbiota on PA,13 which could be due to secretion of protease inhibitors like elafin,50 siropins,51 alpha-2 macroglobulin52 and miropins 53. However, microbial production of proteases is also possible,5 54 55 which in some cases like Enterococcus faecalis produced gelatinase, can disrupt barrier function 4. Recently, non-ribosomal gene clusters, present in 88% of samples from the human microbiome project, were found to secrete small molecules with protease inhibitory properties 56.…”

An altered gut microbiota in duck-origin parvovirus infection on cherry valley ducklings is associated with mucosal barrier dysfunction

“…The variety existence of potential immune evasion peptidases within members of “ S24-7 ” does not rule out a typically commensal relationship with the host. However, they may provide the ability to opportunistic infection under the appropriate conditions ( Thornton et al., 2012 ). Furthermore, Unclassified_S24-7 , a gram-negative bacterium, increased the plasma LPS–indicated translocation of bacterium, promoting the inflammatory response and inducing the immune disorder ( Dillon et al., 2014 ).…”