English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

For pathogenic bacteria, host-derived heme represents an important metabolic cofactor and a source for iron. However, high levels of heme are toxic to bacteria. We have previously shown that excess heme has a growth-inhibitory effect on the Gram-positive foodborne pathogen  Listeria monocytogenes , and we have learned that the LhrC1-5 family of small RNAs, together with the two-component system (TCS) LisRK, play a role in the adaptation of  L. monocytogenes  to heme stress conditions. However, a broader knowledge on how this pathogen responds to heme toxicity is still lacking. Here, we analyzed the global transcriptomic response of  L. monocytogenes  to heme stress. We found that the response of  L. monocytogenes  to excess heme is multifaceted, involving various strategies acting to minimize the toxic effects of heme. For example, heme exposure triggers the SOS response that deals with DNA damage. In parallel,  L. monocytogenes  shuts down the transcription of genes involved in heme/iron uptake and utilization. Furthermore, heme stress resulted in a massive increase in the transcription of a putative heme detoxification system,  hrtAB , which is highly conserved in Gram-positive bacteria. As expected, we found that the TCS HssRS is required for heme-mediated induction of  hrtAB  and that a functional heme efflux system is essential for  L. monocytogenes  to resist heme toxicity. Curiously, the most highly up-regulated gene upon heme stress was  lmo1634 , encoding the  Listeria  adhesion protein, LAP, which acts to promote the translocation of  L. monocytogenes  across the intestinal barrier. Additionally, LAP is predicted to act as a bifunctional acetaldehyde-CoA/alcohol dehydrogenase. Surprisingly, a mutant lacking  lmo1634  grows well under heme stress conditions, showing that LAP is not required for  L. monocytogenes  to resist heme toxicity. Likewise, a functional ResDE TCS, which contributes to heme-mediated expression of  lmo1634 , is not required for the adaptation of  L. monocytogenes  to heme stress conditions. Collectively, this study provides novel insights into the strategies employed by  L. monocytogenes  to resist heme toxicity. Our findings indicate that  L. monocytogenes  is using heme as a host-derived signaling molecule to control the expression of its virulence genes, as exemplified by  lmo1634 .

frontiers in microbiology

Listeria monocytogenes Relies on the Heme-Regulated Transporter hrtAB to Resist Heme Toxicity and Uses Heme as a Signal to Induce Transcription of lmo1634, Encoding Listeria Adhesion Protein