Iron availability and oxygen tension regulate the Yersinia Ysc type III secretion system to enable disseminated...

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Yersinia species utilize the Ysc type III secretion system (T3SS) for virulence, but its expression is tightly regulated.
• T3SS expression can trigger host innate immune responses and bacterial growth arrest, necessitating precise control.

Purpose of the Study:

• To investigate the regulatory mechanisms controlling Yersinia T3SS expression in response to environmental cues.
• To identify the role of the transcription factor IscR in mediating iron and oxygen sensing for T3SS regulation.

Main Methods:

• Analysis of Yersinia pseudotuberculosis T3SS expression under varying oxygen and iron conditions.
• Investigation of IscR binding to the lcrF promoter using genetic and biochemical approaches.
• Assessment of bacterial virulence in vivo following genetic manipulation of IscR.

Main Results:

• Yersinia T3SS expression is low in iron-rich, anaerobic conditions (intestinal lumen) and high in aerobic or iron-poor conditions.
• The [2Fe-2S] containing transcription factor IscR directly binds the lcrF promoter, regulating T3SS master regulator LcrF.
• Disruption of IscR binding to lcrF decreased Y. pseudotuberculosis systemic infection but not intestinal colonization.
• IscR functions similarly to E. coli in sensing iron and oxygen via Fe-S cluster homeostasis.
• IscR binding site conservation and iscR deletion effects in Y. pestis suggest ancient regulation of T3SS.

Conclusions:

• Yersinia pseudotuberculosis coopts the IscR iron-sulfur cluster homeostasis system to sense environmental cues and induce T3SS for virulence.
• IscR-mediated regulation of the T3SS is conserved between Y. pseudotuberculosis and Y. pestis, indicating its evolutionary importance.
• Targeting IscR regulation of T3SS presents a potential strategy for combating Yersinia infections.