DNA Binding by BosR Controls RpoS-Dependent and -Independent Gene Expression in Borrelia burgdorferi

Area of Science:

• Microbiology
• Molecular Biology
• Genomics

Background:

• BosR is a key regulator in Borrelia burgdorferi, essential for adaptation to the mammalian host.
• It was previously thought to primarily regulate oxidative stress genes and activate rpoS.

Purpose of the Study:

• To elucidate the global regulatory functions of BosR in Borrelia burgdorferi.
• To determine the role of BosR's DNA-binding activity in its regulatory mechanisms.
• To investigate BosR's impact on gene expression under both in vitro and host-adapted conditions.

Main Methods:

• RNA sequencing (RNA-seq) was employed to analyze gene expression changes.
• A DNA-binding-defective mutant (BosR-R39A) was used to assess the necessity of DNA binding.
• Comparative analysis was performed under in vitro and mammalian host-adapted conditions.

Main Results:

• BosR controls gene expression via both RpoS-dependent and RpoS-independent mechanisms.
• DNA binding is essential for BosR's global regulatory roles.
• BosR activates rpoS and modulates genes involved in genome maintenance, chemotaxis, and virulence, but not canonical oxidative stress genes.

Conclusions:

• BosR exhibits a bifunctional regulatory model, collaborating with RNAP-RpoS for some genes and acting independently for others.
• Its regulatory scope is broad, influencing diverse cellular functions beyond oxidative stress.
• The lack of a conserved DNA-binding motif suggests context-dependent DNA occupancy.