TY - JOUR
T1 - The response regulator Rrp2 is essential for the expression of major membrane lipoproteins in Borrelia burgdorferi
AU - Yang, Xiaofeng F.
AU - Alani, Sophie M.
AU - Norgard, Michael V.
PY - 2003/9/16
Y1 - 2003/9/16
N2 - Borrelia burgdorferi (Bb), the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. As Bb transitions between its two diverse niches, profound adaptive changes occur that are reflected in differential patterns of gene expression, particularly involving lipoprotein genes. Using a mutagenesis approach, we show that Rrp2 (gene BB0763), one of the proteins predicted by the Bb genome (www.tigr.org) to be a response regulator of a two-component sensory transduction system, is a pivotal regulator governing the expression of major membrane lipoproteins such as OspC, DbpA, and MIp8, as well as many other mammalian infection-associated immunogens of Bb. Sequence analysis additionally suggested that Rrp2 is a bacterial enhancer-binding protein, essential for σ 54-dependent gene activation. Mutagenesis of a key amino acid residue within a putative activation domain revealed that Rrp2 controlled lipoprotein expression by governing the expression of the alternative σ-factor σs in a σ54-dependent manner. We therefore propose a signal transduction pathway involving Rrp2, σ 54, and σs, which in concert control the expression of key lipoproteins and other infection-associated immunogens in Bb.
AB - Borrelia burgdorferi (Bb), the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. As Bb transitions between its two diverse niches, profound adaptive changes occur that are reflected in differential patterns of gene expression, particularly involving lipoprotein genes. Using a mutagenesis approach, we show that Rrp2 (gene BB0763), one of the proteins predicted by the Bb genome (www.tigr.org) to be a response regulator of a two-component sensory transduction system, is a pivotal regulator governing the expression of major membrane lipoproteins such as OspC, DbpA, and MIp8, as well as many other mammalian infection-associated immunogens of Bb. Sequence analysis additionally suggested that Rrp2 is a bacterial enhancer-binding protein, essential for σ 54-dependent gene activation. Mutagenesis of a key amino acid residue within a putative activation domain revealed that Rrp2 controlled lipoprotein expression by governing the expression of the alternative σ-factor σs in a σ54-dependent manner. We therefore propose a signal transduction pathway involving Rrp2, σ 54, and σs, which in concert control the expression of key lipoproteins and other infection-associated immunogens in Bb.
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U2 - 10.1073/pnas.1834315100
DO - 10.1073/pnas.1834315100
M3 - Article
C2 - 12949258
AN - SCOPUS:0141814623
SN - 0027-8424
VL - 100
SP - 11001
EP - 11006
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -