Alternate Sigma Factor RpoS Is Required for the In Vivo-Specific Repression ofBorrelia burgdorferiPlasmid lp54-BorneospAandlp6.6Genes

Abstract

While numerous positively regulated loci have been characterized during the enzootic cycle of Borrelia burgdorferi, very little is known about the mechanism(s) involved in the repression of borrelial loci either during tick feeding or within the mammalian host. Here, we report that the alternative sigma factor RpoS is required for the in vivo-specific repression of at least two RpoD-dependent B. burgdorferi loci, ospA and lp6.6. The downregulation of ospA and Ip6.6 appears to require either a repressor molecule whose expression is RpoS dependent or an accessory factor which enables RpoS to directly interact with the ospA and Ip6.6 promoter elements, thereby blocking transcription by RpoD. The central role for RpoS during the earliest stages of host adaptation suggests that tick feeding imparts signals to spirochetes that trigger the RpoS-dependent repression, as well as expression, of in vivo-specific virulence factors critical for the tick-to-mammalian host transition.

Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi

“…Earlier studies have shown that bba62, which encodes the Lp6.6 lipoprotein, is strongly downregulated in an RpoS-dependent manner when B. burgdorferi is cultivated in DMCs implanted into the peritoneal cavities of rats (i.e. under mammalian infection-like conditions) (Caimano et al, 2005(Caimano et al, , 2007. In agreement with these findings, bba62 was downregulated in B. burgdorferi by RpoS in our study, even under in vitro culture conditions.…”

“…Plasmid lp54 has been implicated as being important for the survival of B. burgdorferi in both tick and mammalian hosts, largely because of the presence of the ospAB and dbpBA operons (Caimano et al, 2005;Hagman et al, 1998;Neelakanta et al, 2007;Shi et al, 2008;Yang et al, 2004). Many other genes encoded on lp54 have been found to be differentially regulated in response to temperature, pH and other mammalian-derived signals, which are presumed to be mediated, at least in part, by RpoS (Caimano et al, 2005;Clifton et al, 2006;Ojaimi et al, 2003;Revel et al, 2002). Consistent with these previous findings, our data provided further evidence that 22 lp54-encoded genes are regulated by RpoS.…”

“…Along these lines, our laboratory and others have previously reported the existence in B. burgdorferi of an alternative sigma factor (RpoN/s 54 -RpoS/s S ) regulatory cascade that governs the expression of outer surface (lipo)protein C (OspC), decorin-binding protein A (DbpA), multicopy lipoprotein-8 (Mlp8), fibronectinbinding protein BBK32, and other potential virulenceassociated proteins (Caimano et al, 2004(Caimano et al, , 2005(Caimano et al, , 2007Fisher et al, 2005;He et al, 2007;Hubner et al, 2001;Smith et al, 2007;Yang et al, 2003aYang et al, , b, 2005. In this regulatory pathway, Rrp2, a putative response regulator (enhancer-binding protein) of a two-component sensory transduction system, is likely activated via phosphorylation through a histidine kinase (Hk2) (Fraser et al, 1997;Yang et al, 2003a).…”

“…Are there indirect effects; does the pathway regulate other regulators? Are there genes also downregulated by the pathway, as has been implied by the reciprocal regulation of OspC and OspA (Caimano et al, 2005;Schwan et al, 1995;Schwan & Piesman, 2000)? Does Rrp2 activation serve only to allow RpoN-dependent transcription, or does the putative DNA-binding domain of Rrp2 serve some other function(s) in B. burgdorferi?…”

Biological Aspects of Lyme Disease Spirochetes: Unique Bacteria of the Borrelia Burgdorferi Species Group

“…RpoS induces expression of temperature inducible Biological aspects of Lyme disease spirochetes: Unique bacteria of the Borrelia burgdorferi species group genes, like OspC, OspF and DbpA. In contrast, expression of OspA is dependent on housekeeping factor RpoD (σ 70 ) and is downregulated by the RpoS dependent pathway [132][133][134] .…”