The Cellobiose Sensor CebR Is the Gatekeeper of Streptomyces scabies Pathogenicity

Abstract

A relatively small number of species in the large genus Streptomyces are pathogenic; the best characterized of these is Streptomyces scabies. The pathogenicity of S. scabies strains is dependent on the production of the nitrated diketopiperazine thaxtomin A, which is a potent plant cellulose synthesis inhibitor. Much is known about the genetic loci associated with plant virulence; however, the molecular mechanisms by which S. scabies triggers expression of thaxtomin biosynthetic genes, beyond the pathway-specific activator TxtR, are not well understood. In this study, we demonstrate that binding sites for the cellulose utilization repressor CebR occur and function within the thaxtomin biosynthetic cluster. This was an unexpected result, as CebR is devoted to primary metabolism and nutritive functions in nonpathogenic streptomycetes. In S. scabies, cellobiose and cellotriose inhibit the DNA-binding ability of CebR, leading to an increased expression of the thaxtomin biosynthetic and regulatory genes txtA, txtB, and txtR. Deletion of cebR results in constitutive thaxtomin A production and hypervirulence of S. scabies. The pathogenicity of S. scabies is thus under dual direct positive and negative transcriptional control where CebR is the cellobiose-sensing key that locks the expression of txtR, the key necessary to unlock the production of the phytotoxin. Interestingly, CebR-binding sites also lie upstream of and within the thaxtomin biosynthetic clusters in Streptomyces turgidiscabies and Streptomyces acidiscabies, suggesting that CebR is most likely an important regulator of virulence in these plant-pathogenic species as well.

The Regulator Gene <b><i>rnc</i></b> Is Closely Involved in Biofilm Formation in <b><i>Streptococcus mutans</i></b>

“…The data represent the average molecular weight for the entire polymer distribution. environment [Francis et al, 2015]. Actually, the environment in the human oral cavity is highly variable, especially with respect to pH, osmolarity, and oxygen content, which fluctuate throughout the dental plaque biofilm [Crepps et al, 2015].…”

Contribution of the β‐glucosidase BglC to the onset of the pathogenic lifestyle of Streptomyces scabies

“…This delay in the response of BG might be a consequence of the delay in (Glc) 3 consumption observed for the ΔbglC strain (Fig. A), but also because (Glc) 3 is a much weaker allosteric effector of CebR relative to (Glc) 2 (Francis et al ., ). These observations demonstrate that BglC is not the only functional BG in S. scabies to catabolize cello‐oligosaccharides.…”

“…scabies . We generated a bglC null mutant (Δ bglC ) by replacing orf scab57721 with the apramycin resistance cassette, as performed previously for cebR , cebE and msiK (Francis et al ., ; Jourdan et al ., ). Semi‐quantitative analysis by high‐performance liquid chromatography (HPLC) revealed that the Δ bglC /Δ 57721 mutant produced only 37% and 9% of the thaxtomin levels produced by the wild‐type strain when cultivated in liquid minimal medium (MM) with (Glc) 2 or (Glc) 3 as sole carbon source, respectively (Fig.…”

“… Position of β‐glucosidase activity on the modelled metabolic pathways from cellobiose [(Glc) 2 ] and cellotriose [(Glc) 3 ] transport to glycolysis and thaxtomin A production. When (Glc) 2 and (Glc) 3 are transported into the cytoplasm through the CebEFG‐MsiK transporter, they both prevent the DNA‐binding ability of the repressor CebR [(Glc) 2 does this much more efficiently than (Glc) 3 ; Francis et al ., ], thus allowing the expression of CebR‐controlled genes, including the thaxtomin biosynthetic genes ( txt cluster), cebEFG and bglC . Once expressed, BglC cleaves both the imported (Glc) 2 and (Glc) 3 .…”

Recent advances in understanding Streptomyces

“…Remarkably, the expression of some of the pathogenicity genes, including those for the phytotoxin thaxtomin, is determined in part by the cellobiose sensor CebR, the universal regulator of Streptomyces cellulolytic genes, integrating pathogenicity-linked cellulolytic activity with more ancient overall responses to cellulose-related metabolites 36 . The connection of pathogenicity with cellulose is further emphasised by the fact that thaxtomin is an inhibitor of plant cellulose synthase.…”