Enterococcal Rgg-Like Regulator ElrR Activates Expression of the elrA Operon

Abstract

The Enterococcus faecalis leucine-rich protein ElrA promotes virulence by stimulating bacterial persistence in macrophages and production of the interleukin-6 (IL-6) cytokine. The ElrA protein is encoded within an operon that is poorly expressed under laboratory conditions but induced in vivo. In this study, we identify ef2687 (renamed elrR), which encodes a member of the Rgg (regulator gene for glucosyltransferase) family of putative regulatory proteins. Using quantitative reverse transcription-PCR, translational lacZ fusions, and electrophoretic mobility shift assays, we demonstrate that ElrR positively regulates expression of elrA. These results correlate with the attenuated virulence of the ⌬elrR strain in a mouse peritonitis model. Virulence of simple and double elrR and elrA deletion mutants also suggests a remaining ElrR-independent expression of elrA in vivo and additional virulence-related genes controlled by ElrR.

Peptide pheromone signaling inStreptococcusandEnterococcus

“…first defined the role of Rgg in S. gordonii as a regulator gene of glucosyltransferases (Sulavik et al ., ; Sulavik & Clewell, ). Rgg‐like regulators (sometimes called MutR) have since been found in a wide range of Gram‐positive bacteria (Sanders et al ., ; Chaussee et al ., ; Qi et al ., ; Samen et al ., ; Ibrahim et al ., ; Chang et al ., ; Dumoulin et al ., ) and control a variety of bacterial processes, including production of the cysteine proteinase SpeB in S. pyogenes (Lyon et al ., ; Chaussee et al ., ), S. mutans lantibiotic bacteriocin production (Qi et al ., ), and virulence gene regulation in S. agalactiae (Samen et al ., ), among others. Only in recent years were Rgg members, once considered to be ‘stand‐alone regulators’ (Kreikmeier et al ., ), shown to respond to SHPs that serve as pheromones.…”

Overexpression of Enterococcus faecalis elr operon protects from phagocytosis

“…ElrA is encoded by the elr operon , which encodes two other WxL surface proteins, a small LPXTG-motif protein and a putative transmembrane protein proposed to form cell surface complexes [ 1 – 4 ]. Expression of the elr operon is under the control of the positive regulator elrR [ 4 , 5 ]. The elrA gene is poorly expressed in vitro , but it can be induced by complex biological milieu such as serum or urine, which suggests the tightly regulated control of elrA expression in response to in vivo signals [ 5 , 6 ].…”

“…Expression of the elr operon is under the control of the positive regulator elrR [ 4 , 5 ]. The elrA gene is poorly expressed in vitro , but it can be induced by complex biological milieu such as serum or urine, which suggests the tightly regulated control of elrA expression in response to in vivo signals [ 5 , 6 ]. Previously, we showed that inactivation of the elrA gene resulted in significantly reduced virulence in a mouse model of peritonitis [ 4 ].…”

Estudos cristalográficos da proteína ElrR, regulador transcricional do fator de virulência ElrA de <i>Enterococcus faecalis</i>, e indícios de sua interação com a região de ligação ao DNA

“…Ou seja, uma proteína formada apenas por alfa-hélices, como predito para a família de RT Rgg (RRNPP). 71,98 Com essa informação, foram selecionadas estruturas de reguladores transcricionais (homólogos estruturais) com apenas alfa-hélices e que possuíam a estrutura terciária predita para a família RRNPP, para utilizar como modelo de busca no método de substituição molecular. Ao todo, três estruturas foram obtidas provenientes de três diferentes tipos de cristais de ElrR6HIS, em grupos espaciais distintos.…”

“…106 Como apenas um sítio de DNA foi determinado, para ligação deste RT, 71 sua unidade biologicamente ativa mais provável deve ser o dímero.…”