Bacteria of the genus Enterococcus are the main causes of highly antibiotic-resistant infections that are acquired in hospitals. Many clinical isolates of Enterococcus faecalis produce an exotoxin called cytolysin that contributes to bacterial virulence. In addition to its toxin activity, the cytolysin is bactericidal for nearly all Gram-positive organisms. An understanding of conditions that regulate cytolysin expression has advanced little since its initial description. Here we show that the products of two genes, cylR1 and cylR2, which lack homologues of known function, work together to repress transcription of cytolysin genes. Derepression occurs at a specific cell density when one of the cytolysin subunits reaches an extracellular threshold concentration. These observations form the basis of a model for the autoinduction of the cytolysin by a quorum-sensing mechanism involving a two-component regulatory system.
Many virulent strains of Enterococcus faecalis produce a two-subunit toxin, termed cytolysin. Cytolysin expression is regulated by one of the subunits (CylL(S)'') through a quorum-sensing autoinduction mechanism. We found that when target cells are absent, the other subunit (CylL(L)'') forms a complex with CylL(S)'', blocking it from autoinducing the operon. When target cells are present, however, CylL(L)'' binds preferentially to the target, allowing free CylL(S)'' to accumulate above the induction threshold. Thus, enterococci use CylL(L)'' to actively probe the environment for target cells, and when target cells are detected, allows the organism to express high levels of cytolysin in response.
The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell–cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority.
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