The incongruent gelatinase genotype and phenotype in Enterococcus faecalis are due to shutting off the ability to respond to the gelatinase biosynthesis-activating pheromone (GBAP) quorum-sensing signal

Abstract

The concomitant presence of a complete fsr quorum-sensing system and gelE-sprE operons in Enterococcus faecalis is known to be essential for the detection of gelatinase activity. However, there are reports of the absence of gelatinase activity despite the presence of complete fsr and gelE loci. In order to understand this incongruence between genotype and phenotype we sequenced fsr and gelE loci of the E. faecalis LN68 strain, which was previously found to carry both operons but to lack gelatinase activity. Of the 59 nucleotide differences detected compared with the gelatinase-positive V583 strain, we found a nonsense mutation (a premature STOP codon) predicted to truncate the ATPase sensor domain of the FsrC protein, responsible for sensing and transducing the signal from the quorum-sensing molecule. Strain LN68 was highly affected in the expression of the gelE and sprE genes, further supporting the lack of Fsrdependent gelE induction. When we constructed a V583 mutant with the same premature stop mutation in the fsrC gene the resulting strain was no longer able to degrade gelatin. We conclude that the reduced ability to transduce the quorum-sensing signal of the prematurely truncated FsrC protein is sufficient to explain the negative gelatinase phenotype. As the incongruent genotype and phenotype is detected in natural isolates, we believe that the silencing of the quorum-sensing system Fsr may be beneficial for some E. faecalis strains.

Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection

“…After internalization, AS promotes resistance to superoxide killing, leading to increased survival in macrophages (19). In addition, gelatinase is a secreted, quorum-responsive gene product that facilitates innate immune evasion by cleaving complement components C3, C3a, and C5a to reduce opsonization and decrease neutrophil recruitment (17,18,24,25).…”

Drosophila Host Model Reveals New Enterococcus faecalis Quorum-Sensing Associated Virulence Factors

“…In order to precisely identify genes for which expression is altered when GBAP reaches effective quorum sensing concentration, we used a fsrB mutant, which is unable to produce GBAP, but is able to sense it [30]. We also used single and double protease mutants in the fsrB mutant background in order to identify any genes for which expression is indirectly controlled by Fsr through its regulation of protease levels.…”

“…2009 [21]. These strains are still responsive to external GBAP, but are not able to produce the QS molecule, as is the case of VI13[V583 ΔfsrB ] [30]. Construction of KS17[V583 ΔlytSR ] and KS18[V583 ΔlrgAB ] mutants was done similarly to the method described by Thurlow et al .…”

IS256 abolishes gelatinase activity and biofilm formation in a mutant of the nosocomial pathogen Enterococcus faecalis V583

“…The gelatinase-negative phenotype has been reported for both natural and laboratory E. faecalis strains (Teixeira et al 2012). It has a number of genetic causes, mostly involving the fsr locus (Shankar et al 2012).…”