Streptococcal peptides that signal Enterococcus faecalis cells carrying the pheromone‐responsive conjugative plasmid pAM373

Abstract

Pheromone‐mediated conjugative transfer of enterococcal plasmids can contribute to the dissemination of genes involved in antibiotic resistance, fitness, and virulence among co‐residents of mixed microbial communities. We have previously shown that intergeneric signaling by the Streptococcus gordonii strain Challis heptapeptide s.g.cAM373 (SVFILAA) induces an aggregation substance‐mediated mating response and facilitates plasmid transfer from Enterococcus faecalis cells carrying the pheromone‐responsive plasmid pAM373 to both pheromone‐producing and non‐pheromone‐producing oral streptococcal recipients. To further investigate the streptococcal pheromone‐like peptides, s.g.cAM373‐like sequences were identified in the signal sequences of streptococcal CamG lipoproteins and their abilities to induce a mating response in E. faecalis/pAM373 cells were examined. Synthetic heptamers with the consensus sequence (A/S)‐(I/V)‐F‐I‐L‐(A/V/T)‐(S/A) induced AS‐mediated clumping. The conserved pheromone ABC transporter encoded by S. gordonii genome loci SGO_RS02660 and SGO_RS02665 was identified and confirmed to be required for s.g.cAM373 activity. Functional assays of culture supernatants from representative oral and blood isolates of S. gordonii showed that in addition to strains encoding s.g.cAM373, strain SK120, encoding the newly identified pheromone s.g.cAM373‐V (SVFILVA), was able to induce enterococcal clumping, whereas strains SK6, SK8, SK9, and SK86 which encoded s.g.cAM373‐T (SVFILTA) did not elicit a detectable mating response. Absence of pheromone activity in supernatants of heterologous hosts encoding its CamG precursor suggested that s.g.cAM373‐T was not effectively processed and/or transported. Overall, these studies demonstrated the distribution of active pheromone peptides among strains of S. gordonii, and support a potential role for enterococcal–streptococcal communication in contributing to genetic plasticity in the oral metagenome.

Pheromone cCF10 inhibits the antibiotic persistence of Enterococcus faecalis by modulating energy metabolism

“…The secretion of intercellular signaling molecules among bacteria, a prevalent phenomenon, is crucially involved in bacterial behavior regulation ( Mori et al, 1984 ; Vickerman and Mansfield, 2019 ). The peptide pheromones secreted by E. faecalis can be sensed and induced by bacteria as signal molecules.…”

“…The peptide pheromones secreted by E. faecalis can be sensed and induced by bacteria as signal molecules. There are many similar pheromones such as cCF10, cAM373 and cAD 1 secreted by E. faecalis that regulate expression of conjugative plasmid transfer genes in E. faecalis ( Mori et al, 1984 ; Vickerman and Mansfield, 2019 ). Of these, pheromone cCF10 has the highest level of attention.…”

Bisphenols Promote the Pheromone-Responsive Plasmid-Mediated Conjugative Transfer of Antibiotic Resistance Genes in Enterococcus faecalis

“…At present, all the reported pheromones, including cCF10, cAM373, cPD1, and cAD1, expressed by Enterococcus, contain a benzene ring structure, which may be critical to pheromone receptor binding. Interestingly, all the bisphenols also contain the benzene ring structure.…”