A newly discovered Aerococcus urinae mediates transfer of the pCF10 plasmid via SPI-WT regulation

Pheromone-regulated horizontal transfer serves as the core mechanism for horizontal gene transfer of antibiotic resistance genes, playing a pivotal role in driving the spread of resistance. Given the strict species-specific constraints of this regulatory system, it is imperative to determine whether novel regulatory signal peptides and cross-genus receptors responsive to these signals exist, thereby elucidating its potential for disseminating resistance across broader microbial communities.

This study isolated and screened a Gram-positive coccus, Aerococcus urinae Ae1, from the gut microbiota, and confirmed that Ae1 can undergo intergeneric plasmid transfer with Enterococcus faecalis (E. faecalis), challenging the conventional understanding that the pCF10 plasmid spreads only within the same species.

Results showed an intergeneric plasmid transfer frequency of (3.41 ± 0.26) × 10^-3 in Ae1, which increased to (7.97 ± 1.77) × 10^-3 upon exogenous addition of the cCF10 signal peptide, indicating cCF10's regulatory role in this process. Furthermore, the Ae1 signal peptide SPI-WT appeared to functionally resemble the cCF10 mechanism, possibly by acting on the prgZ/prgX pathway to promote pCF10 intergeneric transfer. This study suggests that Aerococcus urinae can acquire the pCF10 plasmid via intergeneric transfer and provides preliminary evidence that its endogenous signal peptide SPI-WT may play a regulatory role via the prgZ/prgX pathway. However, direct proof of natural secretion, physical binding, intracellular uptake, and relief of transcriptional repression is lacking; these remain important questions for future investigation. Nonetheless, our findings provide new insights into the dissemination pathways of intestinal antibiotic resistance genes.