Bacterial defense mechanism could lead to new antibiotics targeting virulence
Scientists have identified how a bacterial protein called ProQ shields harmful RNA from destruction, enabling pathogens like Salmonella to cause infection. The discovery reveals a potential drug target: blocking this protection mechanism could disable bacteria's ability to form biofilms and survive inside host cells, offering a pathway for developing antibiotics that work differently than current treatments.
Originaltitel: ProQ prevents mRNA degradation through inhibition of poly(A) polymerase
<p>The RNA-binding protein ProQ interacts with many transcripts in the bacterial cell. ProQ binding is associated with increased messenger RNA (mRNA) levels, but a mechanistic explanation for this effect has been lacking. In Salmonella Typhimurium, ProQ affects key traits associated with infection, including motility and intracellular survival. However, the direct links between ProQ activity and these phenotypes are not well understood. Here, we demonstrate that ProQ promotes biofilm formation, another virulence-associated phenotype. This effect is strictly dependent on sigma factor RpoS. ProQ increases both RpoS protein and rpoS mRNA levels, but neither affects rpoS transcription nor translation. The rpoS mRNA is a ProQ target, and expression of the rpoS 3′UTR alone is strongly dependent on ProQ. RpoS expression becomes independent of ProQ in strains lacking poly(A) polymerase I (PAPI), indicating that ProQ protects against 3′ end-dependent decay. Indeed, purified ProQ inhibits PAPI-mediated polyadenylation at RNA 3′ ends. Finally, PAPI is required for ProQ’s effect on expression of genes involved in biofilm, motility, osmotic stress, and virulence, indicating that inhibition of polyadenylation is a general function of ProQ.</p>