Fig. 4. Mechanism of RNA polymerase II inhibition by asymptomatic bacteriuria strains.

Asymptomatic bacteriuria (ABU) strains establish a symbiotic relationship with their host, in part by inhibiting RNA polymerase II (Pol II)-dependent gene expression. The NlpD protein, released by the bacteria, is internalized by host cells, where it targets DNA-directed RNA polymerase II subunit RPB1/POLR2A (RPB1) and the phosphorylation complex constituent polymerase-associated factor 1 complex (PAF1C), which recruits the cyclin-dependent kinase 12 (CDK12) to the complex. As a result, Pol II phosphorylation by CDK12 is inhibited and host gene expression is suppressed. Protective effects of NlpD in mice infected with the uropathogenic Escherichia coli (UPEC) strains CFT073 or CY17 have also been associated with reduced Pol II phosphorylation. P, phosphate group.