Rifampin resistance mutations in the rpoB gene of Enterococcus faecalis impact host macrophage cytokine production

Antibiotic-resistant bacteria in the genus Enterococcus are a major cause of nosocomial infections and are an emergent public health concern. Similar to a number of bacterial species, resistance to the antibiotic rifampicin (Rif(R)) in enterococci is associated with mutations in the gene encoding the beta subunit of RNA polymerase (rpoB). In Mycobacterium tuberculosis, Rif(R) rpoB mutations alter mycobacterial surface lipid expression and are associated with an altered IL-1 cytokine response in macrophages upon infection. However, it is not clear if Rif(R) mutations modulate host cytokine responses by other bacteria. To address this question, we utilized Enterococcus faecalis (E. faecalis). Here, we treated human monocyte-derived macrophages with heat-inactivated wild type or Rif(R) rpoB mutants of E. faecalis and found that Rif(R) mutations reduced IL-1 beta cytokine production. However, Rif(R) mutations elicited other potent pro- and anti-inflammatory responses, indicating that they can impact other immune pathways beyond IL-1R1 signaling. Our findings suggest that immunomodulation by mutations in rpoB may be conserved across diverse bacterial species and that subversion of IL-1R1 pathway is shared by Rif(R) bacteria.

Automated summary

Mutations in the rpoB gene can modulate host cytokine responses and interfere with multiple immune pathways in antibiotic-resistant bacteria.