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

Abstract

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 β subunit of RNA polymerase (rpoB). In Mycobacterium tuberculosis, Rif^RrpoB 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^RrpoB mutants of E. faecalis and found that Rif^R mutations reduced IL-1β 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.

Keywords: Enterococcus faecalis; IL-1β; Macrophage; Nosocomial infection; Rifampicin resistance mutation; rpoB gene.