Neisseria meningitidis (meningococcus) is a gram negative diplococcus, which colonizes the nasopharyngeal mucosa in about 10% of healthy subjects. However, in some circumstances, the bacterium acquires invasive capacity, causing meningitis and sepsis. Although rifampicin has been used as agent for prophylaxis of meningococcal disease for more than 30 years, several cases of rifampicin-resistant meningococcal isolates have been reported. The mechanism of rifampicin resistance is associated with single point mutations of the rpoB gene, encoding the b-subunit of the RNA polymerase (RNApol), causing aminoacid substitutions that alter the binding between the polymerase and rifampicin. The spread of meningococcal RifR clinical isolates led us to analyze the phenotype of 93/4286 serogroup C strain spontaneously rifampicin-resistant. By using sequence and in silico analysis three characteristic point mutations in RpoB protein have been identified: H555Y, S551F, H555R. The selected RifR strains were tested for their ability to grow and survive in different media. Moreover, to analyze the behavior of RifR strains in stress conditions during the infectious cycle, the mutants were exposed to hydrogen peroxide (H2O2) and sodium nitroprusside (SNP) sources.

Our results suggest that the aminoacid substitutions in RpoB protein confer not only resistance to rifampicin but also to natural defenses of the human host.