Scientific Publications by FDA Staff

Infect Immun 2016 Mar 24;84(4):1016-31

The fruRBA operon is necessary for Group A Streptococcal growth in fructose and for resistance to neutrophil killing during growth in whole human blood.

Valdes KM, Sundar GS, Vega LA, Belew AT, Islam E, Binet R, El-Sayed NM, Le Breton Y, McIver KS

Bacterial pathogens rely on the availability of nutrients for survival in the host environment. The phosphoenolpyruvate-phosphotransferase system (PTS) is a global regulatory network connecting sugar uptake with signal transduction. Since the fructose PTS has been shown to impact virulence in several Streptococci, including the human pathogen S. pyogenes (the group A Streptococcus, GAS), we characterized its role in carbon metabolism and pathogenesis in the M1T1 strain 5448. Growth in fructose as a sole carbon source resulted in 103 genes affected transcriptionally, where the fru locus (fruRBA) was the most induced. RT-PCR showed that fruRBA formed an operon, which was repressed by FruR in the absence of fructose, in addition to being under carbon catabolic repression. Growth assays and carbon utilization profiles revealed that although the entire fru operon was required for growth in fructose, FruA was the main transporter for fructose and was also involved in the utilization of three additional PTS sugars: cellobiose, mannitol, and N-acetyl-D-galactosamine. Inactivation of sloR, a fruA homolog that was also up regulated in presence of fructose, failed to reveal a role as a secondary fructose transporter. Whereas the ability of both DeltafruR and DeltafruB mutants to survive in the presence of whole human blood or neutrophils was impaired, the phenotype was not reproduced in murine whole blood, nor were those mutants attenuated in a mouse intraperitoneal infection. Since the DeltafruA mutant exhibited no phenotype in the human or mouse assays, we propose that FruR and FruB are important for GAS survival in a human-specific environment.