TABLE 2 

Regulation of virulence by CodY in Gram-positive pathogens

OrganismPhenotype of codY mutant in vivoNotable virulence gene regulationReference(s)
Staphylococcus aureusHypervirulent in murine skin abscess and pneumonia; no effect on systemic infectionIndirect repression of delta-toxin/RNAIII via repression of agr activator; direct repression of biofilm synthesis (icaADBC), alpha-toxin (hla), hyaluronidase (hysA), Panton-Valentine leucocidin (lukSF-PV)37, 59, 167, 168
Streptococcus pneumoniaeReduced colonization; no effect on systemic infectionDirect activation of adhesion protein choline-binding protein (pcpA)32
Bacillus anthracisAttenuated virulence in murine toxinogenic modelIndirect activation of anthrax toxin components (cya, lef, pagA) and direct repression of S layer proteins (sap, eag) via AtxA; activation of iron scavenging systems46–48
Clostridium perfringens
    Type DNTaDirect and indirect activation of epsilon toxin (ETX); repression of sporulation41, 54
    Type AActivation of sporulation and enterotoxin (CPE)55
Bacillus cereus (F4810/72)Attenuated virulence in Galleria mellonella infection modelIndirect activation of cytotoxin (cytK), enterotoxin (nhe), and hemolysin (hbl) via direct activation of regulator plcR; direct repression of cereulide (cesPTABCD) and inhibitor metalloprotease 1 (inhA1)50
Clostridium difficileNTIndirect repression of toxin A (tcdA) and B (tcdB) via direct repression of tcdR53
Listeria monocytogenesAttenuated virulence in murine systemic infection modelIndirect activation of listeriolysin O (hyl) via direct activation of regulator prfA; direct activation of flagellar biosynthesis and ActA35, 39, 56, 57
Streptococcus pyogenesNTIndirect activation of surface proteins via activation of regulator mga; activation of regulators fasX and pel/sagA61, 62
  • a NT, not tested.