TABLE 2 .

Regulation of virulence by CodY in Gram-positive pathogens

Organism	Phenotype of codY mutant in vivo	Notable virulence gene regulation	Reference(s)
Staphylococcus aureus	Hypervirulent in murine skin abscess and pneumonia; no effect on systemic infection	Indirect 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 pneumoniae	Reduced colonization; no effect on systemic infection	Direct activation of adhesion protein choline-binding protein (pcpA)	32
Bacillus anthracis	Attenuated virulence in murine toxinogenic model	Indirect activation of anthrax toxin components (cya, lef, pagA) and direct repression of S layer proteins (sap, eag) via AtxA; activation of iron scavenging systems	46–48
Clostridium perfringens
Type D	NTa	Direct and indirect activation of epsilon toxin (ETX); repression of sporulation	41, 54
Type A		Activation of sporulation and enterotoxin (CPE)	55
Bacillus cereus (F4810/72)	Attenuated virulence in Galleria mellonella infection model	Indirect 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 difficile	NT	Indirect repression of toxin A (tcdA) and B (tcdB) via direct repression of tcdR	53
Listeria monocytogenes	Attenuated virulence in murine systemic infection model	Indirect activation of listeriolysin O (hyl) via direct activation of regulator prfA; direct activation of flagellar biosynthesis and ActA	35, 39, 56, 57
Streptococcus pyogenes	NT	Indirect activation of surface proteins via activation of regulator mga; activation of regulators fasX and pel/sagA	61, 62

^aNT, not tested.