S-Nitrosated Alpha-1-acid Glycoprotein Kills Drug-resistant Bacteria and Aids Survival in Sepsis

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Treating infections with exogenous NO, with broad-spectrum antimicrobial activity, seems to be effective. Similar to NO biosynthesis, biosynthesis of alpha-1-acid glycoprotein variant A (AGPa), with a reduced cysteine, increases markedly during inflammation and infection. The purpose of this study was to determine whether S-nitrosated AGPa (SNO-AGPa) may be the first compound of this novel antibacterial class against multidrug-resistant bacteria. AGPa was incubated with activated RAW264.7 cells. Results indicated that endogenous NO generated by activated RAW264.7 cells caused S-nitrosation of AGPa at Cys149. SNO-AGPa strongly inhibited growth of Gram-positive, Gram-negative, and multidrug-resistant bacteria and was an extremely potent bacteriostatic compound. Treatment with SNO-AGPa markedly reduced bacterial counts in blood and liver in a mouse sepsis model. The sialyl residues of AGPa seem to suppress the antibacterial activity, since SNO-asialo AGPa was more potent than SNO-AGPa.