Mac-2, but not enzymatically inactive Mac-2M28, confers resistance against phagocytic killing of S. pyogenes. Whole human immune blood was treated with either Mac-2M28, the enzymatically active Mac-2M28C257Y mutant protein, Mac-2M8, the enzymatically inactive Mac-2M8Y257C mutant protein, Mac-2M12, Mac-2M89, IdeSM77 (gray bar), IdeSM1 (gray bar), or a buffer control (PBS). Blood samples were inoculated with S. pyogenes and incubated at 37°C. Bacterial survival rates are shown as number of CFU at 30 min divided by the number of CFU at time zero. All values are means ± standard deviation. **, P < 0.01 compared to the buffer control; and ***, P < 0.001 between wild-type and mutant protein variants (Student's t test).