Fibrinogen^AEK does not support rapid clearance of S aureus bacteria following acute peritoneal infection but retains some capacity to limit host lethality. The number of S aureus CFUs present in peritoneal lavage fluid collected 1 hour after intraperitoneal infection with (A) 0.8 × 10⁹ CFUs strain USA300 S aureus and (B) 1 × 10⁹ CFUs strain Newman S aureus from WT, Fib^AEK, Fib^+/−, and Fib^−/− mice (n = 6 per genotype). Data are presented as mean ± standard error of the mean with statistical comparisons made by Student t test. (C) Flow cytometric analysis of myeloid cell populations harvested from the peritoneal cavity of WT and Fib^AEK mice (n = 6 mice per genotype). Analyses are presented as the mean ± standard error of the mean. (D) Representative photomicrographs of cytospin preparations of peritoneal lavage fluid taken 1 hour after intraperitoneal infection with 1 × 10⁹ CFUs S aureus. Note the cell-associated and free bacteria in samples from Fib^AEK and Fib^−/− mice that are largely absent in samples from WT and Fib^+/− mice. Scale bar, 20 μm. (E) Analysis of fibrinogen-dependent bacterial clumping with suspensions of strain Newman S aureus with and without expression of clumping factor A (ClfA). Notably, both WT and fibrinogen^AEK support bacterial clumping at a concentration of 2 μg/mL and above. (F) Analyses of coagulase (Coa)-induced plasma clotting with citrate-plasma preparations from WT, homozygous Fib^AEK, and Fib^−/− mice using supernatants prepared from stationary phase cultures of both strain Newman WT (Coa⁺) S aureus and Coa-negative (Coa⁻) strain Newman S aureus. Survival analyses of WT, Fib^AEK, and Fib^−/− mice (n = 12 per genotype) following intraperitoneal infection with (G) 0.4 × 10⁹ CFUs or (H) 1 × 10⁹ CFUs strain Newman S aureus. *P < .01 for WT compared with Fib^−/− or Fib^AEK; **P < .01 for Fib^AEK compared with Fib^−/− using Kaplan-Meier log-rank analysis.