Histophilus somni is capable of intracellular survival within professional 
phagocytic cells, but the mechanism of survival is not understood. The Fic motif 
within the direct repeat (DR1)/DR2 domains of the IbpA fibrillary network 
protein of H. somni is cytotoxic to epithelial and phagocytic cells, which may 
interfere with the bactericidal activity of these cells. To determine the 
contribution of IbpA and Fic to resistance to host defenses, H. somni strains 
and mutants that lacked all or a region of ibpA (including the DR1/DR2 regions) 
were tested for survival in bovine monocytic cells and for serum susceptibility. 
An H. somni mutant lacking IbpA, but not the DR1/DR2 region within ibpA, was 
more susceptible to killing by antiserum than the parent, indicating that the 
entire protein was associated with serum resistance. H. somni strains expressing 
IbpA replicated in bovine monocytes for at least 72 h and were toxic for these 
cells. Virulent strain 2336 mutants lacking the entire ibpA gene or both DR1 and 
DR2 were not toxic to the monocytes but still survived within the monocytes for 
at least 72 h. Monitoring of intracellular trafficking of H. somni with 
monoclonal antibodies to phagosomal markers indicated that the early phagosomal 
marker early endosome antigen 1 colocalized with all isolates tested, but only 
strains that could survive intracellularly did not colocalize with the late 
lysosomal marker lysosome-associated membrane protein 2 and prevented the 
acidification of phagosomes. These results indicated that virulent isolates of 
H. somni were capable of surviving within phagocytic cells through interference 
in phagosome-lysosome maturation. Therefore, H. somni may be considered a 
permissive intracellular pathogen.