Subinhibitory concentrations of cefpodoxime alter membrane protein expression of Actinobacillus actinomycetemcomitans and enhance its susceptibility to killing by neutrophils.

The aim of the present study was to determine the effect of the antibiotic cefpodoxime on the gram-negative periodontopathic microorganism Actinobacillus actinomycetemcomitans and its interaction with elements of the host immune system. Growth of A. actinomycetemcomitans in subinhibitory concentrations of cefpodoxime induced morphological changes in the bacteria, causing the organisms to grow as filaments rather than coccobacilli. Growth in cefpodoxime did not render these bacteria susceptible to killing by serum, nor did it abrogate the requirement for serum opsonins to support the bactericidal activity of neutrophils. Cefpodoxime enhanced the susceptibility of A. actinomycetemcomitans to the bactericidal activity of neutrophils. In the presence of suitable opsonins, neutrophils were able to kill four times as many cefpodoxime-induced A. actinomycetemcomitans filaments as untreated A. actinomycetemcomitans CFU. This effect was due to antibiotic actions on the bacterium and not on the neutrophil. At inhibitory concentrations, the bactericidal activities of cefpodoxime and neutrophils were additive, and cefpodoxime did not interfere with the normal functioning of the neutrophils. Concomitant with these morphological and functional changes, the expression of two outer membrane proteins (66 and 29 kDa) and one inner membrane protein (57 kDa) was decreased in A. actinomycetemcomitans grown in cefpodoxime. The concentration range over which cefpodoxime is effective against A. actinomycetemcomitans in vivo may be extended by the ability of subinhibitory concentrations to enhance the susceptibility of this organism to host immune defenses.