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 antibi otic cefpodoxime on the gram negative periodontopathic microorganism A ctinobacillus actinomycefemcomifans and its interaction with elements of the host immune system, Growth of A. actinomycetemcomitans in subin hibitory concentrations of cefpodoxime induced morphological changes i n the bacteria, causing the organisms to grow as filaments rather than coccobacilli. Growth in cefpodoxime did not render these bacteria sus ceptible to killing by serum, nor did it abrogate the requirement for serum opsonins to support the bactericidal activity of neutrophils. Ce fpodoxime enhanced the susceptibility of A. actinomycefemcomifans to t he bactericidal activity of neutrophils. In the presence of suitable o psonins, neutrophils were able to kill four times as many cefpodoxime- induced A. actinomycetemcomitans filaments as untreated A. actinomycet emcomitans CFU. This effect was due to antibiotic actions on the bacte rium and not on the neutrophil. At inhibitory concentrations, the bact ericidal activities of cefpodoxime and neutrophils were additive, and cefpodoxime did not interfere with the normal functioning of the neutr ophils. Concomitant with these morphological and functional changes, t he expression of two outer membrane proteins (86 and 29 kDa) and one i nner membrane protein (57 kDa) was decreased in A. actinomycetemcomita ns grown in cefpodoxime. The concentration range over which cefpodoxim e is effective against A. actinomycetemcomitans in vivo may be extende d by the ability of subinhibitory concentrations to enhance the suscep tibility of this organism to host immune defenses.