Encapsulation in Bacteroides species has been thoroughly studied in vivo as a virulence factor in abscess formation. Its pathogenic role in lethal infections caused by a mixture of pathogens has been less well investigated. Our previous studies using the rat fibrin clot peritonitis model have demonstrated lethal synergy between Bacteroides fragilis and Escherichia coli. In order to determine the synergistic role of the encapsulation of the Bacteroides component in this model, inoculations of E. coli plus one of seven Bacteroides strains of differing degrees of encapsulation were assessed for their effect on mortality. Both unencapsulated Bacteroides strains tested (B. distasonis 1244, B. vulgatus 4300) produced an early lethal synergistic effect with E. coli while the heavily encapsulated strain, B. thetaiotaomicron 1603 did not do so. The four other Bacteroides strains tested were encapsulated and their synergy with E. coli was demonstrated. Control Gram-positive strains, Streptococcus faecalis and Staphylococcus aureus, did not alter mortality when mixed with E. coli in this model. These studies support the concept that virulence factors other than encapsulation are important in the outcome of polymicrobial infections in which Bacteroides species play a part.
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While demonstrating that encapsulation is not the critical factor for lethal synergy, none of our results help to determine the true mechanism for synergy in this model. Several mechanisms are possible z6 including bacteria providing nutrients and improving the local milieu for each other. The mechanism that has received recent attention, however, has been the ability of one bacterial species to inhibit the phagocytic response directed against other bacterial species in a mixture. Several in vitro studies have shown that anaerobes can inhibit phagocytic killing of selected facultative bacteria by neutrophils.21, 26-31 Whether this effect is due to a bacterial cell-associated factor or a substance in solution is unclear. Namavar and colleagues 21 linked the inhibitory effect to the liquid phase and demonstrated that a heat-stable low molecular weight substance ( < 35oo MW) was responsible. We have shown that a substance present in the culture filtrate of both encapsulated and unencapsulated Bacteroides species can impair neutrophil chemotactic and random migration. 37 Short chain fatty acids, which are major metabolic products of Bacteroides species, 3s are good but unproven candidates for producing this phenomenon, zg' 40 (This work was supported by the Medical Research Council of Canada and Public Health Service grants nos. AI 14302 and AI 21475 from the National Institute of Health. The authors wish to thank Miss Christina Wareham for helping in the preparation of the manuscript.)