The elusive determinants of bacterial interference with non-specific host defences

Abstract

The identification of the determinants of bacterial interference with non-specific host defences during the early stages of infection is approached rather than attained. Recognizing a relevant biological property (e.g. resistance to phagocytosis) by an in vitro test and associating bacterial surface components with it are relatively easy. Proving causation, however, is usually not completed because the biological test is complex and the surface component(s) act only in situ . Nevertheless, evidence in addition to mere association can be sought to show that a putative determinant is strongly implicated in biological activity. Even then, proving that the biological activity concerned is relevant to infection in vivo , and that the putative determinant is produced there, is often not accomplished. Again, however, distinction can be made between those cases probably relevant in vivo and those only possibly so. Finally, bacteria grown in vitro can be deficient in some of the determinants of pathogenicity expressed during infection, and this situation requires the study of organisms grown in vivo . These points are discussed and then illustrated in a brief survey of the activities of many pathogenic bacteria and a description of recent work on the resistance of gonococci to killing by human serum and phagocytes.

Topological and mutational analysis of KpsM, the hydrophobic component of the ABC‐transporter involved in the export of polysialic acid in Escherichia coli K1

“…As the outermost structures on the bacteriai celi, capsular poiysaccharides play a critical role in the interaction Received 13 June, 1994;revised 9 August, 1994;accepled 15 August, 1994, *For correspondence. E-mail Ripsi ©bphvax, biophysics.rochester.edu; Tel, (716) 275 0680: Fax (716) -173 9573. between a microorganism and its environment (Peterson and Quie, 1981;Smith, 1983). Capsules have long been recognized as important virulence determinants of bacteria able to invade the human host and survive in the bloodstream (Cross, 1990;Moxon and Kroll, 1990).…”

The Revival of Interest in Mechanisms of Bacterial Pathogenicity

“…Similar tests should be done on virulent strains grown in vivo and in oitro (see above). Although inhibition of serum killing and prevention of ingestion by phagocytes still receive most attention, tests for interference with host defences now include prevention of complement activation or action, inhibition of chemotaxis and intracellular killing by phagocytes and interference with or suppression of the immune response (O'Grady & Smith, 1981;Smith, 1983;Schwabe, 1983;Falcone et al, 1984;Roth, 1988;Kaufmann & Flesch, 1992;Penn, 1992). Now many biological tests span all facets of pathogenicity.…”

“…Over the years, hundreds of papers have been written on the subject: references to some of the more pertinent original papers are given in the following books and reviews that span 50 years (Wilson & Miles, 1947;Howie & O'Hea, 1955;Dubos & Hirsch, 1965;Smith, 1968; O'Grady & Smith, 1 9 8 1 ; Smith, 1983;Falcone et al, 1984;Roth, 1988;Kaufmann & Flesch, 1992; monocytogenes are examples. Over the years, hundreds of papers have been written on the subject: references to some of the more pertinent original papers are given in the following books and reviews that span 50 years (Wilson & Miles, 1947;Howie & O'Hea, 1955;Dubos & Hirsch, 1965;Smith, 1968; O'Grady & Smith, 1 9 8 1 ; Smith, 1983;Falcone et al, 1984;Roth, 1988;Kaufmann & Flesch, 1992; monocytogenes are examples.…”

“…Factors affecting multiplication in vivo have been revealed by bacterial growth in body fluids with and without appropriate nutrients (Griffiths,I 983). Although inhibition of serum killing and prevention of ingestion by phagocytes still receive most attention, tests for interference with host defences now include prevention of complement activation or action, inhibition of chemotaxis and intracellular killing by phagocytes and interference with or suppression of the immune response (O'Grady & Smith, 1981;Smith, 1983;Schwabe, 1983;Falcone et al, 1984;Roth, 1988;Kaufmann & Flesch, 1992;Penn, 1992). Turning to host damage, toxins are still detected by animal experiments, but increasingly by cytotoxicity to tissue culture cells (Roth, 1988;Alouf & Freer, 1991).…”

“…Since the term 'aggressin' was coined by Bail at the turn of the century, the determinants of interference with non-specific defence mechanisms have received much attention. Over the years, hundreds of papers have been written on the subject: references to some of the more pertinent original papers are given in the following books and reviews that span 50 years (Wilson & Miles, 1947;Howie & O'Hea, 1955;Dubos & Hirsch, 1965;Smith, 1968; O'Grady & Smith, 1 9 8 1 ; Smith, 1983;Falcone et al, 1984;Roth, 1988;Kaufmann & Flesch, 1992;Jann & Jann, 1992). Numerous determinants have been identified and proved relevant in vivo (steps 4 and 5).…”