Antibiotics and expression of microbial virulence factors: implications for host defense.
The discovery that antibiotics are capable of modifying both the structural appearance and physiology of pathogenic bacteria when they are incorporated in the culture medium at sub-growth inhibitory concentrations, has led to numerous examples in which the expression of one or more virulence factors (both structural and soluble) is inhibited or potentiated--some of these bacterial products are recognized in their own right as substances which can interfere with one or more stages of the normal process of phagocytosis viz, chemotaxis and Staphylococcus aureus alpha-toxin; opsonization and M protein of Streptococcus pyogenes; phagocytic ingestion and capsule of Bacteroides fragilis; phagocytic killing and streptolysin O of Streptococcus pyogenes. Exposure to these bacteria to low concentrations of various chemotherapeutic drugs can alter the efficacy of the phagocytic process. However, many examples exist in which no specific biochemical lesion induced by exposure to the antibiotic has been recognized. By way of contrast some recent experimental studies using genetically defined variants of S. aureus expressing protein A, alpha-toxin, beta-toxin or coagulase have allowed some discrimination as to the specifity of the drug action and the relative role of each virulence factor in bacterial pathogenicity. In particular it can be recognized that the presence or absence of protein A either through drug treatment (clindamycin or fusidic acid) or through gene delation is critical in determining bacterial susceptibility to opson-ophagocytosis. Extension of these studies to in vivo models will shed light on possible antibiotic-host defence interaction during chemotherapy.
Gemmell
C G
CG
Department of Bacteriology, University of Glasgow Medical School, Royal Infirmary, Scotland.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D010587:Phagocytosis; D013205:Staphylococcal Protein A / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D014774:Virulence
D000900:Anti-Bacterial Agents; D013205:Staphylococcal Protein A