Regulation of protein A biosynthesis in Staphylococcus aureus by certain antibiotics: its effect on phagocytosis by leukocytes

Abstract

Protein A, a component of the outer layer of the cell wall of Staphylococcus aureus impairs opsonization by serum complement and thereby delays phagocytosis by polymorphonuclear leukocytes. Two antibiotics with modes of action on bacterial protein biosynthesis, have been used at sub-growth inhibitory concentrations to regulate the production of protein A. Both clindamycin and fusidic acid (either at 1/2 or 1/4 MIC) reduced the amount of protein A on the cell surface. Such drug-grown cells became more susceptible to phagocytic uptake and killing. Chemiluminescence (CL) of PMN when presented with preopsonized drug-grown staphylococci was potentiated and correlated with the enhanced phagocytosis seen earlier. The level of CL appeared to depend upon the amount of human serum used to opsonize the bacteria. Reduced protein A content on the cell surface probably resulted in the exposure of a greater number of receptor sites for C3b, rendering the bacterium more susceptible to attachment and ingestion by the polymorphonuclear leukocyte.

Effect of sub‐inhibitory concentrations of antibiotics on the virulence of Staphylococcus aureus

“…It has been shown previously that the production of the toxins/enzymes of Staph. aureus can be affected by growth of the strains in certain antibiotics (Hinton and Orr 1960;Gemmell and Shibl 1976;Nordstrom and Lindberg 1978;Gemmell and O'Dowd 1983). The production of coagulase can be reduced when the producer organism is grown in the presence of sub-MIC levels of chloramphenicol, clindamycin and lincomycin (Gemmell and Shibl 1976).…”

“…Protein A production, both cell bound and extracellular, was reduced when the strains were grown in the presence of sub-MIC levels of chloramphenicol, gentamicin and tetracycline. Other protein synthesis inhibitors, clindamycin and fusidic acid, also reduce protein A production (Gemmell and O'Dowd 1983). Extracellular protein A production was reduced more significantly than cell bound protein A. I t may be that the lower amounts of extracellular protein A produced in the absence of antibiotics are reduced to undetectable levels in their presence.…”

Subinhibitory Clindamycin Differentially Inhibits Transcription of Exoprotein Genes in Staphylococcus aureus

“…For example, the decrease of protein A on the cell surface of S. aureus resulted in a greater number of free receptor sites for complement C3b and an increase in phagocytosis (7,8,22). Reduction of adherence to bone surfaces has also been observed (21), and pretreatment with subinhibitory clindamycin (SBCL) or lincomycin caused a significant reduction in the severity of skin lesions in a murine subcutaneous abscess model (5,35).…”

Phagocyte uptake and transport of azithromycin

“…The best explanation is that the two basic amine groups in azithromycin's structure may allow for greater ionisation and trapping within lysosomes than would occur with those agents containing a single basic amine group. (14). Azithromycin and macrolides may change the phenotypic expression of bacterial surface proteins and modify interactions with serum opsonins, thereby altering the interaction between bacteria and neutrophils.…”