ACTIONS OF β-LACTAM ANTIBIOTICS AGAINST PSEUDOMONAS AERUGINOSA
Their Effects on Penicillin-Binding Proteins and on Bactericidal Activity of Macrophages
1983 Volume 74 Issue 12 Pages 2031-2042
Details
1983 Volume 74 Issue 12 Pages 2031-2042
Infection of the urinary tract is one of the most important diseases in the urological field. In recent years, the frequency of clinical isolates of Pseudomonas aeruginosa from urine obtained from patients with urinary tract infection has declined considerably, most likely due to the development of antipseudomonal antibiotics. However, the treatment of the urinary tract infection with P. aeruginosa remains to be difficult.
For the purpose of clarification of the mechanism of the antibacterial activity of β-lactam antibiotics against P. aerguinosa, their morphological responses (cell growth, division and lysis) and binding affinities to penicillin-binding proteins (PBPs) were studied.
The agents CBPC, SBPC, TIPC and CTX inhibited cell growth and caused cell lysis at a low concentration, but PIPC, MZPC, APPC, CPZ and CFS arrested cell division and turned the shape of P. aeruginosa into filamentous cells. No cell lysis was caused at a high concentration. P. aeruginosa has six major PBPs, which are designated as PBP 1a, 1b, 2, 3, 4 and 5. All β-lactams exhibited high affinity to PBP 3 and CBPC, SBPC, TIPC and CTX bound to both PBP 1a, and 1b at a low concentration. In this study it was assumed that β-lactams which had high affinity to both PBP 1a and 1b caused cell lysis easily as in the cases of CBPC, SBPC, TIPC and CTX.
The effects of β-lactams on macrophage phagocytic and killing activity of P. aeruginosa are summarized as in the following. On antibioticfree control culture, the count of viable cells in macrophages increased. Cells pretreated with CBPC, CTX, CAZ or CA, however, caused a greater degree of decline of viable cells than the untreated control cells.
Morphological changes were observed with a scanning electron microscope. Elongated cells pretreated with antibiotics were subject to phagocytosis and were digested by the macrophages, but the untreated control cells showed an increase in the macrophages and caused their lysis.
