Differential Release of Lipoteichoic and Teichoic Acids from Streptococcus pneumoniae as a Result of Exposure to β-Lactam Antibiotics, Rifamycins, Trovafloxacin, and Quinupristin-Dalfopristin

Abstract

The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem, rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a concentration of 10 μg/ml, a rapid and intense release of LTA and TA occurred during exposure to ceftriaxone (3,248 ± 1,688 ng/ml at 3 h and 3,827 ± 2,133 ng/ml at 12 h) and meropenem (2,464 ± 1,081 ng/ml at 3 h and 2,900 ± 1,364 ng/ml at 12 h). Three hours after exposure to rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin, mean LTA and TA concentrations of less than 460 ng/ml were observed (for each group,P < 0.01 versus the concentrations after exposure to ceftriaxone). After 12 h of treatment, the LTA and TA concentrations were 463 ± 126 ng/ml after exposure to rifampin, 669 ± 303 ng/ml after exposure to rifabutin, and 1,236 ± 772 ng/ml after exposure to quinupristin-dalfopristin (for each group,P < 0.05 versus the concentrations after exposure to ceftriaxone) and 1,745 ± 1,185 ng/ml after exposure to trovafloxacin (P = 0.12 versus the concentration after exposure to ceftriaxone). At 10 μg/ml, bactericidal antibacterial agents that do not primarily affect cell wall synthesis reduced the amount of LTA and TA released during their cidal action againstS. pneumoniae in comparison with the amount released after exposure to β-lactams. Larger quantities of LTA and TA were released after treatment with low concentrations (1× the MIC and 1× the minimum bactericidal concentration) than after no treatment for all antibacterial agents except the rifamycins. This does not support the concept of using a low first antibiotic dose to prevent the release of proinflammatory cell wall components.

Effect of lipoteichoic acid on the uptake of Streptococcus pyogenes by HEp-2 cells

“…This notion is supported by the observation that LTA also inhibited the uptake but not adhesion of Salmonella, which does not produce LTA. The ¢ndings that several oral streptococci secrete high amounts of LTA during their growth [31] and that antibiotics enhance LTA secretion [16,32] suggest that local LTA concentration above CMC might also occur in vivo and has a biological relevance.…”

Effect of lipoteichoic acid on the uptake ofStreptococcus pyogenesby HEp-2 cells

“…This notion is supported by the observation that LTA also inhibited the uptake but not adhesion of Salmonella , which does not produce LTA. The findings that several oral streptococci secrete high amounts of LTA during their growth [31] and that antibiotics enhance LTA secretion [16,32] suggest that local LTA concentration above CMC might also occur in vivo and has a biological relevance.…”

Moxifloxacin in the Therapy of Experimental Pneumococcal Meningitis

“…The MICs and minimum bactericidal concentrations (MBCs) of moxifloxacin and ceftriaxone for the S. pneumoniae type 3 strain used in this and previous studies (19,21,29,33) were determined by the macrodilution method in tryptic soy broth. Furthermore, the bactericidal activity of moxifloxacin was studied at different antibacterial concentrations in tryptic soy broth (27). After overnight growth, the bacteria were suspended in fresh medium at a concentration of approximately 5 ϫ 10 8 CFU/ml prior to the initiation of treatment.…”

“…Unlike ␤-lactam antibiotics, quinolones do not kill bacteria by direct lysis of the cell wall. After the initiation of therapy they release proinflammatory cell wall products less rapidly than ␤-lactam antibiotics (21,27).…”