Effect of erythromycin on Shigella infection of Caco-2 cells

Abstract

Erythromycin (EM), one of the macrolides, shows a dose-dependent effect on Shigella flexneri invasion of Caco-2 cells even at concentrations less than the minimum inhibitory concentration (subMIC). LS13, a strain of S. flexneri 1b, invaded Caco-2 cells in vitro. When the strain was treated with subMIC of EM, the invasion efficiency decreased. The carrier rate of the invasion plasmid containing virulence genes was reduced by EM treatment, as determined by the colony pigmentation test on Congo red agar plates. Presence of the invasion plasmid was found to increase susceptibility of the organisms to EM. The growth of virulent organisms carrying the invasion plasmid was inhibited at 25 microg ml(-1) of EM, whereas the growth of organisms without the plasmid was inhibited at 100 microg ml(-1) of EM. This was supported by the finding that the MIC of EM for a virulent isolate of S. flexneri 2a YSH6000 (6.25 microg ml(-1)) and for the mutant strain del-17 (50 microg ml(-1)), carrying the type III apparatus, impaired plasmid. These findings suggested that EM passed through the type III apparatus and suppressed the growth of invasive organisms selectively. This mechanism may account for the clinical effect of EM on shigellosis.

Lactobacillus acidophilus (strain LB) from the resident adult human gastrointestinal microflora exerts activity against brush border damage promoted by a diarrhoeagenic Escherichia coli in human enterocyte-like cells

“…An identical mechanism of actionthat is, inhibition of the cross talk between a pathogen and target host cells-has previously been reported with antibiotics. [44][45][46][47] One of the major roles of the gut microflora is as a barrier against colonisation of the gastrointestinal tract by pathogenic bacteria. The present report provides new insight into the mechanism by which species of the human gut microflora exert a protective role against pathogens.…”

Enhanced anti-Shigellaactivity of erythromycin supplemented with sulfadiazine

“…The virulent organisms presented pigmented colonies (Pcr+), and the plasmid‐free organisms white non‐pigmented colonies (Pcr−). The presence of the invasion plasmid was confirmed in some colonies by PCR or Southern blot analysis as described [2].…”

“…The sub‐MIC culture media (2 −1 MIC, 2 −2 MIC, 2 −3 MIC) of Pcr+ or Pcr− organisms were diluted 10‐fold and inoculated onto Congo red agar plates. By enumerating the Pcr+ colonies on the agar plates inoculated with sub‐MIC culture media of Pcr+, the lowest concentration inhibiting the growth of the Pcr+ organisms, in which the number of the Pcr+ bacteria was about 7×10 5 CFU ml −1 , was finally determined as the MIC against the Pcr+ organisms [2].…”

“…Although Shigella is resistant to EM in the laboratory, the use of EM is clinically beneficial. The reasons why were partially elucidated by Honma et al [2], who showed that Shigella harboring the invasive plasmid on which the pathogenicity depends was more sensitive to EM than the plasmid‐free non‐pathogenic Shigella . EM inhibited the invasive activity of Shigella in Caco‐2 cells by penetrating the bacterial cells utilizing the type III secretion apparatus [2].…”

Enhanced anti-Shigella activity of erythromycin supplemented with sulfadiazine

“…Although Shigella is resistant to EM in the laboratory, the use of EM is clinically bene¢cial. The reasons why were partially elucidated by Honma et al [2], who showed that Shigella harboring the invasive plasmid on which the pathogenicity depends was more sensitive to EM than the plasmid-free nonpathogenic Shigella. EM inhibited the invasive activity of Shigella in Caco-2 cells by penetrating the bacterial cells utilizing the type III secretion apparatus [2].…”