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. 2005 May 14;11(18):2720-5.
doi: 10.3748/wjg.v11.i18.2720.

Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection

Zarko Babic  1 , Ivna Svoboda-Beusan, Nastja Kucisec-Tepes, Dragan Dekaris, Rosana Troskot
Affiliations

Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection

Zarko Babic et al. World J Gastroenterol. .

Abstract

Aim: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping during Helicobacter pylori (H pylori) infection treatment with classic antibiotic therapy.

Methods: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. The H pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF).

Results: Upon the first cycle, H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P<0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P<0.0001) in patients with multiple therapeutic failure than in those with successful H pylori eradication and control subjects.

Conclusion: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.

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Figures

Figure 1
Figure 1
FACS analysis of Rh123 accumulation as a function of Pgp activity (A-C): (A) GBS were stained with a fluorescent substrate Rh123 in the presence (overlaid histogram) or absence (filled histogram) of the MDR reversing agent CyA. Pgp activity is expressed as RMF, a ratio of mean fluorescences obtained from the gated viable cell population. RMF ≥1 considered positive; (B) resistant (Pgp-positive/active) and (C) sensitive (Pgp-negative/inactive) control cell lines.
Figure 2
Figure 2
Enhanced Pgp activity in patients with H pylori infection. RMF values of 53 H pylori positive patients and 12 H pylori negative (control) patients are presented (x = mean; SD = standard deviation; SE = standard error).
Figure 3
Figure 3
Therapeutic effect on Pgp activity in 10 randomly selected H pylori positive patients: significantly increased post-therapeutic RMF values.
Figure 4
Figure 4
RMF values with five therapeutic protocols: combined therapy had no effect with enhanced Pgp activity. First course: PAM (pantoprazole +amoxicillin+metronidazole), PAC (pantoprazole+amoxicillin+clarithromycin); second course: PAM+PAC, PAM+PAAZ (pantoprazole+amoxicillin+azithromycin), PAC+PAAZ.
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