Abstract
Antibiotic resistance of Helicobacter pylori, a spiral bacterium associated with gastric diseases, is a topic that has been intensively discussed in last decades. Recent discoveries indicate promising antimicrobial and antibiotic-potentiating properties of sertraline (SER), an antidepressant substance. The aim of the study, therefore, was to determine the antibacterial activity of SER in relation to antibiotic-sensitive and antibiotic-resistant H. pylori strains. The antimicrobial tests were performed using a diffusion-disk method, microdilution method, and time-killing assay. The interaction between SER and antibiotics (amoxicillin, clarithromycin, tetracycline, and metronidazole) was determined by using a checkerboard method. In addition, the study was expanded to include observations by light, fluorescence, and scanning electron microscopy. The growth inhibition zones were in the range of 19–37 mm for discs impregnated with 2 mg of SER. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) counted for 2–8 µg/mL and 4–8 µg/mL, respectively. The time-killing assay showed the time-dependent and concentration-dependent bactericidal activity of SER. Bacteria exposed to MBCs (but not sub-MICs and MICs ≠ MBCs) underwent morphological transformation into coccoid forms. This mechanism, however, was not protective because these cells after a 24-h incubation had a several-fold reduced green/red fluorescence ratio compared to the control. Using the checkerboard assay, a synergistic/additive interaction of SER with all four antibiotics tested was demonstrated. These results indicate that SER may be a promising anti-H. pylori compound.
Highlights
The presence of spiral microorganisms inhabiting the gastric mucosa was noticed more than 100 years ago, but the lack of a way to isolate these microorganisms using standard culture methods probably reduced interest in this topic [1]
Antibiotic resistance of H. pylori strains did not determine the size of the growth inhibition zones produced by SER (p > 0.05, Supplementary Tables S1–S4)
The current study showed that the minimal bactericidal concentrations (MBCs)/minimal inhibitory concentrations (MICs) ratio is ≤2, with the exception of H. pylori 7143 strain, for which it was equal to 4
Summary
The presence of spiral microorganisms inhabiting the gastric mucosa was noticed more than 100 years ago, but the lack of a way to isolate these microorganisms using standard culture methods probably reduced interest in this topic [1]. A key moment was the isolation of a spiral, Gram-negative rod, known today as Helicobacter pylori, which was obtained from gastric biopsies by Barry Marshall and Robin Warren in 1983. Subsequent progression in research on H. pylori has shown the involvement of this bacterium in the development of gastric diseases, including gastritis, gastric and duodenal ulcers, gastric cancers, and gastric mucosa-associated lymphoid tissue lymphomas [3]. The detection of H. pylori in patients, regardless of the presence of symptoms, is an indication for antibiotic therapy. This recommendation was administered during three independent consensus conferences in Brazil, Kyoto, and Maastricht [4,5,6]
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