Effects of Erdosteine and Its Metabolites on Bacterial Adhesiveness

Abstract

Summary Erdosteine (CAS 84611-23-4) is administered as a mucolytic drug in patients with pulmonary disorders who suffer from a thickening of bronchial mucus with altered physico-chemical characteristics. Erdosteine itself does not have a free thiol group but its metabolization produces active metabolites with a -SH group that is capable of breaking disulfide bonds of mucins and improving the mucociliary clearance of the airways, and thus reproducing the effects of the class of mucoactive drugs having a thiol group. It has also been reported that muco-active drugs with this group reduce bacterial adhesiveness to human mucosal cells. The aim of this study was to investigate whether erdosteine and its SH-metabolites are capable of interfering with bacterial adhesiveness. Metabolite I significantly reduces both S. aureus and E. coli adhesiveness to human mucosal epithelial cells at concentrations of 2.5, 5 and 10 &ml. The same concentrations of erdosteine, metabolite II, metabolite III and N-acetylcysteine (as a control drug) were devoid of such activity, whereas the results of hemagglutination and hydrophobicity assays showed that the behaviour of metabolite I overlapped that of bacterial adhesiveness, thus indicating that interference takes place at a fimbrial level. This is confirmed by the fact that the incubation of human buccal cells with drugs does not reduce the adhesiveness of untreated bacteria. The presence of this additional activity in a mucoactive drug is useful because bacteria not only adhere to epithelial cells but also to tracheobronchial secretions.

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

“…Similarly, less risk for exacerbations of chronic bronchitis or chronic obstructive pulmonary disease (COPD) has been recently confirmed in patients taking mucolytics probably due to reduced mucus viscosity making it easier to expectorate (Poole et al, 2019). Mucolytics provide also additional direct cilio-stimulatory and bronchodilator effects without impact on the cough sensitivity, anti-inflammatory (Pappova et al, 2017;Frañováet al, 2019), antioxidant (Miyake et al, 1999) or immunomodulatory properties, in addition to the ability to reduce bacterial adhesiveness (Braga et al, 1999, Pappová et al, 2018.…”

Understanding the Role of the Antioxidant Drug Erdosteine and Its Active Metabolite on Staphylococcus aureus Methicillin Resistant Biofilm Formation

“…The effect of Er and Met I on bacterial adhesion, mature biofilm and biofilm dispersal, by setting up a laboratory-scale model system simulating conditions encountered in vivo. Pharmacological concentrations close to the plasma peak value obtained after oral administration and previously used by Braga et al [ 26 ] has been used. Additionally, the impact of ROS on biofilm formation was measured.…”

“…Scientific evidence showed that thiol-based drugs can reduce bacterial adhesion to the respiratory epithelial cell surface, inhibiting biofilm formation and improving the efficacy of antibiotic therapy [ 25 ]. It has been reported that 2.5, 5 and 10 mg/L of Met I acts at a fimbrial level, by reducing both S. aureus and Escherichia coli adhesiveness to human mucosal epithelial cells that is the first step in the development of respiratory tract infections [ 26 ]. Braga et al [ 26 ] suggested that Er and Met I exert their anti-adhesion activity by inducing a stereochemical conformational change of the pilin molecules that impedes their binding to the receptors of human cells.…”

“…It has been reported that 2.5, 5 and 10 mg/L of Met I acts at a fimbrial level, by reducing both S. aureus and Escherichia coli adhesiveness to human mucosal epithelial cells that is the first step in the development of respiratory tract infections [ 26 ]. Braga et al [ 26 ] suggested that Er and Met I exert their anti-adhesion activity by inducing a stereochemical conformational change of the pilin molecules that impedes their binding to the receptors of human cells. However, they neither verified whether the resulting data came from a biocidal activity of the drug rather than a real anti-adhesion effect, nor gave proofs about the drug’s activity on the pilin molecules.…”

Mucolytics/antioxidants: When Are They Useful?

“…The therapeutic benefit of thiols is not limited to their mucolytic effect. Several preclinical studies and data collected from humans have shown the ability of these agents to interfere with inflammatory pathways 5,9,10 , modulate human bronchial tone 11 , reduce bacterial adhesion to the surface of respiratory epithelial cells [12][13][14] , and inhibit biofilm formation or cause their rupture, thus improving the efficacy of antibiotic therapy 12 . However, not all of these additional actions have been documented for each of the three thiols 2 .…”