Non-antibiotics, Efflux Pumps and Drug Resistance of Gram-negative Rods

Non-antibiotic medicinal products consist of drugs with diverse activity against bacteria. Many non-antibiotics demonstrate direct anti-bacterial activity against Gram-positive cocci. The activity observed against Gram-negative rods is much lower and non-antibiotics primarily from the following groups: non-steroidal anti-inflammatory drugs, cardiovascular and antidepressant medicinal products demonstrate this activity. It has been shown that the low activity of some non-antibiotics or the absence of activity against Gram-negative rods is related, among other things, to the extrusion of these compounds from bacterial cells by multi-drug resistance efflux pumps. Substrates for the resistance-nodulation-division efflux systems include the following non-antibiotics: salicylate, diclofenac, ibuprofen, mefenamic acid, naproxen, amitriptyline, alendronate sodium, nicergoline, and ticlopidine. In addition, interactions between non-antibiotics and multi-drug resistance efflux pumps have been observed. It has also been revealed that depending on the concentration, salicylate induces expression of multi-drug resistance efflux pumps in Escherichia coli, Salmonella enterica subsp. enterica serotype Typhimurium, and Burkholderia cenocepacia. However, salicylate does not affect the expression of the resistance-nodulation-division efflux systems in Stenotrophomonas maltophilia and Acinetobacter baumannii. Most importantly, there were no effects of medicinal products containing some non-antibiotic active substances, except salicylate, as substrates of multi-drug resistance efflux pumps, on the induction of Gram-negative rod resistance to quinolones

The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria

The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO4. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide) was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100–800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species

Glycoprotein Hypersecretion Alters the Cell Wall in Trichoderma reesei Strains Expressing the Saccharomyces cerevisiae Dolichylphosphate Mannose Synthase Gene

Expression of the Saccharomyces cerevisiae DPM1 gene (coding for dolichylphosphate mannose synthase) in Trichoderma reesei (Hypocrea jecorina) increases the intensity of protein glycosylation and secretion and causes ultrastructural changes in the fungal cell wall. In the present work, we undertook further biochemical and morphological characterization of the DPM1-expressing T. reesei strains. We established that the carbohydrate composition of the fungal cell wall was altered with an increased amount of N-acetylglucosamine, suggesting an increase in chitin content. Calcofluor white staining followed by fluorescence microscopy indicated changes in chitin distribution. Moreover, we also observed a decreased concentration of mannose and alkali-soluble β-(1,6) glucan. A comparison of protein secretion from protoplasts with that from mycelia showed that the cell wall created a barrier for secretion in the DPM1 transformants. We also discuss the relationships between the observed changes in the cell wall, increased protein glycosylation, and the greater secretory capacity of T. reesei strains expressing the yeast DPM1 gene

Antioxidant and Antibacterial Activity of Extracts from Selected Plant Material

Plants are a valuable source of biologically active molecules, mainly phenolic compounds. In the present study, the total phenolic content (TPC), DPPH· and ABTS+ scavenging activity as well as ferric reducing ability (FRAP) of aqueous ethanolic (70%) extracts of Cistus incanus L. and Asarum europaeum L. herb, Geum urbanum L. rhizome, Angelica archangelica L. root, white mulberry (Morus alba L.), lemon balm (Melisa officinalis L.), red raspberry (Rubus idaeus L.) and Betula pendula Roth. leaves were determined. In addition, the phenolic profiles of the studied plant extracts and antibacterial activity have been investigated. The extracts from C. incanus and G. urbanum demonstrated the highest TPC and antioxidant capacity, while the extracts from A. archangelica and white mulberry were characterized by the lowest values. A remarkable correlation was also found between the TPC and antioxidant activity of the examined extracts. HPLC analysis showed that the studied extracts were sources of both phenolic acids and flavonoids. More flavonoids than phenolic acids were identified in the extracts of C. incanus, M. alba, R. idaeus and B. pendula compared to the other extracts tested. Not all extracts showed a significant impact on the growth of the tested bacterial strains. Escherichia coli was the most sensitive strain to lemon balm extract (MIC, 0.125 mg/mL), whereas the strains of Acinetobacter baumannii and Bordetella bronchiseptica were sensitive to the G. urbanum extract (MIC, 0.125 mg/mL). Among Gram-positive bacteria, Enterococcus faecalis was the most sensitive to G. urbanum extract. In turn, Staphylococcus aureus and Staphylococcus epidermidis were sensitive to the extracts from C. incanus herb (MIC, 0.125 mg/mL), red raspberry (MIC, 0.125 mg/mL) and lemon balm leaves (MIC. 0.25 mg/mL). Based on the obtained results, the applicability of the studied plant extracts as additives to food and cosmetic products may be considered in the future