Applications of traditional Chinese medicines: bacterial biofilms as a target

Abstract

Chinese Herbal Medicines (CHM) are of significant importance for human health care in China and have a profound cultural and philosophical background described in the Traditional Chinese Medicine (TCM) theories. The main objective of TCM is to maintain or restore the balance of the body as a whole (homeostasis), rather than to treat an individual symptom of functional defect. These different objectives create significance differences in the understanding and interpretation of disease conditions. For example, TCM does not describe bacteria as individual pathogens but treats bacterial infections with herbs, selected for their so-called heat-clearing properties (heat, i.e. elevated temperature is the common symptom of local as well as systemic infections (fever). Heat-clearing properties (the heat-Zheng) encompass antimicrobial, anti-inflammatory and tissue repairing effects and herbal extract combining all these properties are selected for the treatment of patients with bacterial infections. This is in contrast to the Western medicine applying single defined molecules such as individual antibiotics as primary remedies in the treatment of bacterial infections, and in some cases combines these with anti-inflammatory effect to alleviate the symptoms of a bacterial infection

Recently the use of antibiotics is challenged by the world-wide emergence of antimicrobial resistance, resulting in apparent therapy resistance and the progression of infections into chronic diseases. One of the mechanisms that is involved in therapy resistance, is the formation of biofilms, which can be described as a sessile community of bacteria surrounded by a self-produced extracellular matrix. In the biofilm mode, bacteria are rather insensitive to most antibiotics, as they are not only protected by the polysaccharide extracellular matrix, but also because of the achieve in the biofilm a dormant stage, which makes many antibiotics interfering with cell wall biosynthesis or bacterial protein synthesis ineffective. Moreover, biofilms are not detected by the immune cells and this phenomenon also favours the development of chronic infections. Previous investigations had indicated already that various herbal products might have antibacterial as well as anti-biofilms properties by interfering with bacterial signalling (quorum sensing) and/or by suppressing bacterial genes encoding factors that determine biofilm formation and maturation.

Hence it was the aim of the experimental work described in this thesis to identify out of the group of heat-clearing CHM, with a proven beneficial effect in the management of bacterial infections, those plant extracts that have antibacterial and anti-biofilm properties. For this approach, Staphylococcus epidermidis was used as model for Gram-positive bacteria that commonly form biofilms. In line with the heat-Zheng theory, the anti-inflammatory and anti-oxidant properties of CHM were tested as well. Moreover, to assess the effect of environmental stress factors on biofilm formation, the same bacterial strains of S. epidermidis were used to assess the effect of heavy metals, including cadmium, lead, nickel, manganese and mercury on biofilm formation.