CORTICOSTEROID-INDUCED EXPRESSION OF MICROBIAL VIRULENCE CAN ENHANCE THE DEVELOPMENT OF HOST INFECTIOUS DISEASE

Abstract

Corticosteroids regulate a number of physiological processes and are synthetic analogs of the natural steroid hormones produced by the adrenal cortex. As drugs, corticosteroids are non-inflammatory and are used for the treatment of plethora of conditions which include arthritis, kidney, skin, lungs or thyroid disorders, for the treatment and relief of symptoms of allergies and symptoms of some gastrointestinal disorders. In addition, glucocorticoids can regulate the effects of inflammatory disorders, including sepsis, autoimmune diseases, and allergies. These conditions are potentially fatal. Consequently, this drug class is among the most commonly prescribed globally. One representative of corticosteroid class of drugs is dexamethasone which is used to treat allergies, adrenal problems, arthritis, asthma, diseases of blood or bone marrow, inflammation, kidney diseases, different types of skin conditions, and episodes of multiple sclerosis. Virulence factors help bacteria colonize the host at the level of the cell. In their nature, these factors are secretory, associated with the membrane or present in the cytosol. Secretory factors allow bacterium to circumvent the host immune response, while membrane factors aid bacterium in adhesion to the host cell. Finally, cytosol factors help bacteria adapt metabolically, physiologically, and morphologically to their changing environment. One such factor is aspartyl proteinase, a protein that degrades other proteins and is a virulence factor in many pathogens playing a role in the host invasion process. Another important virulence factor is the ability to form biofilms, which can render bacteria resistant to antimicrobials. Despite the widespread use of corticosteroids, including dexamethasone, little is known about their possible influence on the expression of virulence factors such as aspartyl proteinase. If such a connection is to exist the use of corticosteroids could elicit pathogenesis in certain microbes. In the here-presented study we wanted to investigate the effects of dexamethasone on the growth, expression of aspartyl proteinase and biofilm formation in three E. coli strains that were previously isolated from patients suffering from urinary tract infection. To this aim, we amended the growth media with 0.5 mg/mL dexamethasone. Bacterial growth was measured over the period of 24 hours and the effect of dexamethasone was established at different time points. Administration of 0.5 mg/mL glucocorticoid drug dexamethasone did not significantly affect bacterial growth. However, it resulted in an increase in concentration of secreted E. coli virulence factor aspartyl proteinase, which increased up to 2.6-fold for some E. coli strains. In addition, we noted the increased biofilm formation in to three out of four studied strains. This study indicates dexamethasone as a possible trigger molecule for the expression of virulence factor aspartyl proteinase in E. coli.