In vitro activity of sub-minimum inhibitor concentrationsof erythromycin on Bordetella pertussis tohama – I

Whooping cough (pertussis) is an acute respiratory disease caused by Bordetella pertussis that leads to death, especially in infants. Although it is known as a childhood disease, it is also common in adolescents and adults. Vaccination campaigns against pertussis have reduced the number of cases over time. However, despite widespread vaccination, the number of cases remains high today. Changes in the genes of the bacterium's virulence factors, in particular, have contributed significantly to the increase in the number of cases over time by reducing the effectiveness of vaccines. Macrolide group antibiotics are widely used in the treatment of pertussis. It is known that bacteria develop resistance to antibiotics when high doses of antibiotics are used and that the use of low doses can lead to changes in the expression of virulence genes of the bacteria in question. However, there are no detailed studies on the effects of sub minimum inhibitory concentrations (sub-MIC) of antibiotics on gene expression and virulence of B. pertussis. In this study, the minimum inhibitory concentration (MIC) of erythromycin was determined and the effects of sub-MIC concentrations on growth capacity, biofilm-forming capacity, pertussis toxin (ptxS1), and pertactin (prn) gene expression of B. pertussis were investigated. It was found that 1/2, 1/4, and 1/8 MIC doses of erythromycin significantly inhibited the growth of B. pertussis. The growth capacity of B. pertussis was significantly decreased at 1/16, 1/32, and 1/64 sub-MIC concentrations of erythromycin compared to the control. There was no significant growth at 1/2, 1/4, and 1/8MIC doses of erythromycin. Therefore, biofilm, and gene expression analyses were continued at 1/16, 1/32, and 1/64MIC concentrations. The ability of B. pertussis to form biofilms in sub-MICs decreased significantly in parallel with the erythromycin dose. Expression levels of ptxS1 and prn genes were also statistically significantly decreased at sub-MIC concentrations compared with controls. Interestingly, the expression levels of ptxS1 and prn were higher at 1/32 sub-MIC then at than the other sub-MICs. However, there is no statistically significant difference between them. This thesis is the first study to investigate the effects of sub-MICs of antibiotics on B. pertussis cells, and these results are important from a scientific point of wiev. Expression levels of ptxS1 and prn genes were also statistically significantly decreased at sub-MIC concentrations compared with controls.