Anuforom, Olachi Nnediogo (2015). The role of the immune response in the effectiveness of antibiotic treatment for antibiotic susceptible and antibiotic resistant bacteria. University of Birmingham. Ph.D.
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Anuforom15PhD.pdf
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Abstract
The increasing spread of antimicrobial resistant bacteria and the decline in the development of novel antibiotics have incited exploration of other avenues for antimicrobial therapy, such as the use of antibiotics that enhance the host’s defenses to infection. This study explores the influence of antibiotics on the innate immune responses to bacteria. The aims were to investigate antibiotic effects on bacterial viability, innate immune cells in response to bacteria and interactions between bacteria and the host. Five exemplar antibiotics at maximum serum concentration (C\(_m\)\(_a\)\(_x\)) and minimum inhibitory concentrations (MIC) were tested. \(Salmonella\) Typhimurium SL1344 was chosen as the model pathogen.
Following incubation of SL1344 with C\(_m\)\(_a\)\(_x\) concentrations of ceftriaxone bacterial viability was undetectable. When SL1344 was incubated with ceftriaxone and ciprofloxacin treated neutrophils, there was reduced bacterial viability. Ciprofloxacin pre-treated neutrophils had reduced ability to phagocytose bacteria, while oxidative burst was increased following exposure to ceftriaxone. Adhesion of SL1344 to J774 macrophages pre-exposed to both concentrations of ciprofloxacin and ceftriaxone was increased, but only C\(_m\)\(_a\)\(_x\) of azithromycin and streptomycin. Expression of IL-1β and TNFα mRNA was greater in SL1344 infected macrophages pre-exposed to ciprofloxacin or ceftriaxone, than in macrophages exposed to antibiotics alone or SL1344 alone.
In conclusion, it was found that clinical relevant concentrations of certain antibiotics enhance the response of immune cells and their interaction with bacteria, by increasing phagocytosis and killing in neutrophils, increasing bacterial adhesion to macrophages and increased cytokine production. These immunomodulatory potentials of antibiotics can be harnessed and exploited for broader therapeutic use.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
| School or Department: | School of Immunity and Infection | |||||||||
| Funders: | None/not applicable | |||||||||
| Subjects: | Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology |
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| URI: | http://etheses.bham.ac.uk/id/eprint/5955 |
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