Pathogenic mechanisms of chronic infections

Staphylococcus aureus (S. aureus) is a very versatile opportunistic human pathogen. Besides an asymptomatic colonisation of humans, it can cause a multiplicity of infections, which vary in severity. By investigating a possible connection between certain pathologies and bacterial phenotypes, general and specific infection patterns are supposed to be identified. Therefore, a strain collection based on four S. aureus induced infections and colonisation, with 10-12 strains per group, was established. Staphylococcal strains were isolated from sepsis, haematogenous osteomyelitis, prosthesis infections and from the nasal area of healthy people. Together with the acquisition of selected patient characteristics, strains were characterised genotypically and by their phenotypic expression of virulence factors. Moreover, the bacterial interaction with osteoblasts was analysed in functional assays that determined invasiveness and cytotoxicity. Selected bacterial isolates were examined for their ability to persist within bone cells and their performance in a murine sepsis / osteomyelitis model. Against expectations, a pathology specific bacterial pattern could not be identified. The analysis of patient characteristics indicates an important role of the hosts health status for the course of the infection. However, in all isolate groups, the values of the individual strains were distributed in a broad spectrum. The application of correlation analysis helped to identify two distinct infection strategies. It revealed the opposing nature of invasion and cytotoxicity as low cytotoxic strains tend to be high invasive and vice versa. Even though S. aureus was shown to be able to invade, persist within cells, and to form small colony variants (SCVs) independently of its cytotoxicity, low cytotoxic strains exhibited higher persistence rates. This observation can possibly be attributed to the decreased production of toxins and the reduced activation of the host immune system.


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