Abstract
Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, and from patients with endoprosthesis infection, hematogenous osteomyelitis, and sepsis. All strains were characterized by genotypic analysis, and by the expression of virulence factors. The host–pathogen interaction was studied through several functional assays in osteoblast cultures. Additionally, selected strains were tested in a murine sepsis/osteomyelitis model. We did not find characteristic bacterial features for the defined infection types; rather, a wide range in all strain collections regarding cytotoxicity and invasiveness was observed. Interestingly, all strains were able to persist and to form small colony variants (SCVs). However, the low-cytotoxicity strains survived in higher numbers, and were less efficiently cleared by the host than the highly cytotoxic strains. In summary, our results indicate that not only destructive, but also low-cytotoxicity strains are able to induce infections. The low-cytotoxicity strains can successfully survive, and are less efficiently cleared from the host than the highly cytotoxic strains, which represent a source for chronic infections. The understanding of this interplay/evolution between the host and the pathogen during infection, with specific attention towards low-cytotoxicity isolates, will help to optimize treatment strategies for invasive and therapy-refractory infection courses.
Highlights
Staphylococcus aureus is a very versatile pathogen that often colonizes the epithelial surfaces of healthy individuals [1,2]; but it is the most common pathogen of the bloodstream, surgical side, and bone infections, which are often complicated, with several sites of metastatic foci, and the development of chronic infections [3]
S. aureus is a versatile microorganism that causes a diverse array of infections
For different pathologies connected to S. aureus a controversial link between virulence and clinical outcome has been discussed [16,24,25]
Summary
Staphylococcus aureus is a very versatile pathogen that often colonizes the epithelial surfaces of healthy individuals [1,2]; but it is the most common pathogen of the bloodstream, surgical side, and bone infections, which are often complicated, with several sites of metastatic foci, and the development of chronic infections [3]. The diversity of infections that are associated with S. aureus is due to the multiple virulence factors and its adaptation to different environments in the human host. This particular adaptation facilitates the bacteria’s survival in the host, and their evasion of the host immune system [5]. S. aureus displays defined virulence factors, including adhesive surface proteins (adhesins) and toxic compounds that act in concert to destroy the host tissue and to resist the host defense system. The bacteria need to survive within the bloodstream, to defend against immune cells. After the infection is settled, the bacteria invade and adapt to the host tissue for persistence and escape from the host immune system, which is mainly mediated by the upregulation of
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