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• W2941294170 abstract "There is increasing evidence that subinhibitory concentrations of antibiotics interfere with host-pathogen interactions. It has been shown that the expression of several virulence-associated genes of Staphylococcus (S.) aureus may be affected in vitro by low concentrations of various antibiotics, especially those that inhibit protein biosynthesis. The aim of this study was to investigate the influence of subinhibitory concentrations of florfenicol (Ff), a fluorinated chloramphenicol derivative, on growth, morphology and viability [Chapter 2] and on virulence properties [Chapters 3-5] of S. aureus. In the first part of this study [Chapter 2], it was shown that S. aureus strain Newman, when grown in the presence of a high subinhibitory concentration of Ff, exhibited a distinct growth retardation and a significant increase in cell wall thickness. The latter effect might result in a compression of the protoplast with subsequent disruption of single staphylococcal cells. Electron microscopy revealed approximately 20% of the S. aureus Newman cells to be disrupted. However, a bactericidal activity was not recorded at this concentration. Since the ability of S. aureus to adhere to host tissues is essential for the colonization and further establishment of the infection, the second part of this study [Chapters 3-5] focussed on adherence to epithelial cells as the initial step of staphylococcal infections. It was demonstrated that Ff-susceptible and Ff-resistant S. aureus strain Newman exhibited increased adherence to and invasion of HEp-2 cells, when grown in the presence of the strain-specific ½ the minimum inhibitory concentration (MIC) of Ff. Interactions with the adherence-mediating ligands fibronectin and fibrinogen were shown to play an important role in this process. Northern slot blot analysis revealed that the amounts of transcripts of the genes fnbA, fnbB, coa, emp and eap, coding for specific adhesins that can bind fibronectin and/or fibrinogen, were increased in the presence of ½ MIC of Ff. Under the same conditions expression of the type 5 capsular polysaccharide (CP5), that can mask surface proteins involved in adherence, was distinctly decreased. Since it is known that global regulatory systems can modulate the expression of adhesins, their role in the increased adherence was investigated by including three mutants with functionally inactive global regulator systems agr, sar, or sae. A comparison of the S. aureus Newman and its mutants indicated that the Ff-dependent increased adherence to fibronectin- or fibrinogen-coated microtiter plates and to HEp-2 cells is a process in which the sae system, but not the agr or sar system, might be involved. In contrast to components of the agr or sar system, expression of saeRS was increased, suggesting a potential sae-directed decrease in the expression of CP5 and increase in expression of specific adhesins, respectively. Analysis of RNA stability revealed that the increased amount of transcripts coding for the global regulator sae, and also for specific adhesins, in the presence of Ff was, at least partially, due to a stabilization of the respective mRNAs. These results allow to hypothesize that stabilization of transcripts coding for the global regulator sae and a sae-directed decreased expression of CP5, as well as increased expression of specific adhesins, and stabilization of the mRNA coding for these adhesins may contribute synergistically to the Ff-induced adherence of S. aureus. To differentiate a Ff-specific effect from a general stress response, that may be produced by antibiotics that inhibit bacterial protein biosynthesis, it was tested whether a high subinhibitory concentration of clindamycin (Cli) may yield the same results. However in contrast to Ff, no significant change in adherence properties was detectable when S. aureus Newman was treated with ½ MIC of Cli. In conclusion, the results of this study showed that a subinhibitory concentration of Ff may have significant effects on physiology and virulence properties of S. aureus. Consequently, this could substantially influence the management of S. aureus infections." @default.
• W2941294170 created "2019-05-03" @default.
• W2941294170 creator A5067787792 @default.
• W2941294170 date "2004-01-01" @default.
• W2941294170 modified "2023-09-23" @default.
• W2941294170 title "Florfenicol-dependent modulation of staphylococcal virulence properties" @default.
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