Selection of resistant bacteria at very low antibiotic concentrations.

The widespread use of antibiotics is selecting for a variety of resistance mechanisms that seriously challenge our ability to treat bacterial infections. Resistant bacteria can be selected at the high concentrations of antibiotics used therapeutically, but what role the much lower antibiotic concentrations present in many environments plays in selection remains largely unclear. Here we show using highly sensitive competition experiments that selection of resistant bacteria occurs at extremely low antibiotic concentrations. Thus, for three clinically important antibiotics, drug concentrations up to several hundred-fold below the minimal inhibitory concentration of susceptible bacteria could enrich for resistant bacteria, even when present at a very low initial fraction. We also show that de novo mutants can be selected at sub-MIC concentrations of antibiotics, and we provide a mathematical model predicting how rapidly such mutants would take over in a susceptible population. These results add another dimension to the evolution of resistance and suggest that the low antibiotic concentrations found in many natural environments are important for enrichment and maintenance of resistance in bacterial populations.

Expression of interferon gamma in the brain of cats with natural Borna disease virus infection.

Borna disease virus (BDV) is a neurotropic, negative-stranded RNA virus, which causes a non-suppurative meningoencephalomyelitis in a wide range of animals. In cats, BDV infection leads to staggering disease. In spite of a vigorous immune response the virus persists in the central nervous system (CNS) in both experimentally and naturally infected animals. Since the CNS is vulnerable to cytotoxic effects mediated via NK-cells and cytotoxic T-cells, other non-cytolytic mechanisms such as the interferon (IFN) system is favourable for viral clearance. In this study, IFN-γ expression in the brain of cats with clinical signs of staggering disease (N=12) was compared to the expression in cats with no signs of this disease (N=7) by quantitative RT-PCR. The IFN-γ expression was normalised against the expression of three reference genes (HPRT, RPS7, YWHAZ). Cats with staggering disease had significantly higher expression of IFN-γ compared to the control cats (p-value ≤ 0.001). There was no significant difference of the IFN-γ expression in BDV-positive (N=7) and -negative (N=5) cats having clinical signs of staggering disease. However, as BDV-RNA still could be detected, despite an intense IFN-γ expression, BDV needs to have mechanisms to evade this antiviral immune response of the host, to be able to persist.