Studies on the risk assessment of Listeria monocytogenes

Humans are frequently exposed to Listeria monocytogenes, and high numbers may be ingested during consumption of certain types of food. However, epidemiological investigations show that listeriosis is a rare disease. Risk assessment studies using an animal mouse model indicate that almost all L. monocytogenes serovars present in food have clear virulent properties. The intravenous dose causing infection in 50% (IV ID50) of mice not previously exposed to L. monocytogenes (nonprotected mice) was 1.8 log10 units. For mice previously exposed to L, monocytogenes (immunologically protected mice), the IV ID50 was 5.6 log10 units. The ID50 of orally exposed nonprotected mice amounted to 6.5 log10 units, and no significant effects of type of food (water/milk) and storage time at 5°C (milk) were observed. The oral ID50 of immunologically protected mice was >9.0 log10 units. Furthermore, there was approximately 1-2 log10 difference between the ID10 and the lethal dose causing death in 50% (LD50). The results show that both the intestinal barrier and the specific immune defense mechanism are highly effective in preventing infection of mice orally exposed to L. monocytogenes. Delaying the immune defense had no effect on the protective activity of the intestinal barrier, indicating that these protective mechanisms operate independently. The risk assessment results obtained in the mouse model support the epidemiological finding that listeriosis is a rare disease in humans, despite frequent exposure to the organism

PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus

The Staphylococcus aureus genome encodes three ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of PerR, we inactivated the gene by allelic replacement using a kanamycin cassette, creating strain MJH001 (perR). PerR was found to control transcription of the genes encoding the oxidative stress resistance proteins catalase (KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin comigratory protein (Bcp), and thioredoxin reductase (TrxB). Furthermore, PerR regulates transcription of the genes encoding the iron storage proteins ferritin (Ftn) and the ferritin-like Dps homologue, MrgA. Transcription of perR was autoregulated, and PerR repressed transcription of the iron homeostasis regulator Fur, which is a positive regulator of catalase expression. PerR functions as a manganese-dependent, transcriptional repressor of the identified regulon. Elevated iron concentrations produced induction of the PerR regulon. PerR may act as a peroxide sensor, since addition of external hydrogen peroxide to 8325-4 (wild type) resulted in increased transcription of most of the PerR regulon, except for fur and perR itself. The PerR-regulated katA gene encodes the sole catalase of S. aureus, which is an important starvation survival determinant but is surprisingly not required for pathogenicity in a murine skin abscess model of infection. In contrast, PerR is not necessary for starvation survival but is required for full virulence (P < 0.005) in this model of infection. PerR of S. aureus may act as a redox sentinel protein during infection, analogous to the in vitro activities of OxyR and PerR of Escherichia coli and Bacillus subtilis, respectively. However, it differs in its response to the metal balance within the cell and has the added capability of regulating iron uptake and storage