Innate refractoriness of the Lewis rat to toxoplasmosis is a dominant trait that is intrinsic to bone marrow-derived cells.

Toxoplasmosis is a ubiquitous parasitic infection causing a wide spectrum of diseases. It is usually asymptomatic but can lead to severe ocular and neurological disorders. Among the small-animal models available to study factors that determine susceptibility to toxoplasmosis, the rat appears to be rather similar to humans, particularly in terms of resistance to acute infection. Here, we demonstrate that the Lewis (LEW) rat strain displays an unexpected refractoriness to Toxoplasma infection. Complete resistance was assessed by both negative anti-Toxoplasma serology and lack of detection of the parasite during the course of infection. In this model, sex, age, major histocompatibility complex, and inoculum size had no effect on resistance. Interestingly, progeny from F(1) hybrid crosses between Fischer (F344) or Brown Norway susceptible rats and LEW resistant rats were also fully resistant, showing a dominant effect of the gene or set of genes. Furthermore, resistance of the LEW rat was shown to be dependent on hematopoietic cells and partially abrogated by neutralization of endogenous gamma interferon. To our knowledge, this is the first observation of a rodent strain that is refractory to Toxoplasma infection. This model is therefore an attractive and powerful tool to dissect host genetic factors involved in susceptibility to toxoplasmosis.

Potential of beta-galactosidase-expressing Toxoplasma gondii for in situ localization and observation of rare stages of the parasite life cycle.

A cyst-forming strain of Toxoplasma gondii was transfected with the Escherichia coli LacZ gene and expressed beta-galactosidase constitutively. This strain has been used to localize and analyze the early stages of development and reactivation of T. gondii in mice. The chromogenic detection of the enzyme allows an easy detection of the parasites after light fixation and therefore allows a submacroscopic analysis of tissue distribution within the organism. Also, it allows further embedding and retrieval of rare stages for electron microscopic observation. that detect the presence of the parasite and initiate the response, and (2) the early stages of reactivation, when the cysts are supposed to break open and release the infectious bradyzoïtes. We have taken advantage of the possibility of detecting the enzymatic activity of beta-galactosidase (beta-gal) in transfected parasites to show that one could perform a semi-macroscopic detection and that this was compatible with further analysis by histological or electron microscopic techniques, being therefore able to detect the rare events and then to analyze them further with more refined morphological techniques.

Bactericidal activity of three beta-lactams alone or in combination with a beta-lactamase inhibitor and two aminoglycosides against Klebsiella pneumoniae harboring extended-spectrum beta-lactamases.

OBJECTIVE: To study the bactericidal activity of beta-lactam antibiotics (imipenem, cefepime, cefpirome) alone or in combination with a beta-lactamase inhibitor (sulbactam) in the presence or absence of aminoglycoside (amikacin or isepamicin) against Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases (ESBLs). METHODS: We characterized 10 strains by means of analytic isoelectric focusing and pulsed-field gel electrophoresis. The ESBLs produced by these strains were derived from either TEM (TEM-1, TEM-2) or SHV-1. The killing-curve method was used for this bacterial investigation. Bacteria (final inoculum 5x105 CFU/mL) were incubated with antibiotics at clinical concentrations obtained in vivo. RESULTS: All the combinations with cefepime or cefpirome + sulbactam were bactericidal, with a 4 log10 decrease being obtained within 6 h without regrowth at 24 h, whereas imipenem alone, and combinations, gave a bactericidal effect within 6 h. The two cephalosporins alone decreased the inoculum of 4 log10 at 6 h but regrowth was observed at 24 h. When the aminoglycoside was added, this bactericidal effect was obtained within 3 h with amikacin and within 1 h with isepamicin. CONCLUSIONS: Cefepime + sulbactam or cefpirome + sulbactam may be an alternative to imipenem for the treatment of patients with ESBL-producing K. pneumoniae. Aminoglycosides are often associated in nosocomial infections due to ESBL-producing K. pneumoniae: isepamicin acted faster than amikacin, but both worked well. To conclude, it may be prudent to avoid extended-spectrum cephalosporins as single agent when treating serious infections due to ESBL-producing K. pneumoniae. Addition of a beta-lactamase inhibitor such as sulbactam +/- aminoglycoside is advisable to avoid failure of treatment.