A strain-independent method to induce progressive and lethal pneumococcal pneumonia in neutropenic mice

Abstract

BackgroundExperimental models of pneumonia with penicillin non-susceptible Streptococcus pneumoniae (PNSSP) are hard to reproduce because the majority of strains with clinical relevance (like serotypes 6B, 9 V and 19 F) have low murine virulence. By optimization of culture and inoculum conditions of PNSSP (using porcine mucin), our aim was to develop a suitable, reliable and reproducible pneumonia mouse model for anti-infective pharmacology research.ResultsSeven PNSSP strains, including serotypes 6B, 9 V, 14 and 19 F were included. Strain INS-E611 displayed the highest murine virulence and was chosen to validate the lung model. Nose-instilled pneumococci grew between 2.1 and 2.5 log10 CFU/g of lung in 24 hours when an optimized culture of bacterial cells was used, but animals were all alive and recovered of infection after 36 h. In contrast, inoculum supplementation with mucin led to 100% mortality related to a successful lung infection confirmed by histopathology. These findings were reproduced with all seven PNSSP strains in neutropenic mice. Immunocompetent animals cleared all strains spontaneously.ConclusionsThis pneumonia model produces a progressive and uniformly fatal lung infection with diverse serotypes of PNSSP independently of their intrinsic murine virulence.

Mucins as multifunctional building blocks of biomaterials

“…Mucinous tumors also produce a physical mucin barrier that shields tumors from the immune system and limits cell-cell interactions that facilitate metastasis. 74 Interestingly, it was standard procedure from the 1930s up to the 1970s and even occasionally more recently, 75 to co-administer mucins along with pathogenic bacteria, 76,77 viruses, 78 and fungi 79 in small animal models, such as mice, to lower their resistance and develop pathologies. Mucins were also found to prolong the survival of bacterial cultures.…”

Demonstration of Therapeutic Equivalence of Fluconazole Generic Products in the Neutropenic Mouse Model of Disseminated Candidiasis

“…To determine the lethality of the model in untreated animals, an additional group of 3 mice was followed for 120 h after infection, checking the animals every 24 h for survival. Animals were euthanized by cervical dislocation under isoflurane sedation when any of these criteria was fulfilled: (a) inability to obtain feed or water, or (b) no response to gentle stimuli or moribund state [ 25 ]. Animals were bred and maintained in the pathogen-free vivarium of the University of Antioquia; transfer to the experimental area occurred 24 h before starting immunosuppression.…”