Development of a non-invasive murine infection model for acute otitis media

Autor: Kim Stol, Hester J. Bootsma, Peter W. M. Hermans, Kees Graamans, S. van den Berg, W. A. M. Blokx, E. L. G. M. Tonnaer, S. van Selm
Přispěvatelé: Medical Microbiology & Infectious Diseases
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Time Factors
Genetics and epigenetic pathways of disease [NCMLS 6]
medicine.medical_treatment
Interleukin-1beta
medicine.disease_cause
Pathogenesis
Mice
Genomic disorders and inherited multi-system disorders Auto-immunity
transplantation and immunotherapy [IGMD 3]
Nasopharynx
Mice
Inbred BALB C
Virulence
Peptidylprolyl Isomerase
Pathogenesis and modulation of inflammation [N4i 1]
Cytokine
Streptococcus pneumoniae
Child
Preschool
Acute Disease
Female
medicine.symptom
Functional Neurogenomics [DCN 2]
Infection and autoimmunity [NCMLS 1]
DNA
Bacterial
Ear
Middle
Biology
Microbiology
Auto-immunity
transplantation and immunotherapy [N4i 4]
Pneumococcal Infections
Bacterial Proteins
In vivo
Translational research [ONCOL 3]
medicine
Pressure
Animals
Humans
DNA Primers
Base Sequence
Tumor Necrosis Factor-alpha
Infant
Streptococcaceae
biology.organism_classification
Rats
Disease Models
Animal
Otitis Media
Otitis
Genes
Bacterial
Immunology
Mutation
biology.protein
Protein A
Zdroj: Microbiology (New York), 155, Pt 12, pp. 4135-44
Microbiology (New York), 155, 4135-44
Microbiology (Reading, England), 155(Pt 12), 4135-4144. Microbiology Society
ISSN: 1465-2080
1350-0872
0026-2617
Popis: Otitis media (OM) is one of the most frequent diseases in childhood, andStreptococcus pneumoniaeis among the main causative bacterial agents. Since current experimental models used to study the bacterial pathogenesis of OM have several limitations, such as the invasiveness of the experimental procedures, we developed a non-invasive murine OM model. In our model, adapted from a previously developed rat OM model, a pressure cabin is used in which a 40 kPa pressure increase is applied to translocate pneumococci from the nasopharyngeal cavity into both mouse middle ears. Wild-type pneumococci were found to persist in the middle ear cavity for 144 h after infection, with a maximum bacterial load at 96 h. Inflammation was confirmed at 96 and 144 h post-infection by IL-1βand TNF-αcytokine analysis and histopathology. Subsequently, we investigated the contribution of two surface-associated pneumococcal proteins, the streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A (PpmA), to experimental OM in our model. Pneumococci lacking theslrAgene, but not those lacking theppmAgene, were significantly reduced in virulence in the OM model. Importantly, pneumococci lacking both genes were significantly more attenuated than the ΔslrAsingle mutant. This additive effect suggests that SlrA and PpmA exert complementary functions during experimental OM. In conclusion, we have developed a highly reproducible and non-invasive murine infection model for pneumococcal OM using a pressure cabin, which is very suitable to study pneumococcal pathogenesis and virulencein vivo.
Databáze: OpenAIRE
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