Development of a novel ex vivo insect model for studying virulence determinants of Escherichia coli K1.
A key step in Escherichia coli K1 meningitis is the crossing of the blood-brain barrier by the bacteria in order to gain entry into the central nervous system (CNS). In this study, a novel ex vivo model to study E. coli K1 invasion of the CNS is described that uses the African migratory locust, Locusta migratoria. By injecting bacteria into isolated locust head capsules, it was demonstrated that E. coli K1 invade the locust brain within 2 h in numbers depending on the concentration of bacteria injected. Using several mutants derived from K1, it was shown that outer-membrane protein A is a critical bacterial determinant required for the E. coli K1 invasion. The isogenic gene-deletion mutants, DeltafimH, Deltacnf1, DeltaneuDB and a rough LPS mutant showed significantly reduced invasion of locust brain. This novel model for the study of E. coli K1 pathogenesis offers several advantages over existing mammalian models in relation to its relative ease of use, cost-effectiveness and ethical acceptability.
Department of Biology, School of Biological and Chemical Sciences, Birkbeck College, University of London, London WC1E 7HX, UK.
Behzad
B
Mokri-Moayyed
Department of Biology, School of Biological and Chemical Sciences, Birkbeck College, University of London, London WC1E 7HX, UK.
Graham John
GJ
Goldsworthy
Department of Biology, School of Biological and Chemical Sciences, Birkbeck College, University of London, London WC1E 7HX, UK.
Naveed Ahmed
NA
Khan
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics; D002490:Central Nervous System; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D048188:Locusta migratoria / Q000382:microbiology*; D008954:Models, Biological; D014774:Virulence / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology
D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D037521:Virulence Factors; C078167:OMPA outer membrane proteins