Microbiology

Circumventing Host Mismatches

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Science  15 Jun 2007:
Vol. 316, Issue 5831, pp. 1542-1543
DOI: 10.1126/science.316.5831.1542d

For many human pathogens, the molecular features of host specificity have not been defined, and this presents a hindrance to developing faithful animal models for diseases. A notable exception is the foodborne bacterium Listeria monocytogenes, in which the virulence factors internalin A and B and their host targets (E-cadherin and hepatocyte growth factor receptor, respectively) are known to promote adherence (the first step in infection) to nonphagocytic host cells. One successful way of making a laboratory model for listeriosis has been to humanize mouse gut epithelium by introducing human E-cadherin, but this can add unexpected variables to experimentation. Wollert et al. have taken the obverse approach and adapted the pathogen to the mouse by using structure-based design to make individual amino acid substitutions in internalin A. Substitution of the proline at position 16 by glutamate together with a second substitution of a glutamate by a glutamine appears to equalize the binding affinities of internalin A for human and mouse E-cadherins. In vivo experiments confirmed that the engineered bacteria were competent to colonize the villi of mouse guts and cause systemic listeriosis. — CA

Cell 129, 891 (2007).

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