MICROORGANISMS HAVING ATTENUATED INVASIVENESS.

摘要

PCT No. PCT/US93/02265 Sec. 371 Date Sep. 1, 1994 Sec. 102(e) Date Sep. 1, 1994 PCT Filed Mar. 1, 1993 PCT Pub. No. WO93/18165 PCT Pub. Date Sep. 16, 1993The invention provides nucleic acids encoding one or more hyper-invasive genes within the hil locus (hyper-invasion locus) or fragments thereof, methods for making attenuated microorganisms and identifying such hyper-invasive nucleic acids as well as mutant microorganisms wherein one or more hyper-invasive genes within the hil locus are modified to attenuate the invasive phenotype of the microorganism. The methods of the invention utilize conditions which repress invasiveness in an otherwise invasive microorganism. The method comprises mutating an invasive microorganism to form a plurality of mutant microorganisms. The thus formed mutants are exposed to conditions which repress invasiveness of the parental invasive microorganism. At least one mutant microorganism is then detected which exhibits an increase in invasiveness as compared to the parental invasive microorganism. The site of mutation in the genome of the mutant microorganism is then determined to localize and identify one or more hyper-invasive genes within the hil locus of the invasive microorganism.