An Escherichia coli Nissle 1917 missense mutant colonizes the streptomycin-treated mouse intestine better than the wild type but is not a better probiotic.
Previously we reported that the streptomycin-treated mouse intestine selected for two different Escherichia coli MG1655 mutants with improved colonizing ability: nonmotile E. coli MG1655 flhDC deletion mutants that grew 15% faster in vitro in mouse cecal mucus and motile E. coli MG1655 envZ missense mutants that grew slower in vitro in mouse cecal mucus yet were able to cocolonize with the faster-growing flhDC mutants. The E. coli MG1655 envZ gene encodes a histidine kinase that is a member of the envZ-ompR two-component signal transduction system, which regulates outer membrane protein profiles. In the present investigation, the envZP41L gene was transferred from the intestinally selected E. coli MG1655 mutant to E. coli Nissle 1917, a human probiotic strain used to treat gastrointestinal infections. Both the E. coli MG1655 and E. coli Nissle 1917 strains containing envZP41L produced more phosphorylated OmpR than their parents. The E. coli Nissle 1917 strain containing envZP41L also became more resistant to bile salts and colicin V and grew 50% slower in vitro in mucus and 15% to 30% slower on several sugars present in mucus, yet it was a 10-fold better colonizer than E. coli Nissle 1917. However, E. coli Nissle 1917 envZP41L was not better at preventing colonization by enterohemorrhagic E. coli EDL933. The data can be explained according to our "restaurant" hypothesis for commensal E. coli strains, i.e., that they colonize the intestine as sessile members of mixed biofilms, obtaining the sugars they need for growth locally, but compete for sugars with invading E. coli pathogens planktonically.
Department of Cell and Molecular Biology, University of Rhode Island, Kingston, Rhode Island, USA.
Jimmy
J
Adediran
Mary P
MP
Leatham-Jensen
Matthew E
ME
Mokszycki
Jakob
J
Frimodt-Møller
Karen A
KA
Krogfelt
Krystyna
K
Kazmierczak
Linda J
LJ
Kenney
Tyrrell
T
Conway
Paul S
PS
Cohen
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense; D019936:Probiotics; D015534:Trans-Activators / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D015534:Trans-Activators; C112177:osmolarity response regulator proteins; C057843:envZ protein, E coli