title: β-Carotene Biosynthesis in Probiotic Bacteria.
abstract: Susceptibility to deadly diarrheal diseases is partly due to widespread pediatric vitamin A deficiency. To increase vitamin A coverage in malnourished children, we propose to engineer a probiotic bacterium that will produce β-carotene in the intestine, which will be metabolized to vitamin A. Such a therapy has the potential to broadly stimulate mucosal immunity and simultaneously reduce the incidence and duration of diarrheal disease. To that end, a β-carotene-producing variant of the probiotic Escherichia coli strain Nissle 1917 (EcN-BETA) was generated. Notably, the strain produces β-carotene under anaerobic conditions, reflective of the gut environment. EcN-BETA also retains β-carotene production capability after lyophilization, suggesting that it may be amenable to dry formulation. Moreover, EcN-BETA activates murine dendritic cells in vitro, suggesting that the presence of β-carotene may not diminish the immunostimulatory capacity of EcN. Finally, we present a framework through which further improvements may enable approaches such as the one described in this report to yield innovative life-saving therapies for the developing world.
authors.affiliation: Biosciences Division, SRI International, Harrisonburg, VA, 22802, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Miller
authors.affiliation: Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
authors.forename: M Travis
authors.initials: MT
authors.lastname: Harrison
authors.affiliation: Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Andrea
authors.affiliation: Biosciences Division, SRI International, Harrisonburg, VA, 22802, USA.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Endsley
authors.affiliation: Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yin
authors.affiliation: Biosciences Division, SRI International, Harrisonburg, VA, 22802, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kodukula
authors.affiliation: Biosciences Division, SRI International, Harrisonburg, VA, 22802, USA. watson.douglas@gmail.com.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Watson
keywords: Diarrheal disease; Mucosal immunity; Pediatric malnutrition; Probiotic; Vitamin A deficiency; β-Carotene