Open AccessVitamin A supplementation boosts control of antibiotic-resistant Salmonella infection in malnourished mice
Author(s) -
Annica R. Stull-Lane,
Kristen L. Lokken-Toyli,
Vladimir E. Diaz-Ochoa,
G. Walker,
Stephanie A. Cevallos,
Andromeda L.N. Winter,
Ariel Del Hoyo Muñoz,
Guo Xiang Yang,
Eric M. Velazquez,
Chun Yi Wu,
Renée M. Tsolis
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008737
Subject(s) - context (archaeology) , bacteremia , antibiotics , malnutrition , medicine , salmonella enterica , vitamin , antibiotic resistance , vitamin d deficiency , micronutrient , immunology , vitamin d and neurology , salmonella , biology , microbiology and biotechnology , pathology , bacteria , paleontology , genetics
Disseminated disease from non-typhoidal Salmonella enterica strains results in >20% mortality globally. Barriers to effective treatment include emerging multidrug resistance, antibiotic treatment failure, and risk factors such as malnutrition and related micronutrient deficiencies. Individuals in sub-Saharan Africa are disproportionately affected by non-typhoidal S . enterica bloodstream infections. To inform a clinical trial in people, we investigated vitamin A as a treatment in the context of antibiotic treatment failure in a mouse model of vitamin A deficiency. Vitamin A-deficient (VAD) mice exhibited higher systemic bacterial levels with a multidrug-resistant clinical isolate in comparison to mice on a control diet. Sex-specific differences in vitamin A deficiency and disseminated infection with S . enterica serotype Typhimurium ( S . Typhimurium) were observed. VAD male mice had decreased weight gain compared to control male mice. Further, infected VAD male mice had significant weight loss and decreased survival during the course of infection. These differences were not apparent in female mice. In a model of disseminated S . Typhimurium infection and antibiotic treatment failure, we assessed the potential of two consecutive doses of vitamin A in alleviating infection in male and female mice on a VAD or control diet. We found that subtherapeutic antibiotic treatment synergized with vitamin A treatment in infected VAD male mice, significantly decreasing systemic bacterial levels, mitigating weight loss and improving survival. These results suggest that assessing vitamin A as a therapy during bacteremia in malnourished patients may lead to improved health outcomes in a subset of patients, especially in the context of antibiotic treatment failure.