Vitamin A supplementation boosts control of antibiotic-resistant Salmonella infection in malnourished mice

• Published in: PLoS neglected tropical diseases Vol. 14; no. 10; p. e0008737
• Main Authors: Stull-Lane, Annica R, Lokken-Toyli, Kristen L, Diaz-Ochoa, Vladimir E, Walker, Gregory T, Cevallos, Stephanie A, Winter, Andromeda L N, Muñoz, Ariel Del Hoyo, Yang, Guiyan G, Velazquez, Eric M, Wu, Chun-Yi, Tsolis, Renée M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-10-2020; Public Library of Science (PLoS)
• Subjects: Animal protection; Animal welfare; Animals; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; Bacteremia; Bacteremia - drug therapy; Bacteremia - microbiology; Biology and Life Sciences; Body weight gain; Body weight loss; Care and treatment; Context; Control; Diet; Dietary Supplements; Disease Models, Animal; Disseminated infection; Drug resistance; Drug Resistance, Multiple, Bacterial; Experiments; Failure; Female; Females; Health services; Immunology; Infections; Laboratory animals; Liver; Male; Males; Malnutrition; Malnutrition - physiopathology; Medical research; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Microbiological strains; Mortality; Multidrug resistance; Nutrient deficiency; Patients; Physical sciences; Research and Analysis Methods; Retinene; Risk analysis; Risk factors; Salmonella; Salmonella Infections - drug therapy; Salmonella Infections - microbiology; Salmonella typhimurium - drug effects; Salmonellosis; Sex Factors; Strains; Survival; Survival Rate; Therapy; Tropical diseases; Veterinary medicine; Vitamin A; Vitamin A - administration & dosage; Vitamin A deficiency; Vitamin A Deficiency - physiopathology; Vitamins; Weight gain; Weight loss; Sub-Saharan Africa; New York; California; United States > US; China
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0008737

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.