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

Abstract：

: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.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Stull-Lane AR,Lokken-Toyli KL,Diaz-Ochoa VE,Walker GT,Cevallos SA,Winter ALN,Muñoz ADH,Yang GG,Velazquez EM,Wu CY,Tsolis RM

doi

10.1371/journal.pntd.0008737

subject

Has Abstract

pub_date

2020-10-02 00:00:00

pages

e0008737

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-20-00583

journal_volume

pub_type

杂志文章

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