Shigella flexneri remodeling and consumption of host lipids during infection
Date
2023
Authors
Ascari, A.
Frölich, S.
Zang, M.
Tran, E.N.H.
Wilson, D.W.
Morona, R.
Eijkelkamp, B.A.
Editors
Galperin, M.Y.
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Journal article
Citation
Journal of Bacteriology, 2023; 205(12):1-18
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Alice Ascari, Sonja Frölich, Maoge Zang, Elizabeth N. H. Tran, Danny W. Wilson, Renato Morona, Bart A. Eijkelkamp
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Abstract
Shigella flexneri is a major cause of bacillary dysentery in the developing world, predominantly affecting the pediatric age group, with malnutrition being a common co-morbidity. Lipids are key nutritional components, and their abundance and composition are likely to influence the pathobiology of S. flexneri. S. flexneri expresses a plethora of polysaccharides on its cell surface, but how this hydrophilic surface layer influences S. flexneri interaction with hydrophobic host molecules, such as fatty acids and lipids, is not well understood. In this study, we sought to interrogate how this hydrophilic layer affects S. flexneri during its intracellular lifestyle and how lipid homeostasis changes in both the host and pathogen. We characterized changes in S. flexneri cell envelope composition and surface-associated glycolipids, in particular lipopolysaccharide (LPS), during different phases of infection. We found that a dynamic capacity in LPS expression is necessary for the pathogen to manage delicate interaction with host fatty acids and maintain optimum virulence. Additionally, through confocal immunofluorescent microscopy, coupled with transcriptional and lipid analyses, we demonstrate that S. flexneri induces major host lipid remodeling during infection, by hijacking host lipid homeostasis pathways to its own benefit. Finally, this study suggests that fatty acid supplementation can influence the persistence and magnitude of S. flexneri infection. This work provides novel insights into the potential roles of balanced and sufficient dietary fatty acid intake in protection against gastroenteric pathogen infection.
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© 2023 American Society for Microbiology. All Rights Reserved.