Genome-wide analysis exploring mechanisms used by Shigella sonnei to survive long-term nutrient starvation
Author(s)
Type
Journal Article
Abstract
Shigella is a major cause of severe diarrhea, with Shigella flexneri and Shigella sonnei accounting for over 90% of infections. Progressive economic growth worldwide correlates with the replacement of S. flexneri by S. sonnei as the dominant cause of shigellosis. The basis of the epidemiological shift remains unclear, but it highlights the urgent need for further studies on the increasingly prevalent, but less well-studied, S. sonnei. Here, we investigated whether S. sonnei is better equipped to survive nutrient starvation, a crucial condition for persistence both outside the host and within the colonic lumen. S. sonnei exhibited greater survival under long-term nutrient starvation (LTNS) than S. flexneri, rapidly activating survival mechanisms. We interrogated the genome of S. sonnei using transposon-directed insertion-site sequencing (TraDIS), revealing that metabolic pathways (ATP, nucleotide, and amino acid synthesis) and envelope homeostasis systems (e.g., Tol-Pal complex, Bam complex, peptidoglycan recycling, and RpoE stress response) are conditionally essential for LTNS. TraDIS findings were validated by non-competitive and competitive survival of wild-type and deletion mutant strains. We compared the homology of conditionally essential genes between S. sonnei and S. flexneri to identify genes potentially involved in differential LTNS survival between the species. However, S. sonnei strains in which a single gene was replaced with the S. flexneri allele showed wild-type survival phenotypes. This suggests that the divergent survival of these two species may be more complex than a monogenic difference. Together, these data define the molecular adaptations of starvation resistance in S. sonnei and provide insights into its epidemiological dominance in high-income countries.
worldwide correlates with the replacement of S. flexneri by S. sonnei as the dominant cause of shigellosis. The basis of the epidemiological shift remains unclear, but it
highlights the urgent need for further studies on the increasingly prevalent, but less well-studied, S. sonnei. Here, we investigated whether S. sonnei is better equipped to survive nutrient starvation, a crucial condition for persistence both outside the host and
within the colonic lumen. S. sonnei exhibited greater survival under long-term nutrient starvation (LTNS) than S. flexneri, rapidly activating survival mechanisms. We interrogated the genome of S. sonnei using transposon-directed insertion-site sequencing (TraDIS), revealing that metabolic pathways (ATP, nucleotide, and amino acid synthesis) and envelope homeostasis systems (e.g., Tol-Pal complex, Bam complex, peptidoglycan recycling, and RpoE stress response) are conditionally essential for LTNS. TraDIS findings were validated by non-competitive and competitive survival of wild-type and deletion
mutant strains. We compared the homology of conditionally essential genes between S. sonnei and S. flexneri to identify genes potentially involved in differential LTNS survival between the species. However, S. sonnei strains in which a single gene was replaced
with the S. !exneri allele showed wild-type survival phenotypes. This suggests that the divergent survival of these two species may be more complex than a monogenic difference. Together, these data define the molecular adaptations of starvation resistance
in S. sonnei and provide insights into its epidemiological dominance in high-income countries.
worldwide correlates with the replacement of S. flexneri by S. sonnei as the dominant cause of shigellosis. The basis of the epidemiological shift remains unclear, but it
highlights the urgent need for further studies on the increasingly prevalent, but less well-studied, S. sonnei. Here, we investigated whether S. sonnei is better equipped to survive nutrient starvation, a crucial condition for persistence both outside the host and
within the colonic lumen. S. sonnei exhibited greater survival under long-term nutrient starvation (LTNS) than S. flexneri, rapidly activating survival mechanisms. We interrogated the genome of S. sonnei using transposon-directed insertion-site sequencing (TraDIS), revealing that metabolic pathways (ATP, nucleotide, and amino acid synthesis) and envelope homeostasis systems (e.g., Tol-Pal complex, Bam complex, peptidoglycan recycling, and RpoE stress response) are conditionally essential for LTNS. TraDIS findings were validated by non-competitive and competitive survival of wild-type and deletion
mutant strains. We compared the homology of conditionally essential genes between S. sonnei and S. flexneri to identify genes potentially involved in differential LTNS survival between the species. However, S. sonnei strains in which a single gene was replaced
with the S. !exneri allele showed wild-type survival phenotypes. This suggests that the divergent survival of these two species may be more complex than a monogenic difference. Together, these data define the molecular adaptations of starvation resistance
in S. sonnei and provide insights into its epidemiological dominance in high-income countries.
Date Issued
2026-04-21
Date Acceptance
2026-02-11
Citation
mSystems, 2026, 11 (4)
ISSN
2379-5077
Publisher
American Society for Microbiology
Journal / Book Title
mSystems
Volume
11
Issue
4
Copyright Statement
Copyright © 2026 Matanza et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Identifier
10.1128/msystems.00088-26
Subjects
Shigella
nutrient starvation
Tn-seq
microbial metabolism
bacterial cell envelope by 2a02:c7c:3708:7300:46e5:17ff:fea5:4ec
Publication Status
Published
Article Number
e00088-26
Date Publish Online
2026-03-16