2026-10-11T22:37:13Z
https://api.figshare.com/v2/oai
oai:figshare.com:article/33968342
2026-09-22T17:42:03Z
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<p>RT-qPCR primer sequences used in this study.</p>
Mengping He (10286601)
Jinju Cai (25091351)
Huihui Wu (531100)
Tianqi Xu (9574329)
Haijie Zhang (754292)
Zhiqiang Wang (48987)
Yuan Liu (88411)
Biochemistry
Space Science
Microbiology
Cell Biology
Physiology
Environmental Sciences not elsewhere classified
Science Policy
Immunology
Biological Sciences not elsewhere classified
Infectious Diseases
κb signaling pathway
typhoidal salmonellosis globally
reduces bacterial loads
polarized inflammatory responses
maintaining membrane stability
facilitating bacterial division
deletion disrupts peptidoglycan
eliminate intracellular bacteria
findings establish nlpd
intracellular survival
vivo </
vitro </
targeting compound
salmonella </
nlpd </
murine models
mediated nf
mechanisms governing
lysosomal activation
lipopolysaccharide homeostasis
limits m1
like receptor
leading cause
insertion sequencing
critical regulator
critical gene
>- deficient
<div><p><i>Salmonella</i> 4,[5],12:i:- has emerged as a leading cause of non-typhoidal salmonellosis globally, yet the mechanisms governing its intracellular survival and pathogenic adaptation remain unclear. Herein, through transposon-insertion sequencing, we identify <i>nlpD</i>, a peptidoglycan hydrolase activator essential for maintaining membrane stability and facilitating bacterial division, as a critical gene for <i>Salmonella</i> infection. <i>nlpD</i>-deficient <i>Salmonella</i> exhibits significantly diminished survival in both <i>in vitro</i> and <i>in vivo</i> settings. Mechanistically, <i>nlpD</i> deletion disrupts peptidoglycan and lipopolysaccharide homeostasis, rendering <i>Salmonella</i> more vulnerable to oxidative and acidic stresses within phagosomes. Accumulated cell wall components robustly activate the toll-like receptor-mediated NF-κB signaling pathway, driving M1 macrophage polarization and autophagy-lysosomal activation to eliminate intracellular bacteria. An FDA-approved drug screen identifies ketoconazole as an NlpD-targeting compound that reduces bacterial loads in murine models. Our findings establish NlpD as a critical regulator that limits M1-polarized inflammatory responses, highlighting its potential as a therapeutic vulnerability against <i>Salmonella</i> 4,[5],12:i:- infection.</p></div>
2026-09-22T18:00:21Z
Dataset
Dataset
10.1371/journal.ppat.1014640.s017
https://figshare.com/articles/dataset/_p_RT-qPCR_primer_sequences_used_in_this_study_p_/33968342
CC BY 4.0