Streptococcuspyogenes infects human endometrium by limiting the innate immune response

Weckel, Antonin; Guilbert, Thomas; Lambert, Clara; Plainvert, Céline; Goffinet, François; Poyart, Claire; Méhats, Céline; Fouet, Agnès

doi:10.1172/jci130746

Cited by 6 publications

(10 citation statements)

References 66 publications

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“…mFabT strain capacity to colonize human tissue ex vivo was assessed by measuring its growth on human tissue. As emm28 strains are associated to puerperal fever 20,21 , we compared ex vivo growth of WT and mFabT on human decidua 22 . In control experiments, both strains failed to grow in RPMI, as assessed by growth ratios between cfus after 8 h incubation and the inocula (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This led to the deletion of fabT from nucleotides 49 to 389, as confirmed by PCR. The mFabT eryR -i gfp strain harboring an integrated inducible gfp gene was constructed as described for the WT eryR -i gfp strain 22 . Whole genome sequencing was performed on the mFabT and mFabT eryR -i gfp constructed strains, and no surreptitious mutations were found (Bioproject PRJNA926803, accession number SAMN34247893 for mFabT, SAMN34247911 for mFabT eryR -i gfp ).…”

Section: Methodsmentioning

confidence: 99%

“…Human placentas with attached maternal-fetal membranes were collected and processed as described 22 with the following modifications. Tissues were obtained after vaginal delivery, and the samples used were from regions located far from the cervix, known as zone of intact morphology 41 .…”

Section: Ex Vivo Gas Growth Capacity Analysismentioning

confidence: 99%

“…Ex vivo assessment of GAS WT and mFabT growth on muscle (meat) lipids WT eryR-igfp and mFabT eryR-igfp strains (Supplementary Table 7) 22 were grown overnight in BHI (Ery 5), and then diluted to OD600 = 0.05 in FA-free bovine serum albumin (referred to as BSA; 0.025%) plus C17:1 100 µM in 1 ml, without or with platensimycin 1 µg/ml, with Ery 5 for selection. After 4 h growth, culture densities were adjusted to OD600 = 1 in BHI, and 35 µl were spread on 5 cm diameter plates containing 5 ml BHI agar plus BSA 0.025% and C17:1 100 µM, without or with platensimycin 0.5 µg/ml, with Ery 5 for selection.…”

Section: Spontaneous Fabt Mutant Isolationmentioning

confidence: 99%

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The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

Lambert,

Gaillard,

Wongdontree

et al. 2023

Preprint

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In Streptococcus pyogenes, the fatty acid (FA) synthesis pathway FASII is feedback-controlled by the FabT repressor bound to an acyl-Acyl carrier protein. FabT defects are associated with attenuated virulence in animal models. Nevertheless, fabT point mutations arise in vivo. To resolve this paradox, we identified conditions and biotopes in which fabT behavior is defective, as being human tissues, cells, or cell filtrates. We then defined biotopes in which fabT mutants have a growth advantage, as being lipid rich. In a proof of concept we demonstrate that fabT mutants emerge in this context, due to FASII derepression, which prevents environmental FA incorporation. Energy dissipation is identified as the principal defect of fabT mutants, such that specific nutrients are consumed but do not promote growth. Our findings elucidate the nature of the link between FabT and virulence, provide a rationale for fabT mutant emergence, and identify the defect that causes attenuated fabT infection.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ex Vivo Gas Growth Capacity Analysismentioning

confidence: 99%

Section: Spontaneous Fabt Mutant Isolationmentioning

confidence: 99%

See 2 more Smart Citations

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

Lambert,

Gaillard,

Wongdontree

et al. 2023

Preprint

Self Cite

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“…The immune system has been traditionally classified into two categories: the adaptive immune system and the innate immune system [ 23 ]. Innate immunity consists of a series of physical, chemical, and anatomical barriers [ 24 ] that act as the first line of defense against all types of infectious agents, including extra [ 25 ] and intracellular [ 26 ] bacteria, viruses [ 27 ], fungi [ 28 ], protozoa [ 29 ], and helminths [ 30 ].…”

Section: Innate Immunitymentioning

confidence: 99%

The Multiple Faces of Nitric Oxide in Chronic Granulomatous Disease: A Comprehensive Update

et al. 2022

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Nitric oxide (NO), a signaling molecule, regulates multiple biological functions, including a variety of physiological and pathological processes. In this regard, NO participates in cutaneous inflammations, modulation of mitochondrial functions, vascular diseases, COVID-19, neurologic diseases, and obesity. It also mediates changes in the skeletal muscle function. Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by the malfunction of phagocytes caused by mutations in some of the genes encoding subunits of the superoxide-generating phagocyte NADPH (NOX). The literature consulted shows that there is a relationship between the production of NO and the NADPH oxidase system, which regulates the persistence of NO in the medium. Nevertheless, the underlying mechanisms of the effects of NO on CGD remain unknown. In this paper, we briefly review the regulatory role of NO in CGD and its potential underlying mechanisms.

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A new perspective in pyroptosis: lifting the veil on GSDMA activation

Chen

Peng

2023

Front. Med.

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Streptococcuspyogenes infects human endometrium by limiting the innate immune response

Cited by 6 publications

References 66 publications

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

The Multiple Faces of Nitric Oxide in Chronic Granulomatous Disease: A Comprehensive Update

A new perspective in pyroptosis: lifting the veil on GSDMA activation

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