Biology subjects

Masse, E.

Publications and source records attributed to Masse, E..

9 recordsLinked to original sources

bioRxiv2026

Regulation of PL fimbriae (plf) and role of PlfB as a negative regulator during avian pathogenic Escherichia coli infection in turkeys

Little is currently known about the regulation of PL fimbriae produced by some pathogenic E. coli strains. We identified PlfB, a transcriptional regulator of the PapB family, as a negative regulator of PL fimbriae (Plf). Deletion of plfB significantly increased plfA transcription and Plf production. PlfB bound specifically to the plfA promoter region. Using a PplfA-lux reporter system, the deletion of plfB caused sustained and increased expression across serial passages. Global regulatory genes such as lrp, argR, and hns were also implicated in regulation of plf expression. Loss of lrp or argR decreased plf expression, suggesting these regulators positively regulate PL fimbriae. By contrast, loss of hns increased levels of plf expression, supporting its role as a negative regulator. Interestingly, loss of plfB significantly increased bacterial colonization in the lung of 6-day-old turkey poults. Further, complementation of plfB restored plf fimbrial expression and colonization of turkey lungs to wild-type levels. This further supports an important role for PL fimbriae for colonization of turkey lungs, since loss of plfB which resulted in increased plf gene expression in turkey lungs also correlated with higher bacterial numbers in the lungs. Taken together, these results indicate that PlfB acts as a negative regulator to reduce levels of PL fimbrial expression, under some conditions, but that it is not required for plf expression. This contrasts with the role the PapB regulator, which has been shown to play an essential role in expression of P fimbriae in uropathogenic E. coli strains.

microbiology↗

bioRxiv2026

Peptidoglycan remodeling prevents antibiotic resistance during oxidative stress

ABSTRACT: The bacterial small RNA (sRNA) OxyS is expressed in Escherichia coli during oxidative stress. The sRNA OxyS enhances cell survival by controlling genes involved in the regulation of hydrogen peroxide (H2O2) and iron-sulfur (Fe-S) cluster formation. Here, we used the MS2 affinity purification coupled with RNA sequencing (MAPS) technique to identify new target mRNAs of the sRNA OxyS. Our analysis revealed a significant enrichment of mepS mRNA, which encodes a peptidoglycan endopeptidase that promotes cell growth. Our results confirm a previous report on the sRNA OxyS repressing the translation of mepS. We also found that an {Delta}oxyS background facilitates the emergence of mutations, conferring increased resistance to the last-resort antibiotics polymyxin B and E (colistin), but only in the presence of the target mepS gene. This suggests that the translation repression of mepS by OxyS could prevent mutations in bacterial DNA during H2O2-induced oxidative stress. Moreover, we show that adding the antioxidant thiourea or sequestering iron in the {Delta}oxyS background effectively reduces the emergence of resistance against both polymyxin B and colistin. These results suggest that reactive oxygen species (ROS), in conjunction with intracellular iron, play a key role in driving the emergence of antibiotic resistance. Overall, our work underlines a mechanism of antimicrobial emergence implicating oxidative stress, intracellular Fe, and cell wall remodeling in E. coli. IMPORTANCE: This study uncovers an underexplored link between peptidoglycan remodeling and oxidative stress responses during exposure to antibiotics. By elucidating how MepS and the sRNA OxyS interact in the presence of polymyxins and oxidative stress, our study suggests that MepS may exert an anti-mutator function. The repression of mepS translation by OxyS seems to limit the emergence of antibiotic resistance driven by DNA mutations. Together, these findings suggest cell wall remodeling and oxidative stress response pathways as promising targets to enhance antibiotic efficacy and limit the emergence of resistance.

microbiology↗

bioRxiv2026

SOCS1 expression in prostate epithelial cells is essential for tissue homeostasis and tumor suppression

Suppressor of cytokine signaling 1 (SOCS1) negative regulates inflammatory cytokine production and attenuates oncogenic growth factor signaling pathways. Reduced SOCS1 protein expression in human prostate cancer correlates with greater disease severity. To define the physiological functions of SOCS1 functions in the prostate, we conditionally ablated Socs1 in prostate epithelial cells of C57BL/6 mice. These Socs1{Delta}PE mice exhibited normal prostate development, maturation and lobular architecture. However, adult Socs1{Delta}PEmice developed progressive epithelial hyperplasia and inflammatory cell infiltration that were temporally and spatially distinct. SOCS1-deficient prostate showed increased epithelial cell proliferation and elevated oxidative stress markers, and prostate organoids recapitulated this hyperplasia phenotype. Diet-induced obesity exacerbated both hyperplasia and inflammation in SOCS1-deficient prostate. Upon transurethral infection with uropathogenic Escherichia coli UPEC1677 expressing the genotoxin colibactin, Socs1{Delta}PE mice developed invasive prostate cancer with complete loss of lobular architecture, whereas control mice developed hyperplasia and pre-neoplastic lesions. In vitro, SOCS1-deficient prostate organoid-derived epithelial cells exhibited increased DNA damage following exposure to UPEC1677. Deletion of the colibactin biosynthetic gene clbP in UPEC1677 abolished its ability to induce DNA damage in SOCS1-deficient cells and to drive prostate cancer in vivo. Proteomic analysis of prostate organoids revealed dysregulation of basal and luminal epithelial lineage markers and signaling pathway proteins that could promote neoplasia in SOCS1-deficient cells. Collectively, these findings establish an essential, epithelial cell-intrinsic role for SOCS1 in maintaining prostate tissue homeostasis by restraining proliferation, regulating lineage plasticity, limiting inflammation and oxidative stress, and conferring protection against genotoxic injury and neoplastic transformation.

cancer biology↗

bioRxiv2025

Ketogenic interventions prevent alterations of the gut microbiome in transgenic Alzheimer Disease mice

Alterations in the gut microbiome constitute a feature of aging and therefore represent a therapeutic target for aging-related diseases. In this study, we investigated the impact of ketogenic interventions on the microbiome of mice genetically predisposed to Alzheimers disease (AD). AD mice exhibited several microbial alterations, notably increased levels of Bifidobacterium and decreased levels of Bacteroidetes. Ketogenic interventions, either a medium-chain triglyceride-enriched diet (MCT) or carbohydrate-free high-fat diet (CFHF), administered for 1 month restored the levels of more than 50% of the bacteria altered in AD mice, including a strong reduction in Bifidobacterium levels. Ketogenic interventions induced a shift in the gut microbiome associated with increased levels of short-chain fatty acid-producing bacteria, such as Lachnospiraceae and Muribaculaceae. MCT and CFHF also triggered diet-specific microbial changes, which may contribute to the distinct physiological effects of these diets. In conclusion, ketogenic interventions may influence AD pathophysiology by modulating the gut microbiome.

neuroscience↗

bioRxiv2024

An unprecedented small RNA-riboswitch interaction controls expression of a bifunctional pump that is essential for Staphylococcus aureus infection

Maintaining manganese and iron homeostasis is critical for the human pathogen Staphylococcus aureus. To counteract metal-based host defense strategies (e.g., nutritional immunity, metal poisoning), S. aureus uses a combination of metal-sensing transcription factors and regulatory RNAs to maintain metal homeostasis. In this study, we uncovered an unprecedented interaction between a cis- and a trans-acting regulatory RNA controlling a conditionally essential gene, mntY, encoding a Mn efflux pump. This broadly conserved RNA-RNA interaction between a Fe-responsive sRNA and a Mn-sensing riboswitch allows the integration of Feand Mn-related stresses, notably encountered at the infection site, to fine-tune mntY expression. Remarkably, deletion of the mntY gene is strongly pleomorphic, causing growth defects, altering virulence factor expression, immune evasion, and survival during infection. We demonstrated that MntY is critical for the adaptation of S. aureus to both low and high Mn environments, due to its dual role in metalation of Mn-dependent exoenzymes and Mn detoxification. These findings point to MntY as a promising new therapeutic target to combat multidrug-resistant staphylococcal infections.

microbiology↗

bioRxiv2023

Mechanisms of regulation of cryptic prophage-encoded gene products in Escherichia coli

The dicBF operon of Qin cryptic prophage in Escherichia coli K12 encodes the small RNA (sRNA) DicF and small protein DicB, which regulate host cell division and are toxic when overexpressed. While new functions of DicB and DicF have been identified in recent years, the mechanisms controlling the expression of the dicBF operon have remained unclear. Under standard laboratory growth conditions, transcription from dicBp, the major promoter of the dicBF operon, is repressed by DicA. Here, we discovered that transcription of the dicBF operon and processing of the polycistronic mRNA is regulated by multiple mechanisms. DicF sRNA accumulates during stationary phase and is processed from the polycistronic dicBF mRNA by the action of both RNase III and RNase E. DicA-mediated transcriptional repression of dicBp can be relieved by an antirepressor protein, Rem, encoded on the Qin prophage. Ectopic production of Rem results in cell filamentation due to strong induction of the dicBF operon and filamentation is mediated by DicF and DicB. Spontaneous derepression of dicBp occurs in a subpopulation of cells independent of the antirepressor. This phenomenon is reminiscent of the bistable switch of {lambda} phage with DicA and DicC performing functions similar to CI and Cro, respectively. Additional experiments demonstrate stress-dependent induction of the dicBF operon. Collectively, our results illustrate that toxic genes encoded on cryptic prophages are subject to layered mechanisms of control, some that are derived from the ancestral phage and some that are likely later adaptations. ImportanceCryptic or defective prophages have lost genes necessary to excise from the bacterial chromosome and produce phage progeny. In recent years, studies have found that cryptic prophage gene products influence diverse aspects of bacterial host cell physiology. However, to obtain a complete understanding of the relationship between cryptic prophages and the host bacterium, identification of the environmental, host or prophage-encoded factors that induce the expression of cryptic prophage genes is crucial. In this study, we examine the regulation of a cryptic prophage operon in Escherichia coli encoding a small RNA and a small protein that are involved in inhibiting bacterial cell division, altering host metabolism, and protecting the host bacterium from phage infections.

microbiology↗

bioRxiv2021

Escherichia coli ribosomal protein S1 enhances the kinetics of ribosome biogenesis and RNA decay

Escherichia coli ribosomal protein S1 is essential for translation initiation of mRNAs and for cellular viability. Two oligonucleotide binding (OB)-fold domains located in the C-terminus of S1 are dispensable for growth, but their deletion causes a cold-shock phenotype, loss of motility and deregulation of RNA mediated stress responses. Surprisingly, the expression of the small regulatory RNA RyhB and one of its repressed target mRNA, sodB, are enhanced in the mutant strain lacking the two OB domains. Using in vivo and in vitro approaches, we show that RyhB retains its capacity to repress translation of target mRNAs in the mutant strain but becomes deficient in triggering rapid turnover of those transcripts. In addition, the mutant is defective in of the final step of the RNase E-dependent maturation of the 16S rRNA. This work unveils an unexpected function of S1 in facilitating ribosome biogenesis and RyhB-dependent mRNA decay mediated by the RNA degradosome. Through its RNA chaperone activity, S1 participates to the coupling between ribosome biogenesis, translation, and RNA decay.

microbiology↗

bioRxiv2020

Dynamic interactions between the RNA chaperone Hfq, small regulatory RNAs and mRNAs in live bacterial cells

RNA binding proteins play myriad roles in controlling and regulating RNAs and RNA-mediated functions, often through simultaneous binding to other cellular factors. In bacteria, the RNA chaperone Hfq modulates post-transcriptional gene regulation. Absence of Hfq leads to the loss of fitness and compromises the virulence of bacterial pathogens. Using live-cell super-resolution imaging, we are able to distinguish Hfq binding to different sizes of cellular RNAs. We demonstrate that under normal growth conditions, Hfq exhibits widespread mRNA binding activity. Particularly, the distal face of Hfq contributes mostly to the mRNA binding in vivo. In addition, binding of Hfq to these mRNAs can recruit RNase E to promote turnover of these mRNAs in an sRNA-independent manner, providing one mechanism to release Hfq from the pre-bound mRNAs. Finally, our data indicate that sRNAs, once expressed, can either co-occupy Hfq with the mRNA or displace the mRNA from Hfq, suggesting mechanisms through which sRNAs rapidly access Hfq to induce sRNA-mediated gene regulation. Our data collectively demonstrate that Hfq dynamically changes its interactions with different RNAs in response to changes in cellular conditions.

biophysics↗

bioRxiv2019

CcnA, a novel non-coding RNA regulating the bacterial cell cycle

Bacteria are powerful models for understanding how cells divide and accomplish global regulatory programs. In Caulobacter crescentus, a cascade of essential master regulators supervises the correct and sequential activation of DNA replication, cell division and development of different cell types. Among them, the response regulator CtrA plays a crucial role coordinating all those functions. Here, for the first time we describe the role of a novel factor named CcnA, a cell cycle regulated ncRNA located at the origin of replication, presumably activated by CtrA and responsible for the accumulation of CtrA itself. In addition, CcnA may be also involved in the inhibition of translation of the S-phase regulator, GcrA, by interacting with its 5 untranslated region (5-UTR). Performing in vitro experiments and mutagenesis, we propose a mechanism of action of CcnA based on liberation (ctrA) or sequestration (gcrA) of their ribosome-binding site (RBS). Finally, its role may be conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a potentially conserved process modulating cell cycle in Caulobacterales and Rhizobiales.

microbiology↗