Flora Llense

Institute for Biology Paris-Seine; Paris, France; IBPS

blind loop syndrome

An intestinal disease characterized by a dysbalance of the bacterial flora of the small intestine, causing derangement to the normal physiological processes of digestion and absorption.

commensal bacterial infectious disease

A bacterial infectious disease that results_in infection by bacteria which are part of the normal human flora when one or more of the defense mechanisms designed to restrict them from the usually sterile internal tissues are breached by accident, by intent (surgery), or by an underlying metabolic or an infectious disorder.

cellulitis

A skin disease where there is a diffuse infection of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken: cracks in the skin, cuts, blisters, burns, insect bites, surgical wounds, or sites of intravenous catheter insertion.

Pasti, Gabriella et al. (2017) International Worm Meeting "Extrinsic stress triggers an actin-based viscoplastic process to drive tissue elongation."

Kim, Samantha, FERRARO, Teresa, Rodriguez, David, PONTABRY, Julien, Labouesse, Michel, Gally, Christelle, Lardennois, Alicia, Pasti, Gabriella, Llense, Flora

[International Worm Meeting, 2017]

Embryonic morphogenesis refers to changes in the shape and position of cells within the embryo. While it is clearly established that mechanical forces induced by molecular motors play a critical role in driving these changes, proper understanding of how cells respond to such forces is lacking. To understand the interplay between cell elasticity and its response to forces we are studying elongation of C. elegans embryos, which is initially driven by actomyosin contractility till muscle becomes active at the 1.7 fold stage, and then allow the embryo to elongate to reach 4-fold stage. Our main goal is to understand how the epidermis, an elastic material, acquires progressively its shape through cycles of muscle contractions. Previous work has positioned the kinase PAK-1 at the crossroads of hemidesmosomes and cytoskeleton remodeling. To better understand how PAK-1 acts, we performed a yeast two-hybrid screen and an RNAi screen in a strong pak-1 mutant background, which identified one factor: the a-spectrin SPC-1. We found that spc-1(-) pak-1(-) mutant embryos elongate up to the 1.5-fold stage and then retract to their initial shape. At the subcellular level, circumferential actin filament bundles appear discontinuous and not fully oriented perpendicular to the seam-dorsal junction. We performed a second RNAi enhancer screen in a spc-1(O) background and we identified three actin-binding proteins. Their absence, combined with the lack of the spectrin cytoskeleton, also induces embryos to retract. Interestingly, one of them is a formin with actin bundling properties. In a nutshell, we discovered a molecular network involved in stabilizing cell shapes in a system submitted to repeated mechanical stress. We modelled the embryo as a Kelvin-Voigt material submitted to two forces: one provided by the acto-myosin from epidermis and a second one contractile from muscles, which allowed us to predict the lengthening of the embryo over time. Altogether our data identify a cellular network that confers mechanical plasticity (in physical terms, it implies an irreversible deformation under stress) that stabilizes cell shapes during morphogenesis.

Brokate-Llanos AM et al. (2014) Mech Ageing Dev "Escherichia coli carbon source metabolism affects longevity of its predator Caenorhabditis elegans."

Garzon A, Brokate-Llanos AM, Munoz MJ

[Mech Ageing Dev, 2014]

Nutrition is probably the most determinant factor affecting aging. Microorganisms of the intestinal flora lay in the interface between available nutrients and nutrients that are finally absorbed by multicellular organisms. They participate in the processing and transformation of these nutrients in a symbiotic or commensalistic relationship. In addition, they can also be pathogens. Alive Escherichia coli OP50 are usually used to culture the bacteriovorus nematode Caenorhabditis elegans. Here, we report a beneficial effect of low concentration of saccharides on the longevity of C. elegans. This effect is only observed when the bacterium can metabolize the sugar, suggesting that physiological changes in the bacterium feeding on the saccharides are the cause of this beneficial effect.

Grewal PS (1991) Ann Appl Biol "Effects of Caenorhabditis elegans (Nematoda: Rhabditidae) on the spread of the bacterium Pseudomonas tolaasii in mushrooms (Agaricus bisporus)."

Grewal PS

[Ann Appl Biol, 1991]

The effects of mass-produced saprobic rhabditid nematodes, Caenorhabditis elegans on the spread of the bacterial blotch pathogen, Pseudomonas tolaasii, were studied in mushroom growth chambers. C. elegans significantly reduced the intensity of blotch on sporophores. Repeated isolations of the bacterial flora from the gut of C. elegans recovered from mushroom sporophores duuring cropping, revealed the presence of Pseudomonas fluorescens biovar reactans. All the isolates of P. fluorescens biovar reactans isolated from nematodes were antagonists of P. tolaasii. C. elegans produced much larger populations in monoxenic cultures with P. fluorescens biovar reactans than wit P. tolaasii. It is suggested that as C. elegans selects P. fluorescens biovar reactans rather than P. tolaasii as a food substrate it probably spreads the antagonist in the mushroom crop and may contribute to the

Chu Q et al. (2021) Sci Total Environ "Fecal microbiota transplantation attenuates nano-plastics induced toxicity in Caenorhabditis elegans."

Chu Q, Zheng X, Wang Y, Zhang S, Yu X, Zhang M

[Sci Total Environ, 2021]

Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans. Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.

Virk, Bhupinder et al. (2011) International Worm Meeting "Increasing C. elegans lifespan by inhibiting E. coli folate metabolism, but not E. coli proliferation."

Virk, Bhupinder, Weinkove, David, Dixon, David

[International Worm Meeting, 2011]

C. elegans provides an opportunity to understand how diet and microbial flora can affect lifespan. There is evidence, for example, showing that inhibition of bacterial proliferation by UV irradiation or antibiotic treatment increases C. elegans lifespan (Garigan et al, Genetics, v161, p1101 (2002)). Previously we found a spontaneous mutant of the RNAi bacteria HT115(DE3) that increases C. elegans longevity. The mutated gene aroD is involved in the shikimic acid pathway, which is responsible for producing many aromatic compounds, including the folic acid precursor para-aminobenzoic acid (PABA). Addition of PABA to aroD mutant bacteria eliminates this extended C. elegans lifespan completely, implicating folate synthesis as the cause of the lifespan increase. (Weinkove et al, unpublished) To test whether the hypothesis was also applicable in other E. coli strains including OP50 we used a sulphonamide drug, sulfamethoxazole (SMX), to inhibit bacterial folate metabolism. SMX treatment at various concentrations on OP50 bacteria increased C. elegans lifespan in a dose dependent manner. Interestingly, even though SMX is used as an antibiotic, the highest concentration used did not appear to decrease growth of the bacterial lawn substantially. This result was confirmed in liquid culture and by quantifying the cell content of bacterial lawns. Mass spectrometry was used to measure and compare folate levels in control and SMX treated OP50, and also in worms fed on these bacteria. The results show that levels of the most abundant folates in both worms and bacteria are reduced in the presence of SMX. Interestingly, we saw a greater reduction of folate in bacteria than in the worms themselves, suggesting that the worms can compensate for low folate levels in bacteria. Preliminary research suggests that SMX and kanamycin have similar effects on C. elegans lifespan, yet kanamycin kills bacteria and stops proliferation. Further work will determine whether inhibition of E. coli proliferation is necessary for the kanamycin effect. As SMX works at low concentrations and does not affect bacterial proliferation, it may be possible to use similar drugs to treat the mammalian gut flora without large changes in the microbial ecology.

Khanna A et al. (2021) Aging Cell "Trimethylamine modulates dauer formation, neurodegeneration, and lifespan through tyra-3/daf-11 signaling in Caenorhabditis elegans."

Rane A, Brem R, Kapahi P, Chamoli M, Vargas M, Peiris TH, Nelson C, Kumar J, Chinta SJ, Andersen J, Sellegounder D, Khanna A, Lithgow G

[Aging Cell, 2021]

In the nematode Caenorhabditis elegans, signals derived from bacteria in the diet, the animal's major nutrient source, can modulate both behavior and healthspan. Here we describe a dual role for trimethylamine (TMA), a human gut flora metabolite, which acts as a nutrient signal and a neurotoxin. TMA and its associated metabolites are produced by the human gut microbiome and have been suggested to serve as risk biomarkers for diabetes and cardiovascular diseases. We demonstrate that the tyramine receptor TYRA-3, a conserved G protein-coupled receptor (GPCR), is required to sense TMA and mediate its responses. TMA activates guanylyl cyclase DAF-11 signaling through TYRA-3 in amphid neurons (ASK) and ciliated neurons (BAG) to mediate food-sensing behavior. Bacterial mutants deficient in TMA production enhance dauer formation, extend lifespan, and are less preferred as a food source. Increased levels of TMA lead to neural damage in models of Parkinson's disease and shorten lifespan. Our results reveal conserved signaling pathways modulated by TMA in C. elegans that are likely to be relevant for its effects in mammalian systems.