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Fortin, C.

Publications and source records attributed to Fortin, C..

3 recordsLinked to original sources

New sensitive tools to characterize meta-metabolome response to short- and long-term cobalt exposure in dynamic river biofilm communities

Untargeted metabolomics is a non-a priori analysis of biomolecules that characterizes the metabolome variations induced by short- and long-term exposures to stressors. Even if the metabolite annotation remains lacunar due to database gaps, the global metabolomic fingerprint allows for trend analyses of dose-response curves for hundreds of cellular metabolites. The combination of untargeted metabolomic features and benchmark-dose (BMD) calculations then makes it possible to determine concentration range inducing defense responses (CRIDeR) and concentration range inducing damage responses (CRIDaR). To develop this approach in a context of time-dependent microbial community changes, mature river biofilms were exposed for 1 month to four cobalt (Co) concentrations (background concentration, 1 x 10-7, 5 x 10-7 and 1 x 10- 6 M) in an open system of artificial streams. The meta-metabolomic response of biofilms was compared against a multitude of biological parameters (including bioaccumulation, biomass, chlorophyll a content, composition and structure of prokaryotic and eukaryotic communities) monitored at set exposure times (from 1 hour to 28 days). Cobalt exposure induced extremely rapid responses of the meta-metabolome, with time range inducing defense responses (TRIDeR) of around ten seconds, and time range inducing damage responses (TRIDaR) of several hours. Even in biofilms whose structure had been altered by Co bioaccumulation (reduced biomass, chlorophyll a contents and changes in the composition and diversity of prokaryotic and eukaryotic communities), CRIDeRs with similar initiation thresholds (1.41 {+/-} 0.77 x 10-10 M Co2+ added in the exposure medium) were set up at the meta-metabolome level at every time point. In contrast, the CRIDaR initiation thresholds increased by 10 times in long-term Co exposed biofilms. The present study demonstrates that defense and damage responses of biofilm meta-metabolome exposed to Co are rapidly and sustainably impacted, even within tolerant and resistant microbial communities. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/567369v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@e7a87eorg.highwire.dtl.DTLVardef@e712b7org.highwire.dtl.DTLVardef@7de128org.highwire.dtl.DTLVardef@493053_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIProkaryotic community structures were impacted after 1 h of exposure to Co C_LIO_LIBiofilm meta-metabolome was impacted after 36 s of exposure to Co C_LIO_LIBiofilm meta-metabolome response was faster than changes in biofilm communities C_LIO_LIShort- and long-term exposed biofilms have similar CRIDeR initiation thresholds C_LIO_LILong-term exposed biofilms have higher CRIDaR initiation thresholds C_LI

molecular biology↗

Meta-metabolomic Responses of River Biofilms to Cobalt Exposure and Use of Dose-response Model Trends as an Indicator of Effects

Metabolites are low molecular-weight molecules produced during cellular metabolism. The global expression of the meta-metabolome (metabolomics at the community level) could thus potentially be used to characterize the exposure of an organism or a community to a specific stressor. Here, the meta-metabolomic fingerprints of mature biofilms were examined after 1, 3 and 7 days of exposure to five concentrations of cobalt (0, 1 x 10-7, 1 x 10-6, 5 x 10-6 and 1 x 10-5 M) in aquatic microcosms. The global changes in meta-metabolomic fingerprints were in good agreement with those of the other biological parameters studied (cobalt bioaccumulation, biomass, chlorophyll content). To better understand the dose-responses of the biofilm meta-metabolome, the untargeted LC-HRMS metabolomic data were further processed using the DRomics tool to build dose-response model curves and to calculate benchmark doses (BMD). These BMDs were aggregated into an empirical cumulative density function. A trend analysis of the metabolite dose-response curves suggests the presence of a concentration range inducing defense mechanisms (CRIDeM) between 4.7 x 10-7 and 2.7 x 10-6 M, and of a concentration range inducing damage mechanisms (CRIDaM) from 2.7 x 10-6 M to the highest Co concentration. The present study demonstrates that the molecular defense and damage mechanisms can be related to contaminant concentrations and represent a promising approach for environmental risk assessment of metals. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/545533v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@179fd06org.highwire.dtl.DTLVardef@1d2cd10org.highwire.dtl.DTLVardef@9508a3org.highwire.dtl.DTLVardef@6a1818_HPS_FORMAT_FIGEXP M_FIG C_FIG SYNOPSISThis study focuses on the interpretation of the metabolite dose-response trends in river biofilms exposed to cobalt to identify concentration range inducing cellular mechanisms and improve the environmental risk assessment of metals.

microbiology↗

Covid-19 vaccine immunogenicity in people living with HIV-1

IntroductionCOVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals. MethodsHIV-positive individuals (n=121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naive to SARS CoV-2 was used. The participants Anti-RBD IgG responses were measured by ELISA at baseline and 3 to 4 weeks after receiving the first dose of an mRNA vaccine). ResultsEleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between between the HIV negative control group (n=20) and the combined HIV+ group (n=106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm3. (p<0.0001). Increasing age was independently associated with decreased immunogenicity. ConclusionHIV-positive individuals with CD4 counts over 250 cells/mm3 have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm3) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose.

immunology↗