Search bioRxiv⌕ Search

Biology subjects

Coman, C.

Publications and source records attributed to Coman, C..

7 recordsLinked to original sources

Microbial community diversity predicts invasion resistance of freshwater biofilms against antibiotic-resistant bacteria

Rivers receive continuous inputs of antibiotic-resistant bacteria (ARB) from wastewater, agriculture, and other anthropogenic sources, yet it remains unclear whether the recipient ecological component and its microbial communities determine whether introduced ARB establish or disappear. Ecological invasion theory predicts that invasion success depends on biodiversity, community stability, and occupation of ecological niche space, but these mechanisms have rarely been evaluated together in natural microbial communities. Here, we challenged river biofilms collected from 20 sites in 12 European rivers across six countries with a model antibiotic-resistant Escherichia coli carrying a conjugative IncP-1 plasmid The invasion assays were carried out under standardized laboratory flume conditions. River biofilms differed markedly in their permissiveness to invasion despite identical invasion conditions. Higher bacterial diversity consistently accelerated invader loss rates, whereas communities containing more abundant and diverse close phylogenetic neighbours of the invader exhibited stronger exclusion during early biofilm establishment. Diversity loss during transition into the experimental system emerged as the strongest explanatory variable of invasion resistance prior to biofilm maturation, whereas Shannon diversity became the dominant predictor in mature communities. Integrating these complementary ecological dimensions substantially improved explanatory prediction of ARB persistence compared with individual predictors alone. Particularly invasion-resistant biofilms also exhibited distinct ecological community composition consistent with mature, structurally complex microbial assemblages. Together, our findings demonstrate that the establishment of ARB in the environment is not stochastic but can be predicted from measurable ecological properties of recipient microbiomes, highlighting microbial biodiversity and community organization as natural barriers to antimicrobial resistance dissemination.

microbiology↗

ER-Lysosome Cholesterol Exchange Regulates Lysosomal Motility Through mTOR-Dependent LAMTOR1 Phosphorylation

The subcellular distribution of lysosomes, the main degradative organelles of mammalian cells, responds to metabolic cues in a highly dynamic way. While lysosomal positioning due to amino acid levels is well-characterized, cholesterol-dependent regulation of lysosomal motility is incompletely understood. We explored impaired lysosomal cholesterol export using a mass spectrometry-based multi-OMICs approach, identifying widespread reallocation of resources and signaling pathway modulation. We identified increased phosphorylation at LAMTOR1 serine 56 in response to cholesterol level perturbations. We demonstrate that this phosphorylation site is sufficient to disrupt Rag GTPases/SLC38A9 binding to the Ragulator complex, inhibiting canonical mTORC1 and facilitating binding of BORC, therefore promoting lysosomal retrograde movement. LAMTOR1 S56 phosphorylation responds exclusively to depletion of lysosomal limiting membrane cholesterol, is facilitated by mTOR, and presents a negative feedback loop for amino acid independent displacement of Ragulator bound Rag GTPases, limiting canonical mTORC1 activity. Mass spectrometry data are available via ProteomeXchange with identifier PXD073489. HighlightsO_LIPerturbation of lysosomal cholesterol homeostasis results in adaptation of cellular protein and lipid biosynthesis C_LIO_LILAMTOR1 is phosphorylated at serine 56 via mTORC1 C_LIO_LILAMTOR1 S56 phosphorylation is lysosomal membrane cholesterol dependent C_LIO_LILAMTOR1 S56 phosphorylation disrupts binding of Rag GTPases to the Ragulator complex C_LIO_LILAMTOR1 S56 phosphorylation promotes binding of Ragulator to BORC, facilitating lysosomal retrograde transport C_LI

molecular biology↗

Dynamic neutrophil lipidome remodeling during induction of NETosis

Neutrophil Extracellular Trap formation (NETosis) affects a wide variety of clinically relevant human diseases. Although lipid remodeling is essential for neutrophil function and membrane rupture during NETosis, the neutrophil lipidome and its dynamics have not been characterized. Thus, we establish the first quantitative lipidome of human neutrophils comprising 1,039 species across nine orders of magnitude and map its remodeling during NETosis. NET formation caused profound alterations in the phosphatidylinositol, phosphatidic acid, diacylglycerol and lysoglycerophospholipid levels. Calcium- and reactive oxygen species-dependent NETosis pathways displayed distinct lipidomic trajectories, yet converged on the significance of phospholipid lipase networks. Pharmacological inhibition of this networks altered lipid composition and markedly impaired NETosis, while diacylglycerol (DG) treatment revoked the effect. Altogether our findings reveal lipid remodeling as a fundamental determinant of NETosis and identify interconnected and dependent phospholipid lipase networks with downstream DG-dependent signaling as a potential therapeutic target in NET-associated diseases.

molecular biology↗

GPR27 mediates adrenergic ligands-induced transinhibition of EGFR

1.G-protein coupled receptor 27 (GPR27) is part of the "Super Conserved Receptors Expressed in Brain" (SREB) family, alongside GPR85 and GPR173. While the endogenous ligands and functions of SREB receptors are still unknown, GPR27 has been implicated in insulin secretion and tumorigenesis. Here, we show that substituting GPR27s C-terminus domain with that of the {beta}1 adrenergic receptor ({beta}1AR) yields a chimera with {beta}1AR-like ligand selectivity and cellular functions. Interestingly, adrenergic ligands stimulation of GPR27 inhibited EGF-induced serum-responsive element (SRE) activation, independently of G-proteins and {beta}-arrestins, through dephosphorylation of c-Src and EGFR proteins. This unique response was exclusive to GPR27, as GPR85 and GPR173 showed no similar effects. These findings suggest that GPR27 is a receptor responding to adrenergic ligands to transinhibit EGFR through an atypical signaling mechanism.

cell biology↗

Adenosine signaling in glia modulates metabolic state-dependent behavior in Drosophila

An animals metabolic state strongly influences its behavior. Hungry animals prioritize food seeking and feeding behaviors, while sated animals suppress these behaviors to engage in other activities. Additionally, neuronal activity and synaptic transmission are among the most energy expensive processes. Yet neurons do not uptake nutrients from the circulation. Instead, glia fulfill this highly evolutionary conserved function. Recent studies have shown that glia can modulate neuronal activity and behavior. However, how different glia subtypes sense metabolic state and modulate neurons and behavior is incompletely understood. Here, we unravel two types of glia-mediated modulation of metabolic state-dependent behavior. In food-deprived flies, astrocyte-like and perineurial glia promote foraging and feeding, respectively, while cortex glia suppress these behaviors. We further show that adenosine and adenosine receptor modulate intracellular calcium levels in these glia subtypes, which ultimately controls behavior. This study reveals a new mechanism how different glia subtypes sense the metabolic state of the animal and modulate its behavior accordingly.

neuroscience↗

Tradeoffs of increasing temperatures for the spread of antimicrobial resistance in river biofilms

River microbial communities regularly act as the first defense barrier against the spread of antimicrobial resistance genes (ARG) that enter environmental microbiomes through wastewaters. However, how the invasion dynamics of wastewater-born ARGs into river biofilm communities will shift due to increasing average and peak temperatures worldwide through climate change remains unknown. Here we aimed at elucidating the effects of increasing temperatures on both, the natural river biofilm resistome, as well as the river biofilms invadability by foreign, wastewater-born ARGs. To achieve this, natural biofilms were grown in a pristine German river and transferred to artificial laboratory recirculation flume systems at three different temperatures (20{degrees}C, 25{degrees}C, 30{degrees}C). Already after one week of acclimatization to the temperatures, significant increases in the abundance of most naturally occurring ARGs were detected in the biofilms exposed to the highest temperature. Thereafter, biofilms were exposed to a single pulse of wastewater and the invasion dynamics of wastewater-born ARGs were analyzed over a period of two weeks. While initially after one day ARGs were able to invade all biofilms successfully and in equal proportions, the foreign invading ARGs were lost at a far increased rate at 30{degrees}C over time. ARG levels dropped to the initial natural levels at 30{degrees}C after 14 days. Contrary at the lower temperatures ARGs remained far elevated and certain ARGs were able to establish themselves in the biofilms. Overall, we here demonstrate tradeoffs of increasing temperature between increases in naturally occurring and faster loss dynamics of invading ARGs.

microbiology↗

Microbiome diversity: A barrier to the environmental spread of antimicrobial resistance?

BackgroundIn the environment, microbial communities are constantly exposed to invasion by antimicrobial resistant bacteria (ARB) and their associated antimicrobial resistance genes (ARGs) that were enriched in the anthroposphere. A successful invader has to overcome the biotic resilience of the habitat, which is more difficult with increasing biodiversity. The capacity to exploit resources in a given habitat is enhanced when communities exhibit greater diversity, reducing opportunities for invaders, leading to a lower persistence. In the context of antimicrobial resistance (AMR) dissemination, exogenous ARB reaching a natural community may persist longer if the biodiversity of the autochthonous community is low, increasing the chance of ARGs to transfer to community members. Reciprocally, high microbial diversity could serve as a natural long-term barrier towards invasion by ARB and ARGs. ResultsTo test this hypothesis, a sampling campaign across seven European countries was carried out to obtain 172 environmental samples from sites with low anthropogenic impact. Samples were collected from contrasting environments: stationary structured forest soils, or dynamic river biofilms and sediments. Microbial diversity and relative abundance of 27 ARGs and 5 mobile genetic element marker genes were determined. In soils, higher diversity, evenness and richness were all significantly negatively correlated with the relative abundance of the majority (>85%) of ARGs. Furthermore, the number of detected ARGs per sample was inversely correlated with diversity. However, no such effects were found for the more dynamic, regularly mixed rivers. Conclusions: In conclusion, we demonstrate that diversity can serve as barrier towards AMR dissemination in the environment. This effect is mainly observed in stationary, structured environments, where long-term, diversity-based resilience against invasion can evolve. Such barrier effects can in the future be exploited to limit the environmental proliferation of AMR.

microbiology↗