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About 25% of severe failures are caused by drugs. This particular susceptibility of the kidney can be explained by the importance of phenomenons such as glomerular filtration, reabsorption and concentration of toxins in the proximal tubular cells.
Aminoglycosides are important to consider in this context, as about 10 % of the treated patients show signs of renal toxicity. These antibiotics enter the renal cell by binding to negatively-charged phospholipids of the brush border membrane (Sastrasinh et al, 1982) and to megalin, a transmembrane protein (Moestrup et al, 1995). Some authors (Humes, 1986 ; Ishikawa et al, 1985) suggest that calcium could decrease this binding. Once internalized, aminoglycosides accumulate in lysosomes (Beauchamps et al, 1990). Their interaction with the negative-charged phospholipids inhibits the catabolism of phospholipids and induces a lysosomial phospholipidosis that might be responsible for the renal toxicity and necrosis observed (Laurent et al, 1990). At low doses, aminoglycosides can induce apoptosis (El Mouedden et al, 2000).
There are a lot of studies concerning the interactions between drugs and nutriment. Nutriments might be used as adjuvant to drugs in the future. The aim of our work is to study the interaction between calcium and aminoglycosides. More precisely we have investigated whether, in renal cultured cells (LLCPK1) treated with gentamicin, the association of gentamicin plus calcium would decrease gentamicin-induced apoptosis.
Our results show that the number of apoptotics cells increases with the concentration of gentamicin used (1, 1.5 or 2 mM) but that coincubation with calcium, whatever the concentration used (1.8, 2.25 or 3 mM), does not protect against the apoptosis induced by aminoglycosides. These results are to be related with the lack of calcium effect on gentamicin intracellular concentration Près du quart des insuffisances rénales aigües sont d’origine médicamenteuse. Cette susceptibilité particulière du rein s’explique par l’importance des phénomènes de filtration glomérulaire, de réabsorption et de concentration des toxiques au niveau tubulaire proximal. Les aminoglycosides sont particulièrement importants dans ce cadre puisque environ 10% des patients traités avec ces antibiotiques montrent des signes de toxicité rénale. Ces antibiotiques pénètrent dans la cellule rénale en se liant au niveau de la bordure en brosse aux phospholipides anioniques (Sastrasinh et al, 1982) et à une protéine transmembranaire, la mégaline (Moestrup et al, 1995). De nombreux auteurs (Humes, 1986 ; Ishikawa et al., 1985) suggèrent que le calcium pourrait diminuer cette liaison. Après internalisation, les aminoglycosides s’accumulent dans le compartiment lysosomial (Beauchamps et al, 1990). Leur interaction avec les phospholipides chargés négativement inhibe le catabolisme des phospholipides et mène au développement d’une phospholipidose lysosomiale probablement responsable de la nécrose et de la toxicité rénale observée (Laurent et al, 1990). A faibles doses, les aminoglycosides peuvent induire un phénomène d’apoptose (El Mouedden et al, 2000).
de nombreuses études s’intéressent aux interactions médicament – aliment. Les aliments pourraient être, dans le futur, utilisés comme adjuvant aux traitements médicamenteux. Dans notre étude nous nous sommes intéressés à l’interaction calcium et aminoglycoside. Dans ce contexte, le but de notre mémoire était de savoir si dans les cellules rénales (LLCPK1) traitées avec un aminoglycoside (gentamicine), l’association de cet aminoglycoside avec le calcium pourrait diminuer le processus d’apoptose, signe précoce de la toxicité induite par cet antibiotique.
nos résultats montrent que le nombre de cellules apoptotiques augmente avec la concentration en gentamicine utilisée (1, 1.5, 2 mM) mais que, quelle que soit la concentration en calcium choisie (1.8 ; 2.25 ou 3 mM) l’apoptose induite par les aminoglycosides ne diminue pas. Ces résultats sont à mettre en relation avec l’absence d’effet du calcium (1.8 ou 3 mM) sur l’accumulation intracellulaire de la gentamicine.

Calcium --- Apoptosis --- Antibiotics, Aminoglycoside

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Aminoglycosides. --- Anti-Bacterial Agents. --- Amino Sugars --- Anti-Bacterial Agents --- Aminoglycosides --- Therapeutic use. --- Anti-Bacterial Compounds --- Anti-Mycobacterial Agents --- Antibacterial Agents --- Antibiotic --- Antimycobacterial Agents --- Bacteriocidal Agents --- Bacteriocides --- Antibiotics --- Agents, Anti-Bacterial --- Agents, Anti-Mycobacterial --- Agents, Antibacterial --- Agents, Antimycobacterial --- Agents, Bacteriocidal --- Anti Bacterial Agents --- Anti Bacterial Compounds --- Anti Mycobacterial Agents --- Compounds, Anti-Bacterial --- Anti-Bacterial Agent --- Anti-Bacterial Compound --- Anti-Mycobacterial Agent --- Antibacterial Agent --- Antimycobacterial Agent --- Bacteriocidal Agent --- Bacteriocide --- Agent, Anti-Bacterial --- Agent, Anti-Mycobacterial --- Agent, Antibacterial --- Agent, Antimycobacterial --- Agent, Bacteriocidal --- Anti Bacterial Agent --- Anti Bacterial Compound --- Anti Mycobacterial Agent --- Compound, Anti-Bacterial --- Aminoglycoside

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The worldwide dissemination of antimicrobial-resistant bacteria, particularly those resistant to last-resource antibiotics, is a common problem to which no immediate solution is foreseen. In 2017, the World Health Organization (WHO) published a list of antimicrobial-resistant "priority pathogens", which include a group of microorganisms with high-level resistance to multiple drugs, named ESKAPE pathogens, comprising vancomycin-resistant Enterococcus faecium (VRE), methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA), extended spectrum β-lactamase (ESBL) or carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa and extended spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacter spp. These bacteria also have the ability to produce several virulence factors, which have a major influence on the outcomes of infectious diseases. Bacterial resistance and virulence are interrelated, since antibiotics pressure may influence bacterial virulence gene expression and, consequently, infection pathogenesis. Additionally, some virulence factors contribute to an increased resistance ability, as observed in biofilm-producing strains. The surveillance of important resistant and virulent clones and associated mobile genetic elements is essential to decision making in terms of mitigation measures to be applied for the prevention of such infections in both human and veterinary medicine, being also relevant to address the role of natural environments as important components of the dissemination cycle of these strains.

biocide --- antibiotic resistance --- cross-resistance --- aminoglycoside --- adaptation --- biofilm --- pyruvate cycle --- mastitis --- staphylococci --- virulence factors --- genes --- antimicrobial resistance --- infant --- newborn --- bacteremia --- Gram-negative bacteria --- drug resistance --- microbial --- mortality --- microcosm --- Aeromonas --- climate change --- temperature --- pH --- water --- Acinetobacter baumannii --- virulence --- whole-genome sequencing --- international high-risk clones --- genomic epidemiology --- dogs --- Escherichia coli --- ESBL --- CTX-M-15 --- CTX-M-1 --- CTX-M-32 --- CTX-M-55 --- CTX-M-14 --- qAmpC --- CMY-2 --- camel --- domestic --- milk --- virulence genes --- extended-spectrum β-lactamases --- biofilm formation --- Pseudomonas aeruginosa --- carbapenem resistance --- KPC-2 --- plasmid --- diabetic foot infections --- Staphylococcus aureus --- subinhibitory concentrations --- virulence-related genes