Rôle d'une D,D-carboxypeptidase dans une nouvelle voie de synthèse du peptidoglycane chez Enterococcus faecium résistant à l'ampicilline

Chez Enterococcus faecium, un mutant résisant à l'ampicliline a été obtenu après cinq étapes de sélection sur des concentrations croissantes d'ampiciline. Un nouverau type de pontage du peptidoglycane a été mis en évidence. La voie classique par D,D-transpeptidation (PLP), sensible à l'ampiciline, a été remplacé par une L,D-transpeptidation. Des activités D,D-carboxypeptidases et L,D-transpeptidase, insensibles aux b-lactalines, ont été détectées. L'activité de D,D-carboxypeptidase pourrait générer le substrat tétrapeptidique de la L,D-transpeptidase. Dans le génome de E. faecium, nous avons identifié deux gènes (Y1 et Y2) codant pour des protéines apparentées aux métallo-D,D-carboxypeptidases . Le gène Y2 appartient à un locus composé d'un système de régulation à deux composants (senseur et régulateur). Nous avons mis en evidence une mutation dans le senseur chez le mutant hautement résistant. Les D,D-carboxypeptidases, insensibles aux b-lactamines, apparaissent comme des enzymes clés dans l'expression de cette nouvelle voie de synthèse du peptidoglycane.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

How Did We End Up Using a Quadruple Guided Therapy Combining At Least Two Antibiotics with a PPI to Eradicate Helicobacter pylori?

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Epidémiologie nationale française des surinfections bactériennes dans les pneumonies acquises sous ventilation mécanique chez les patients infectés par COVID-19 : l'étude COVAP

International audienceBackground Description and comparison of bacterial characteristics of ventilator-associated pneumonia (VAP) between critically ill intensive care unit (ICU) patients with COVID-19-positive, COVID + ; and non-COVID-19, COVID-. Methods Retrospective, observational, multicenter study that focused on French patients during the first wave of the pandemic (March-April 2020). Results 935 patients with identification of at least one bacteriologically proven VAP were included (including 802 COVID +). Among Gram-positive bacteria, S. aureus accounted for more than two-thirds of the bacteria involved, followed by Streptococcaceae and enterococci without difference between clinical groups regarding antibiotic resistance. Among Gram-negative bacteria, Klebsiella spp. was the most frequently observed bacterial genus in both groups, with K. oxytoca overrepresented in the COVID-group (14.3% vs. 5.3%; p < 0.05). Cotrimoxazole-resistant bacteria were over-observed in the COVID + group (18.5% vs. 6.1%; p <0.05), and after stratification for K. pneumoniae (39.6% vs. 0%; p <0.05). In contrast, overrepresentation of aminoglycoside-resistant strains was observed in the COVIDgroup (20% vs. 13.9%; p < 0.01). Pseudomonas sp. was more frequently isolated from COVID + VAPs (23.9% vs. 16.7%; p <0.01) but in COVID-showed more carbapenem resistance (11.1% vs. 0.8%; p <0.05) and greater resistance to at least two aminoglycosides (11.8% vs. 1.4%; p < 0.05) and to quinolones (53.6% vs. 7.0%; p <0.05). These patients were more frequently infected with multidrug-resistant bacteria than COVID + (40.1% vs. 13.8%; p < 0.01). Conclusions The present study demonstrated that the bacterial epidemiology and antibiotic resistance of VAP in COVID + is different from that of COVID-patients. These features call for further study to tailor antibiotic therapies in VAP patients.Contexte Description et comparaison des caractéristiques bactériennes des pneumonies acquises sous ventilation mécanique (PAV) entre des patients en unité de soins intensifs (USI) gravement malades avec COVID-19 positif, COVID + ; et non COVID-19, COVID-. Méthodes Étude rétrospective, observationnelle, multicentrique, centrée sur les patients français lors de la première vague de la pandémie (mars-avril 2020). Résultats 935 patients avec identification d'au moins une PVA bactériologiquement prouvée ont été inclus (dont 802 COVID +). Parmi les bactéries à Gram positif, S. aureus représentait plus des deux tiers des bactéries impliquées, suivi des Streptococcaceae et des entérocoques sans différence entre les groupes cliniques concernant la résistance aux antibiotiques. Parmi les bactéries à Gram négatif, Klebsiella spp. était le genre bactérien le plus fréquemment observé dans les deux groupes, avec une surreprésentation de K. oxytoca dans le groupe COVID (14,3 % contre 5,3 % ; p < 0,05). Les bactéries résistantes au cotrimoxazole ont été sur-observées dans le groupe COVID + (18,5 % vs. 6,1 % ; p <0,05), et après stratification pour K. pneumoniae (39,6 % vs. 0 % ; p <0,05). En revanche, une surreprésentation des souches résistantes aux aminosides a été observée dans le groupe COVID (20 % contre 13,9 % ; p < 0,01). Pseudomonas sp. a été plus fréquemment isolé dans les PVA COVID + (23,9 % vs. 16,7 % ; p <0,01), mais dans le groupe COVID, on a observé une plus grande résistance aux carbapénèmes (11,1 % vs. 0,8 % ; p <0,05) et une plus grande résistance à au moins deux aminosides (11,8 % vs. 1,4 % ; p <0,05) et aux quinolones (53,6 % vs. 7,0 % ; p <0,05). Ces patients étaient plus fréquemment infectés par des bactéries multirésistantes que les patients COVID + (40,1 % contre 13,8 % ; p < 0,01). Conclusions La présente étude a démontré que l'épidémiologie bactérienne et la résistance aux antibiotiques de la PVA chez les patients COVID + sont différentes de celles des patients COVID. Ces caractéristiques appellent à des études plus approfondies afin d'adapter les traitements antibiotiques aux patients atteints de PVA

Distribution of Spontaneous gyrA Mutations in 97 Fluoroquinolone-Resistant Helicobacter pylori Isolates Collected in France

We determined the prevalence of gyrA mutations conferring fluoroquinolone resistance in 97 Helicobacter pylori isolates collected in France from 2007 to 2010. Ninety-four harbored one or two mutations already found in the quinolone resistance determining region (QRDR) of gyrA (for T87I, n = 23; for N87K, n = 32; for D91N, n = 30; for D91G, n = 7; for D91Y, n = 6), 2 harbored a mutation never previously described (D91H and A88P), and one strain was resistant (ciprofloxacin MIC of 8 mg/liter) without a detected mutation conferring this resistance in gyrA or gyrB genes

The First Lethal Infection by <i>Oligella ureolytica</i>: A Case Report and Review of the Literature

Oligella ureolytica is a Gram-negative bacillus, a member of the Alcaligenaceae family, that had never previously been reported as lethal. Herein, a case of fatal infection caused by Oligella ureolytica in an elderly woman with suspected bladder cancer is reported. The species identification was confirmed through Sanger sequencing of the bacterial 16S rRNA sequence and compared to published sequences for phylogenetic analysis. Initial antibiotic therapy with ceftriaxone and oxacillin was initiated but had to be switched due to resistance. Cefepime in combination with metronidazole was administered, unfortunately failing to prevent the patient’s death. Further studies are needed to explore additional factors influencing clinical outcomes in Oligella ureolytica infections

K1 Antigen Is Associated with Different AST Profile in Escherichia coli: A One-Month-Long Pilot Study

International audienceEscherichia coli is responsible for diseases of varying severity. The “K” antigen designates the capsular polysaccharides on the bacterial surface, which are mostly similar to those of highly pathogenic bacteria. The K1 antigen is often found in pathogenic E. coli. Aim: While the published studies on the AST profile of K1-positive E. coli have focused on pregnant women or newborns, this study aimed to characterize the AST profile of K1-positive E. coli independently of the clinical sample of isolation. Over a 4-week-long period, all patients hospitalized/consulting at the Poitiers University Hospital presenting a determined AST on E. coli were prospectively included to define their K1-status (Pastorex Meningitis) and to collect the clinical (age/sex) or biological metadata (AST/MIC). Among the 296 included samples, no differential representation was observed between K1 results regarding sample nature. K1-negative results were associated with multiple antibiotic-resistance (12.3% vs. 33.0%; p < 0.01). AST phenotypes differed between these groups, with a higher proportion of K1-negativity among resistant strains, especially on β-lactams (ureidopenicillin, 25.8% vs. 14.9%; and ampicillin/inhibitor, 50.0% vs. 26.8%; p < 0.05) or quinolone (19.8% vs. 7.0%) and sulfamethoxazole-trimethoprim (30.2% vs. 12.3%) (p < 0.01). This study analyzed E. coli ASTs in clinical samples of all types, regarding their K1-antigen status

Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study

International audienceBackground: The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France.Methods: We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples.Findings: We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older.Interpretation: PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines.Funding: Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci

Novel mechanism of resistance to glycopeptide antibiotics in Enterococcus faecium.

International audienceGlycopeptides and beta-lactams are the major antibiotics available for the treatment of infections due to Gram-positive bacteria. Emergence of cross-resistance to these drugs by a single mechanism has been considered as unlikely because they inhibit peptidoglycan polymerization by different mechanisms. The glycopeptides bind to the peptidyl-D-Ala(4)-D-Ala(5) extremity of peptidoglycan precursors and block by steric hindrance the essential glycosyltransferase and D,D-transpeptidase activities of the penicillin-binding proteins (PBPs). The beta-lactams are structural analogues of D-Ala(4)-D-Ala(5) and act as suicide substrates of the D,D-transpeptidase module of the PBPs. Here we have shown that bypass of the PBPs by the recently described beta-lactam-insensitive L,D-transpeptidase from Enterococcus faecium (Ldt(fm)) can lead to high level resistance to glycopeptides and beta-lactams. Cross-resistance was selected by glycopeptides alone or serially by beta-lactams and glycopeptides. In the corresponding mutants, UDP-MurNAc-pentapeptide was extensively converted to UDP-MurNAc-tetrapeptide following hydrolysis of D-Ala(5), thereby providing the substrate of Ldt(fm). Complete elimination of D-Ala(5), a residue essential for glycopeptide binding, was possible because Ldt(fm) uses the energy of the L-Lys(3)-D-Ala(4) peptide bond for cross-link formation in contrast to PBPs, which use the energy of the D-Ala(4)-D-Ala(5) bond. This novel mechanism of glycopeptide resistance was unrelated to the previously identified replacement of D-Ala(5) by D-Ser or D-lactate

Th-17 response and antimicrobial peptide expression are uniformly expressed in gastric mucosa of Helicobacter pylori -infected patients independently of their clinical outcomes

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Phenol-soluble modulins α are major virulence factors of <i>Staphylococcus aureus</i> secretome promoting inflammatory response in human epidermis

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