Staphylococcus epidermidis surface protein I (SesI) : a marker of the invasive capacity of S. epidermidis?

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Highly Functionalized <i>tertiary-</i>Carbinols and Carbinamines from the Asymmetric γ‑Alkoxyallylboration of Ketones and Ketimines with the Borabicyclodecanes

The first asymmetric γ-alkoxy­allyl­boration of representative ketones provides β-alkoxy <i>tert</i>-homoallylic alcohols <b>10</b> whose diastereoselectivities range from 99% <i>syn</i> (acetophenone) to 99% <i>anti</i> (pinacolone) both with high ee (>95%). This distribution is attributable to the <i>c</i>/<i>t</i> isomerization of the BBD reagents and the greater reactivity of <b>7</b> vs <b>1</b> and of aromatic vs alkyl ketones. A ketone-based direct synthesis of a fostriecin intermediate and the <i>tert</i>-amine <b>26</b> are reported, each with high selectivities

β-lactamase-mediated Resistance in MDR-Pseudomonas Aeruginosa from Qatar

Abstract Background: Anti-pseudomonal b-lactam antibiotics are of paramount importance in the management of Pseudomonas aeruginosa infections. The distribution of b-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. In the present study whole-genome sequencing (WGS) was used to identify the predominant sequence types (STs) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD PhoenixTM system and manual Liofilchem MIC Test Strips. Seventy-five MDR-P. aeruginosa isolates were subsequently processed for WGS. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.33%). Almost all isolates possessed Class C and Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.67%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. The most frequent sequence types identified were ST235 (n=16, 21.33%), ST357 (n=8, 10.67%), ST389 and ST1284 (6, 8% each). Nearly all ST235 (15/16; 93.75%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. Global high-risk STs are predominant in Qatar and their associated multi-resistant phenotypes are a cause for considerable concern. The molecular epidemiology trends of P. aeruginosa should be surveillance at national levels to track their trends and institute the appropriate control strategies.</jats:p

β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar

Abstract Background: The distribution of b-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD PhoenixTM system and manual Liofilchem MIC Test Strips. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.3%). All isolates possessed Class C and/or Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. High risk ST235 (n=16, 21.3%), ST357 (n=8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.</jats:p

β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar

Abstract Background: The distribution of b-lactamase resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD Phoenix system and manual Liofilchem MIC Test Strips. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.3%). Almost all isolates possessed Class C and Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. High risk ST235 (n=16, 21.3%), ST357 (n=8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.</jats:p

Plantaricin NC8 alpha beta exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics

The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 alpha beta were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 alpha and beta were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 alpha beta caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, beta 1-22, beta 7-34 and beta 1-20 retained an inhibitory activity. The peptides diffused rapidly (2min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 alpha beta substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 alpha beta is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.Funding Agencies|Foundation of Magnus Bergvalls [2015-00823]; Knowledge Foundation [20150244, 20150086]; Swedish Research CouncilSwedish Research Council [2016-04874, 2017-04475]; Swedish Cancer SocietySwedish Cancer Society [17 0532]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [RMX18-0039]; orebro University</p

Clinical outcomes, molecular epidemiology and resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa isolated from bloodstream infections from Qatar

Background Bloodstream infections (BSIs) caused by multidrug-resistant (MDR)-Pseudomonas aeruginosa are associated with poor clinical outcomes, at least partly due to delayed appropriate antimicrobial therapy. The characteristics of MDR-P. aeruginosa bloodstream isolates have not been evaluated in Qatar. Our study aimed to examine in vitro susceptibility, clinical and molecular characteristics, and mechanisms of resistance of MDR-P. aeruginosa bloodstream isolates from Qatar.Materials and methods We included all MDR-P. aeruginosa isolated from blood cultures taken between October 2014 and September 2017. Blood cultures were processed using BD BACTEC™ FX automated system. BD Phoenix™ was used for identification, Liofilchem® MIC Test Strips for MIC determination. Whole-genome sequencing was performed using the Illumina-HiSeq-2000.Results Out of 362 P. aeruginosa bloodstream isolates, 16 (4.4%) were MDR. The median patient age was 55 years (range 43–81) and all patients presented with septic shock. Most patients received meropenem (12/16) and/or colistin (10/16). Clinical response was achieved in eight patients, and five patients died within 30-days. MDR-P. aeruginosa isolates belonged to 13 different sequence types. All isolates were non-susceptible to cefepime and ciprofloxacin. The most active agents were colistin (16/16) and aztreonam (10/16). Seven isolates produced blaVIM, and four possessed genes encoding extended-spectrum β-lactamases. Aminoglycoside modifying enzymes were present in 15/16, transferable qnr-mediated quinolone resistance gene was detected in 3/16, and the novel ciprofloxacin modifying enzyme CrpP-encoding gene in one isolate.Conclusion MDR-P. aeruginosa BSIs are relatively uncommon in Qatar but are highly resistant, harbour multiple resistance genes, and are commonly associated with unfavourable clinical outcomes. Colistin was the only agent with consistent activity against the study isolates.Key messagesMDR-P. aeruginosa constituted <5% of P. aeruginosa blood isolates over three years.Typical risk factors for MDR infections were highly prevalent in the study population and overall clinical outcomes are consistent with those previously reported.Colistin was the only agent with consistent antibacterial activity against the study isolates