Unravelling the mechanisms causing murepavadin resistance in : lipopolysaccharide alterations and its consequences.

Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.

Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.

Accumulation of defense systems in phage-resistant strains of .

Prokaryotes encode multiple distinct anti-phage defense systems in their genomes. However, the impact of carrying a multitude of defense systems on phage resistance remains unclear, especially in a clinical context. Using a collection of antibiotic-resistant clinical strains of and a broad panel of phages, we demonstrate that defense systems contribute substantially to defining phage host range and that overall phage resistance scales with the number of defense systems in the bacterial genome.

Regional spread of an atypical ESBL-producing ST131H89 clone among different human and environmental reservoirs in Western Switzerland.

We describe the inter-regional spread of a novel ESBL-producing subclone (ST131H89) in long-term care facility residents, general population, and environmental water sources in Western Switzerland between 2017 and 2020. The study highlights the importance of molecular surveillance for tracking emerging antibiotic-resistant pathogens in healthcare and community settings.

Prevention of Implant-Associated Infections Caused by Antibiotic-Resistant Bacteria through Biofunctionalization of Additively Manufactured Porous Titanium.

Additively manufactured (AM) porous titanium implants may have an increased risk of implant-associated infection (IAI) due to their huge internal surfaces. However, the same surface, when biofunctionalized, can be used to prevent IAI. Here, we used a rat implant infection model to evaluate the biocompatibility and infection prevention performance of AM porous titanium against bioluminescent methicillin-resistant (MRSA).

Molecular Characterization and Clinical Relevance of Taxonomic Reassignment of Staphylococcus schleiferi Subspecies into Two Separate Species, Staphylococcus schleiferi and Staphylococcus .

Staphylococcus schleiferi is an opportunistic pathogen in humans and dogs. Recent taxonomic reassignment of its subspecies ( subsp. and subsp.

With or without you? Perceived indispensability and opposition to separatist movements.

Positive intergroup relations are shown to be related to the perception that, despite mutual differences, all subgroups are indispensable for the identity or functioning of the overall society. Yet, so far, the research on identity and functional indispensability is concerned with minorities that strive for inclusion in the larger nation-state (e.g.

Clostridioides difficile infection with isolates of cryptic clade C-II: a genomic analysis of polymerase chain reaction ribotype 151.

Objectives: We report a patient case of pseudomembranous colitis associated with a monotoxin-producing Clostridioides difficile belonging to the very rarely diagnosed polymerase chain reaction (PCR) ribotype (RT) 151. To understand why this isolate was not identified using a routine commercial test, we performed a genomic analysis of RT151.

Methods: Illumina short-read sequencing was performed on n = 11 RT151s from various geographical regions to study their genomic characteristics and relatedness.

Air pollution from livestock farms and the oropharyngeal microbiome of COPD patients and controls.

Air pollution from livestock farms is known to affect respiratory health of patients with chronic obstructive pulmonary disease (COPD). The mechanisms behind this relationship, however, remain poorly understood. We hypothesise that air pollutants could influence respiratory health through modulation of the airway microbiome.

Fighting Antibiotic-Resistant Bacterial Infections by Surface Biofunctionalization of 3D-Printed Porous Titanium Implants with Reduced Graphene Oxide and Silver Nanoparticles.

Nanoparticles (NPs) have high multifunctional potential to simultaneously enhance implant osseointegration and prevent infections caused by antibiotic-resistant bacteria. Here, we present the first report on using plasma electrolytic oxidation (PEO) to incorporate different combinations of reduced graphene oxide (rGO) and silver (Ag) NPs on additively manufactured geometrically ordered volume-porous titanium implants. The rGO nanosheets were mainly embedded parallel with the PEO surfaces.

Whole-genome analysis of strains isolated from persons with cystic fibrosis.

is a commensal of the respiratory tract that is frequently present in cystic fibrosis (CF) patients and may cause infection. Antibiotic resistance is well described for CF strains, and virulence factors have been proposed. The genetic diversity of strains present in the lungs of persons with CF is largely unknown despite the fact that this organism is considered to be a pathogen in this condition.

Taxonomic position, antibiotic resistance and virulence factors of clinical isolates.

The role of species in lung disease remains unclear. The aim of this study was to characterize isolated from persons with cystic fibrosis and from other clinical samples. Whole genome sequences from 101 isolates were determined (81 from patients with cystic fibrosis and 20 from other patients) and analysed.

Taxonomic position, antibiotic resistance and virulence factor production by Stenotrophomonas isolates from patients with cystic fibrosis and other chronic respiratory infections.

Background: The potential pathogenic role of Stenotrophomonas maltophilia in lung disease and in particular in cystic fibrosis is unclear. To develop further understanding of the biology of this taxa, the taxonomic position, antibiotic resistance and virulence factors of S. maltophilia isolates from patients with chronic lung disease were studied.

Establishing Antimicrobial Susceptibility Testing Methods and Clinical Breakpoints for Inhaled Antibiotic Therapy.

Inhaled antibiotics are a common and valuable therapy for patients suffering from chronic lung infection, with this particularly well demonstrated for patients with cystic fibrosis. However, in vitro tests to predict patient response to inhaled antibiotic therapy are currently lacking. There are indications that antimicrobial susceptibility testing (AST) may have a role in guidance of therapy, but which tests would correlate best still needs to be researched in clinical studies or animal models.

Human monoclonal antibodies against surface antigens recognize in vitro and in vivo biofilm.

Implant-associated infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections.

Characterization of clinical Ralstonia strains and their taxonomic position.

To improve understanding of the role of Ralstonia in cystic fibrosis (CF), whole genomes of 18 strains from clinical samples were sequenced using Illumina technology. Sequences were analysed by core genome Multi-Locus Sequence Typing, Average Nucleotide Identity based on BLAST (ANIb), RAST annotation, and by ResFinder. Phylogenetic analysis was performed for the 16S rRNA gene, and the OXA-22 and OXA-60 ß-lactamase families.

Populations of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae are different in human-polluted environment and food items: a multicentre European study.

Objectives: To assess the extent to which food items are a source of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli (ESBL-Ec) and ESBL-producing Klebsiella pneumoniae (ESBL-Kp) for humans in five European cities.

Methods: We sampled 122 human polluted (hp)-environments (sewers and polluted rivers, as a proxy of human contamination) and 714 food items in Besançon (France), Geneva (Switzerland), Sevilla (Spain), Tübingen (Germany) and Utrecht (The Netherlands). A total of 254 ESBL-Ec and 39 ESBL-Kp isolates were cultured.

Anti-biofilm activity of murepavadin against cystic fibrosis Pseudomonas aeruginosa isolates.

Objectives: To determine the activity of murepavadin in comparison with tobramycin, colistin and aztreonam, against cystic fibrosis (CF) Pseudomonas aeruginosa isolates growing in biofilms. The biofilm-epidemiological cut-off (ECOFF) values that include intrinsic resistance mechanisms present in biofilms were estimated.

Methods: Fifty-three CF P.

Differential Analysis of Longitudinal Methicillin-Resistant Staphylococcus aureus Colonization in Relation to Microbial Shifts in the Nasal Microbiome of Neonatal Piglets.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen and often colonizes pigs. To lower the risk of MRSA transmission to humans, a reduction of MRSA prevalence and/or load in pig farms is needed. The nasal microbiome contains commensal species that may protect against MRSA colonization and may be used to develop competitive exclusion strategies.

False amoxicillin/clavulanic acid susceptibility in Bacteroides fragilis using gradient strip tests.

Background: Repeatedly, too low MIC results were obtained in Bacteroides fragilis quality assessment strains, using gradient strip tests with a ratio of amoxicillin:clavulanic acid of 2:1. We aimed to find the most accurate available gradient strip tests for susceptibility testing of amoxicillin/clavulanic acid in B. fragilis in comparison with agar dilution with EUCAST methodology and breakpoints.

Comparative genomics of ESBL-producing Escherichia coli (ESBL-Ec) reveals a similar distribution of the 10 most prevalent ESBL-Ec clones and ESBL genes among human community faecal and extra-intestinal infection isolates in the Netherlands (2014-17).

Introduction: The human gut microbiota is an important reservoir of ESBL-producing Escherichia coli (ESBL-Ec). Community surveillance studies of ESBL-Ec to monitor circulating clones and ESBL genes are logistically challenging and costly.

Objectives: To evaluate if isolates obtained in routine clinical practice can be used as an alternative to monitor the distribution of clones and ESBL genes circulating in the community.

Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients.

Objectives: This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient.

Methods: Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case.

Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates.

Background: Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations.

Behçet's Disease Under Microbiotic Surveillance? A Combined Analysis of Two Cohorts of Behçet's Disease Patients.

In Behçet's disease (BD), an auto-inflammatory vasculitis, an unbalanced gut microbiota can contribute to pro-inflammatory reactions. In separate studies, distinct pro- and anti-inflammatory bacteria associated with BD have been identified. To establish disease-associated determinants, we performed gut microbiome profiling in BD patients from the Netherlands ( = 19) and Italy ( = 13), matched healthy controls (HC) from the Netherlands ( = 17) and Italy ( = 15) and oral microbiome profiling in Dutch BD patients ( = 18) and HC ( = 15) by 16S rRNA gene sequencing.

Functionality-packed additively manufactured porous titanium implants.

The holy grail of orthopedic implant design is to ward off both aseptic and septic loosening for long enough that the implant outlives the patient. Questing this holy grail is feasible only if orthopedic biomaterials possess a long list of functionalities that enable them to discharge the onerous task of permanently replacing the native bone tissue. Here, we present a rationally designed and additive manufacturing (AM) topologically ordered porous metallic biomaterial that is made from Ti-6Al-4V using selective laser melting and packs most (if not all) of the required functionalities into a single implant.