Prognostic Value of Gut Microbiome for Conversion from Mild Cognitive Impairment to Alzheimer's Disease Dementia within 4 Years: Results from the AlzBiom Study.

Alterations in the gut microbiome are associated with the pathogenesis of Alzheimer's disease (AD) and can be used as a diagnostic measure. However, longitudinal data of the gut microbiome and knowledge about its prognostic significance for the development and progression of AD are limited. The aim of the present study was to develop a reliable predictive model based on gut microbiome data for AD development.

Signature of Alzheimer's Disease in Intestinal Microbiome: Results From the AlzBiom Study.

Background: Changes in intestinal microbiome composition have been described in animal models of Alzheimer's disease (AD) and AD patients. Here we investigated how well taxonomic and functional intestinal microbiome data and their combination with clinical data can be used to discriminate between amyloid-positive AD patients and cognitively healthy elderly controls.

Methods: In the present study we investigated intestinal microbiome in 75 amyloid-positive AD patients and 100 cognitively healthy controls participating in the AlzBiom study.

Transcriptomic Basis of Serum Resistance and Virulence Related Traits in XDR Evolved Under Antibiotic Pressure in a Morbidostat Device.

Colistin is a last resort antibiotic against the critical status pathogen . Virulence and related traits such as biofilm formation and serum resistance after exposure to sub-inhibitory levels of colistin have been underexplored. We cultivated in a semi-automated morbidostat device with colistin, metronidazole and a combination of the two antibiotics for 21 days, and completed RNA-Seq to uncover the transcriptional changes over time.

Tracking of Antibiotic Resistance Transfer and Rapid Plasmid Evolution in a Hospital Setting by Nanopore Sequencing.

Infections with multidrug-resistant bacteria often leave limited or no treatment options. The transfer of antimicrobial resistance genes (ARG) carrying plasmids between bacterial species by horizontal gene transfer represents an important mode of expansion of ARGs. Here, we demonstrate the application of Nanopore sequencing in a hospital setting for monitoring transfer and rapid evolution of antibiotic resistance plasmids within and across multiple species.

Description of sp. nov., isolated from human rectal swabs and stool samples.

Nine independent Gram-negative bacterial strains were isolated from rectal swabs or stool samples of immunocompromised patients from two different wards of a university hospital. All isolates were phylogenetically analysed based on their 16S rRNA gene sequence, housekeeping gene , multilocus sequence analysis of concatenated partial , , and sequences, and by whole genome sequencing data. The analysed strains of the new species cluster together and form a separate branch with NBRC105721 as the most closely related species.

Identification of Drug Resistance Determinants in a Clinical Isolate of Pseudomonas aeruginosa by High-Density Transposon Mutagenesis.

With the aim to identify potential new targets to restore antimicrobial susceptibility of multidrug-resistant (MDR) isolates, we generated a high-density transposon (Tn) insertion mutant library in an MDR bloodstream isolate (isolate ID40). The depletion of Tn insertion mutants upon exposure to cefepime or meropenem was measured in order to determine the common resistome for these clinically important antipseudomonal β-lactam antibiotics. The approach was validated by clean deletions of genes involved in peptidoglycan synthesis/recycling, such as the genes for the lytic transglycosylase MltG, the murein (Mur) endopeptidase MepM1, the MurNAc/GlcNAc kinase AmgK, and the uncharacterized protein YgfB, all of which were identified in our screen as playing a decisive role in survival after treatment with cefepime or meropenem.

Pathogenicity of Clinical OXA-48 Isolates and Impact of the OXA-48 IncL Plasmid on Virulence and Bacterial Fitness.

OXA-48 is the most common carbapenemase in Enterobacterales in Germany and one of the most frequent carbapenemases worldwide. Several reports have associated with a virulent host phenotype. To challenge this hypothesis, 35 OXA-48-producing clinical isolates of ( = 15) and ( = 20) were studied , employing the infection model and by whole-genome sequencing.

Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study.

Background: The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of individual antibiotics on the human gut microbiome and resistome.

Results: Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics; one cohort was treated with ciprofloxacin in a hospital in Tübingen and the other with cotrimoxazole in a hospital in Cologne.

Oxidative stress drives the selection of quorum sensing mutants in the population.

Quorum sensing (QS) is the central mechanism by which social interactions within the bacterial community control bacterial behavior. QS-negative cells benefit by exploiting public goods produced by the QS-proficient population. Mechanisms to keep the balance between producers and nonproducers within the population are expected but have not been elucidated for peptide-based QS systems in gram-positive pathogens.

Molecular Evolution of Extensively Drug-Resistant (XDR) Strains From Patients and Hospital Environment in a Prolonged Outbreak.

In this study, we aimed to elucidate a prolonged outbreak of extensively drug-resistant (XDR) , at two adjacent hospitals over a time course of 4 years. Since all strains exhibited a similar antibiotic susceptibility pattern and carried the carbapenemase gene bla, a monoclonal outbreak was assumed. To shed light on the intra-hospital evolution of these strains over time, whole genome sequence (WGS) analysis of 100 clinical and environmental outbreak strains was employed.

Expansion of Vancomycin-Resistant in an Academic Tertiary Hospital in Southwest Germany: a Large-Scale Whole-Genome-Based Outbreak Investigation.

Vancomycin-resistant (VREfm) is a frequent cause of nosocomial outbreaks. In the second half of 2015, a sharp increase in the incidence of VREfm was observed at our university medical center. Next-generation sequencing (NGS) was used to analyze the first isolates of VREfm recovered from patients between 2010 and 2016 ( = 773) in order to decipher epidemiological change, outbreak dynamics, and possible transmission routes.

Draft Genome Sequence of the Extensively Drug-Resistant Pseudomonas aeruginosa Clinical Isolate TUEPA7472.

Pseudomonas aeruginosa TUEPA7472 is extensively drug resistant (XDR) and is a representative Gram-negative rod that is multiresistant toward 4 classes of clinically relevant antibiotics (4MRGN). The 6.8-Mb draft genome sequence of this strain provides insight into these resistance mechanisms and the potential of the strain to produce virulence factors.

Colistin susceptibility test evaluation of multiple-resistance-level Pseudomonas aeruginosa isolates generated in a morbidostat device.

Objectives: Colistin is a last-resort antibiotic against the critical-status pathogen Pseudomonas aeruginosa. There is still uncertainty regarding how to accurately measure colistin susceptibility in P. aeruginosa.

Long-Term, Low-Frequency Cluster of a German-Imipenemase-1-Producing Enterobacter hormaechei ssp. steigerwaltii ST89 in a Tertiary Care Hospital in Germany.

Enterobacter cloacae complex is a common cause of hospital outbreaks. A retrospective and prospective molecular analysis of carbapenem-resistant clinical isolates in a tertiary care center demonstrated an outbreak of a German-imipenemase-1 (GIM-1) metallo-beta-lactamase-producing Enterobacter hormaechei ssp. steigerwaltii affecting 23 patients between 2009 and 2016.

Genomic characterisation of clinical and environmental Pseudomonas putida group strains and determination of their role in the transfer of antimicrobial resistance genes to Pseudomonas aeruginosa.

Background: Pseudomonas putida is a Gram-negative, non-fermenting bacterium frequently encountered in various environmental niches. P. putida rarely causes disease in humans, though serious infections and outbreaks have been reported from time to time.

Cholesterol and host cell surface proteins contribute to cell-cell fusion induced by the Burkholderia type VI secretion system 5.

Following escape into the cytoplasm of host cells, Burkholderia pseudomallei and the related species Burkholderia thailandensis employ the type VI secretion system 5 (T6SS-5) to induce plasma membrane fusion with an adjacent host cell. This process leads to the formation of multinucleated giant cells and facilitates bacterial access to an uninfected host cell in a direct manner. Despite its importance in virulence, the mechanism of the T6SS-5 and the role of host cell factors in cell-cell fusion remain elusive.

Rapid and Consistent Evolution of Colistin Resistance in Extensively Drug-Resistant Pseudomonas aeruginosa during Morbidostat Culture.

Colistin is a last-resort antibiotic commonly used against multidrug-resistant strains of To investigate the potential for evolution of resistance against colistin and to map the molecular targets of colistin resistance, we exposed two isolates to colistin using a continuous-culture device known as a morbidostat. As a result, colistin resistance reproducibly increased 10-fold within 10 days and 100-fold within 20 days, along with highly stereotypic yet strain-specific mutation patterns. The majority of mutations hit the two-component signaling system and genes involved in lipopolysaccharide (LPS) synthesis, including , , and We tracked the frequencies of all arising mutations by whole-genome deep sequencing every 3 to 4 days to obtain a detailed picture of the dynamics of resistance evolution, including competition and displacement among multiple resistant subpopulations.

Evaluation of the Accelerate Pheno System for Fast Identification and Antimicrobial Susceptibility Testing from Positive Blood Cultures in Bloodstream Infections Caused by Gram-Negative Pathogens.

Bloodstream infections (BSI) are an important cause of morbidity and mortality. Increasing rates of antimicrobial-resistant pathogens limit treatment options, prompting an empirical use of broad-range antibiotics. Fast and reliable diagnostic tools are needed to provide adequate therapy in a timely manner and to enable a de-escalation of treatment.

A simple statistical test of taxonomic or functional homogeneity using replicated microbiome sequencing samples.

One important question in microbiome analysis is how to assess the homogeneity of the microbial composition in a given environment, with respect to a given analysis method. Do different microbial samples taken from the same environment follow the same taxonomic distribution of organisms, or the same distribution of functions? Here we provide a non-parametric statistical "triangulation test" to address this type of question. The test requires that multiple replicates are available for each of the biological samples, and it is based on three-way computational comparisons of samples.

Protracted Regional Dissemination of GIM-1-Producing Serratia marcescens in Western Germany.

The metallo-beta-lactamase GIM-1 has been found in various bacterial host species nearly exclusively in western Germany. However, not much is known about the epidemiology of GIM-1-positive Here we report on a surprisingly protracted regional dissemination. In-hospital transmission was investigated by using conventional epidemiological tools to identify spatiotemporal links.

Susceptibility to cephalosporin combinations and aztreonam/avibactam among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission.

As part of the multicentre Antibiotic Therapy Optimisation Study (ATHOS), minimum inhibitory concentrations (MICs) were determined for cephalosporins alone and in combination with the β-lactamase inhibitors tazobactam, clavulanic acid and avibactam against third-generation cephalosporin-resistant Escherichia coli, Klebsiella spp. and Enterobacter spp. isolates collected in German hospitals.

Susceptibility to penicillin derivatives among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission.

As part of the multicenter Antibiotic Therapy Optimisation Study-the largest study on the prevalence of third-generation cephalosporin-resistant Enterobacteriaceae carriage upon hospital admission-minimum inhibitory concentration values were generated for ampicillin/sulbactam, amoxicillin/clavulanic acid, piperacillin/tazobactam, mecillinam, mecillinam/clavulanic acid, and temocillin against third-generation cephalosporin-resistant Escherichia coli, Klebsiella species and Enterobacter species.

Translational metagenomics and the human resistome: confronting the menace of the new millennium.

The increasing threat of antimicrobial resistance poses one of the greatest challenges to modern medicine. The collection of all antimicrobial resistance genes carried by various microorganisms in the human body is called the human resistome and represents the source of resistance in pathogens that can eventually cause life-threatening and untreatable infections. A deep understanding of the human resistome and its multilateral interaction with various environments is necessary for developing proper measures that can efficiently reduce the spread of resistance.