Biology subjects

Bayjanov, J. R.

Publications and source records attributed to Bayjanov, J. R..

5 recordsLinked to original sources

bioRxiv2023

Integrative analysis of CAKUT multi-omics data

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood end-stage renal disease and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. Multi-omics experiments, including amniotic fluid miRNome, peptidome, and proteome analyses, can shed light on foetal kidney development in non-severe CAKUT patients compared to severe CAKUT cases. We performed FAIRification of these omics data sets to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.

systems biology↗

bioRxiv2019

Enterococcus faecium genome dynamics during long-term asymptomatic patient gut colonization

BackgroundE. faecium is a gut commensal of humans and animals. In addition, it has recently emerged as an important nosocomial pathogen through the acquisition of genetic elements that confer resistance to antibiotics and virulence. We performed a whole-genome sequencing based study on 96 multidrug-resistant E. faecium strains that asymptomatically colonized five patients with the aim to describe the genome dynamics of this species. ResultsThe patients were hospitalized on multiple occasions and isolates were collected over periods ranging from 15 months to 6.5 years. Ninety-five of the sequenced isolates belonged to E. faecium clade A1, which was previously determined to be responsible for the vast majority of clinical infections. The clade A1 strains clustered into six clonal groups of highly similar isolates, three of which entirely consisted of isolates from a single patient. We also found evidence of concurrent colonization of patients by multiple distinct lineages and transfer of strains between patients during hospitalisation. We estimated the evolutionary rate of two clonal groups that colonized a single patient at 12.6 and 25.2 single nucleotide polymorphisms (SNPs)/genome/year. A detailed analysis of the accessory genome of one of the clonal groups revealed considerable variation due to gene gain and loss events, including the chromosomal acquisition of a 37 kbp prophage and the loss of an element containing carbohydrate metabolism-related genes. We determined the presence and location of twelve different Insertion Sequence (IS) elements, with ISEfa5 showing a unique pattern of location in 24 of the 25 isolates, suggesting widespread ISEfa5 excision and insertion into the genome during gut colonization. ConclusionsOur findings show that the E. faecium genome is highly dynamic during asymptomatic colonization of the patient gut. We observe considerable genomic flexibility due to frequent horizontal gene transfer and recombination, which can contribute to the generation of genetic diversity within the species and, ultimately, can contribute to its success as a nosocomial pathogen.

microbiology↗

bioRxiv2017

The microbiome and resistome of hospital sewage during passage through the community sewer system

Effluents from wastewater treatment plants (WWTPs) have been proposed to act as point sources of antibiotic-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) in the environment. Hospital sewage may contribute to the spread of ARB and ARGs as it contains the feces and urine of hospitalized patients, who are more frequently colonized with multi-drug resistant bacteria than the general population. However, whether hospital sewage noticeably contributes to the quantity and diversity of ARGs in the general sewerage system has not yet been determined.\n\nHere, we employed culture-independent techniques, namely 16S rRNA and nanolitre-scale quantitative PCRs, to describe the role of hospital effluent as a point source of ARGs in the sewer system, through comparing microbiota composition and levels of ARGs in hospital sewage with WWTP influent, WWTP effluent and the surface water in which the effluent is released.\n\nCompared to other sample sites, hospital sewage was richest in human-associated bacteria and contained the highest relative levels of ARGs. Yet, the abundance of ARGs was comparable in WWTPs with and without hospital wastewater, suggesting that hospitals do not contribute to the spread of ARGs in countries with a functioning sewerage system.

microbiology↗

bioRxiv2017

Gut microbiota and resistome dynamics in intensive care patients receiving selective digestive tract decontamination

BackgroundCritically ill patients hospitalized in an Intensive Care Unit (ICU) are at increased risk of acquiring potentially life-threatening infections with opportunistic pathogens. The gut microbiota of ICU patients forms an important reservoir for these infectious agents. To suppress gut colonization with opportunistic pathogens, a prophylactic antibiotic regimen, termed Selective decontamination of the digestive tract (SDD), may be used. SDD has previously been shown to improve clinical outcome in ICU patients, but the impact of ICU hospitalization and SDD on the gut microbiota remains largely unknown. Here, we characterize the composition of the gut microbiota and its antimicrobial resistance genes ( the resistome) of ICU patients during SDD.\n\nResultsDuring ICU-stay, 30 fecal samples of ten patients were collected. Additionally, feces were collected from five of these patients after transfer to a medium-care ward and cessation of SDD. As a control group, feces from ten healthy subjects were collected twice, with a one-year interval. Gut microbiota and resistome composition were determined using 16S rRNA phylogenetic profiling and nanolitre-scale quantitative PCRs.\n\nThe microbiota of the ICU patients differed from the microbiota of healthy subjects and was characterized by low microbial diversity, decreased levels of E. coli and of anaerobic Gram-positive, butyrate-producing bacteria of the Clostridium clusters IV and XIVa, and an increased abundance of Bacteroidetes and enterococci. Four resistance genes (aac(6')-Ii, ermC, qacA, tetQ), providing resistance to aminoglycosides, macrolides, disinfectants and tetracyclines respectively, were significantly more abundant among ICU patients than in healthy subjects, while a chloramphenicol resistance gene (catA) and a tetracycline resistance gene (tetW) were more abundant in healthy subjects.\n\nConclusionsThe microbiota and resistome of ICU patients and healthy subjects were noticeably different, but importantly, levels of E. coli remained low during ICU hospitalization, presumably due to SDD therapy. Selection for four antibiotic resistance genes was observed, but none of these are of particular concern as they do not contribute to clinically relevant resistance. Our data support the ecological safety of SDD, at least in settings with low levels of circulating antibiotic resistance.

microbiology↗

bioRxiv2017

Fitness determinants of vancomycin-resistant Enterococcus faecium during growth in human serum

Enterococcus faecium is a commensal of the human gastrointestinal tract and a frequent cause of bloodstream infections in hospitalized patients. Here, we identify genes that contribute to growth of E. faecium in human serum. We first sequenced the genome of E. faecium E745, a vancomycin-resistant clinical isolate, to completion and then compared its transcriptome during exponential growth in rich medium and in human serum by RNA-seq. This analysis revealed that 27.8% of genes on the E. faecium E745 genome were differentially expressed in these two conditions. A gene cluster with a role in purine biosynthesis was among the most upregulated genes in E. faecium E745 upon growth in serum. A high-throughput transposon sequencing (Tn-seq) approach was used to identify conditionally essential genes in E. faecium E745 during growth in serum. Genes involved in de novo nucleotide biosysnthesis (including pyrK_2, pyrF, purD, purH) and a gene encoding a phosphotransferase system subunit (manY_2) were thus identified to be contributing to E. faecium growth in human serum. Transposon mutants in pyrK_2, pyrF, purD, purH and manY_2 were isolated from the library and their impaired growth in human serum was confirmed. In addition, the pyrK_2 and manY_2 mutants also exhibited significantly attenuated virulence in an intravenous zebrafish infection model. We conclude that genes involved in carbohydrate and nucleotide metabolism of E. faecium are essential for growth in human serum and contribute to the pathogenesis of this organism.

microbiology↗