scholarly journals Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Bernadette C. Young ◽  
Chieh-Hsi Wu ◽  
Jane Charlesworth ◽  
Sarah Earle ◽  
James R. Price ◽  
...  

Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Vo Phuoc Tuan ◽  
Koji Yahara ◽  
Ho Dang Quy Dung ◽  
Tran Thanh Binh ◽  
Pham Huu Tung ◽  
...  

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.


2021 ◽  
Author(s):  
Bernadette C Young ◽  
Chieh-Hsi Wu ◽  
Jane Charlesworth ◽  
Sarah Earle ◽  
James R Price ◽  
...  

AbstractBackgroundStaphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease.MethodsTo investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage.ResultsAll major global lineages were represented in both bacteraemia and carriage, with no evidence for different attack rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (p=10−8.9-10−9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10−5.3) as well as the presence of SCCmec (HMP=10−4.4).Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (p=10−7.1-10−19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (p=10−7.2).ConclusionsIn an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment.Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and hospital-associated carriage, suggesting that AMR increases the propensity not only to survive in hospital environments, but also to cause invasive disease.


Author(s):  
Dominic A. Stoll ◽  
Nicolas Danylec ◽  
Christina Grimmler ◽  
Sabine E. Kulling ◽  
Melanie Huch

The strain Adlercreutzia caecicola DSM 22242T (=CCUG 57646T=NR06T) was taxonomically described in 2013 and named as Parvibacter caecicola Clavel et al. 2013. In 2018, the name of the strain DSM 22242T was changed to Adlercreutzia caecicola (Clavel et al. 2013) Nouioui et al. 2018 due to taxonomic investigations of the closely related genera Adlercreutzia, Asaccharobacter and Enterorhabdus within the phylum Actinobacteria . However, the first whole draft genome of strain DSM 22242T was published by our group in 2019. Therefore, the genome was not available within the study of Nouioui et al. (2018). The results of the polyphasic approach within this study, including phenotypic and biochemical analyses and genome-based taxonomic investigations [genome-wide average nucleotide identity (gANI), alignment fraction (AF), average amino acid identity (AAI), percentage of orthologous conserved proteins (POCP) and genome blast distance phylogeny (GBDP) tree], indicated that the proposed change of the name Parvibacter caecicola to Adlercreutzia caecicola was not correct. Therefore, it is proposed that the correct name of Adlercreutzia caecicola (Clavel et al. 2013) Nouioui et al. 2018 strain DSM 22242T is Parvibacter caecicola Clavel et al. 2013.


Author(s):  
Jiao Huang ◽  
Ying Huang

A novel filamentous Actinobacterium, designated strain FXJ1.1311T, was isolated from soil collected in Ngari (Ali) Prefecture, Qinghai-Tibet Plateau, western PR China. The strain showed antimicrobial activity against Gram-positive bacteria and Fusarium oxysporum. Results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain FXJ1.1311T belonged to the genus Lentzea and showed the highest sequence similarity to Lentzea guizhouensis DHS C013T (98.04%). Morphological and chemotaxonomic characteristics supported its assignment to the genus Lentzea . The genome-wide average nucleotide identity between strain FXJ1.1311T and L. guizhouensis DHS C013T as well as other Lentzea type strains was <82.2 %. Strain FXJ1.1311T also formed a monophyletic line distinct from the known Lentzea species in the phylogenomic tree. In addition, physiological and chemotaxonomic characteristics allowed phenotypic differentiation of the novel strain from L. guizhouensis . Based on the evidence presented here, strain FXJ1.1311T represents a novel species of the genus Lentzea , for which the name Lentzea tibetensis sp. nov. is proposed. The type strain is FXJ1.1311T (=CGMCC 4.7383T=DSM 104975T).


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Iain R. Timmins ◽  
Francesco Zaccardi ◽  
Christopher P. Nelson ◽  
Paul W. Franks ◽  
Thomas Yates ◽  
...  

A Correction to this paper has been published: 10.1038/s42003-020-01447-6.


Author(s):  
Eric A. Smith ◽  
Kirk E. Anderson ◽  
Vanessa Corby-Harris ◽  
Quinn S. McFrederick ◽  
Audrey J. Parish ◽  
...  

Honey bees are important pollinators of many major crops and add billions of dollars annually to the US economy through their services. Recent declines in the health of the honey bee have startled researchers and lay people alike as honey bees are agriculture’s most important pollinator. One factor that may influence colony health is the microbial community. Although honey bee worker guts have a characteristic community of bee-specific microbes, the honey bee queen digestive tracts are colonized predominantly by a single acetic acid bacterium tentatively named ‘Parasaccharibacter apium’. This bacterium is related to flower-associated microbes such as Saccharibacter floricola , and initial phylogenetic analyses placed it as sister to these environmental bacteria. We used a combination of phylogenetic and sequence identity methods to better resolve evolutionary relationships among ‘P. apium’, strains in the genus Saccharibacter , and strains in the closely related genus Bombella . Interestingly, measures of genome-wide average nucleotide identity and aligned fraction, coupled with phylogenetic placement, indicate that many strains labelled as ‘P. apium’ and Saccharibacter species are all the same species as Bombella apis . We propose reclassifying these strains as Bombella apis and outline the data supporting that classification below.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3618 ◽  
Author(s):  
Rana Dajani ◽  
Jin Li ◽  
Zhi Wei ◽  
Michael E. March ◽  
Qianghua Xia ◽  
...  

The prevalence of Type II Diabetes (T2D) has been increasing and has become a disease of significant public health burden in Jordan. None of the previous genome-wide association studies (GWAS) have specifically investigated the Middle East populations. The Circassian and Chechen communities in Jordan represent unique populations that are genetically distinct from the Arab population and other populations in the Caucasus. Prevalence of T2D is very high in both the Circassian and Chechen communities in Jordan despite low obesity prevalence. We conducted GWAS on T2D in these two populations and further performed meta-analysis of the results. We identified a novel T2D locus at chr20p12.2 at genome-wide significance (rs6134031, P = 1.12 × 10−8) and we replicated the results in the Wellcome Trust Case Control Consortium (WTCCC) dataset. Another locus at chr12q24.31 is associated with T2D at suggestive significance level (top SNP rs4758690, P = 4.20 × 10−5) and it is a robust eQTL for the gene, MLXIP (P = 1.10 × 10−14), and is significantly associated with methylation level in MLXIP, the functions of which involves cellular glucose response. Therefore, in this first GWAS of T2D in Jordan subpopulations, we identified novel and unique susceptibility loci which may help inform the genetic underpinnings of T2D in other populations.


2019 ◽  
Author(s):  
Yanhong Lou ◽  
Yun Chen ◽  
Zhihao Liu ◽  
Mingjie Sun ◽  
Fei Han ◽  
...  

Abstract Background: Foxtail millet [Setaria italica (L.) P. Beauv.] is a particularly important cereal and fodder crop in arid and semi-arid regions. The genomic variation and alleles underpinning agronomic and quality traits are important for foxtail millet improvement. To better understand the diversity of foxtail millet and facilitate the genetic dissection of its agronomic and quality traits, we used high-quality single nucleotide polymorphisms (SNPs) to perform a genome-wide association study (GWAS). Results: Using genotyping-by-sequencing, 107 foxtail millet accessions were sequenced, and further analysis revealed 72,181 high-quality SNPs, of which 53 were significantly associated with 15 agronomic and quality traits. These SNPs were distributed across the nine chromosomes of foxtail millet; 44 were located in intergenic regions, whereas one and eight SNPs were located in exon and intron regions, respectively. The GWAS revealed that 28 SNPs were associated with a single trait. Conclusions: For some of the significant SNPs, favourable genotypes showed pyramiding effects for several traits. The 53 loci identified in this study will therefore be useful for breeding programs aimed at foxtail millet improvement.


2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Adrian Sven Geissler ◽  
Christian Anthon ◽  
Ferhat Alkan ◽  
Enrique González-Tortuero ◽  
Line Dahl Poulsen ◽  
...  

A large part of our current understanding of gene regulation in Gram-positive bacteria is based on Bacillus subtilis , as it is one of the most well studied bacterial model systems. The rapid growth in data concerning its molecular and genomic biology is distributed across multiple annotation resources. Consequently, the interpretation of data from further B. subtilis experiments becomes increasingly challenging in both low- and large-scale analyses. Additionally, B. subtilis annotation of structured RNA and non-coding RNA (ncRNA), as well as the operon structure, is still lagging behind the annotation of the coding sequences. To address these challenges, we created the B. subtilis genome atlas, BSGatlas, which integrates and unifies multiple existing annotation resources. Compared to any of the individual resources, the BSGatlas contains twice as many ncRNAs, while improving the positional annotation for 70 % of the ncRNAs. Furthermore, we combined known transcription start and termination sites with lists of known co-transcribed gene sets to create a comprehensive transcript map. The combination with transcription start/termination site annotations resulted in 717 new sets of co-transcribed genes and 5335 untranslated regions (UTRs). In comparison to existing resources, the number of 5′ and 3′ UTRs increased nearly fivefold, and the number of internal UTRs doubled. The transcript map is organized in 2266 operons, which provides transcriptional annotation for 92 % of all genes in the genome compared to the at most 82 % by previous resources. We predicted an off-target-aware genome-wide library of CRISPR–Cas9 guide RNAs, which we also linked to polycistronic operons. We provide the BSGatlas in multiple forms: as a website (https://rth.dk/resources/bsgatlas/), an annotation hub for display in the UCSC genome browser, supplementary tables and standardized GFF3 format, which can be used in large scale -omics studies. By complementing existing resources, the BSGatlas supports analyses of the B. subtilis genome and its molecular biology with respect to not only non-coding genes but also genome-wide transcriptional relationships of all genes.


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