scholarly journals Enterococcus faeciumgenome dynamics during long-term asymptomatic patient gut colonization

2019 ◽  
Author(s):  
Jumamurat R. Bayjanov ◽  
Jery Baan ◽  
Malbert R.C. Rogers ◽  
Annet Troelstra ◽  
Rob J.L. Willems ◽  
...  
Keyword(s):  
Insertion Sequence ◽  
Evolutionary Rate ◽  
Multidrug Resistant ◽  
Gene Gain ◽  
Nucleotide Polymorphisms ◽  
Single Patient ◽  
Nosocomial Pathogen ◽  
Single Nucleotide ◽  
Gut Colonization

AbstractBackgroundE. faeciumis 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-resistantE. faeciumstrains 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 toE. faeciumclade 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 ISEfa5showing a unique pattern of location in 24 of the 25 isolates, suggesting widespread ISEfa5excision and insertion into the genome during gut colonization.ConclusionsOur findings show that theE. faeciumgenome 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.

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

2019 ◽  
Vol 5 (7) ◽  
Author(s):  
Jumamurat R. Bayjanov ◽  
Jery Baan ◽  
Malbert R. C. Rogers ◽  
Annet Troelstra ◽  
Rob J. L. Willems ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Type Species ◽  
Multidrug Resistant ◽  
Gene Gain ◽  
Nucleotide Polymorphisms ◽  
Nosocomial Pathogen ◽  
Content Type ◽  
Link Type ◽  
Gut Colonization ◽  
Genome Dynamics

Enterococcus 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 of describing the genome dynamics of this species. The 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 consisted entirely 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 hospitalization. We estimated the evolutionary rate of two clonal groups that each colonized single patients 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 12 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. Our findings show that the E. faecium genome is highly dynamic during asymptomatic colonization of the human gut. We observed 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.

scholarly journals Functional Inflammatory Genotypes in Ischemic Stroke: Could We Use Them to Predict Age of Onset and Long-Term Outcome?

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stella Marousi ◽  
Anna Antonacopoulou ◽  
Haralambos Kalofonos ◽  
Panagiotis Papathanasopoulos ◽  
Marina Karakantza ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cox Regression ◽  
Age Of Onset ◽  
Adverse Outcome ◽  
Nucleotide Polymorphisms ◽  
Term Outcome ◽  
Single Nucleotide ◽  
Long Term Outcome ◽  
Tnf Α

Functional single-nucleotide polymorphisms (SNPs) of inflammatory cytokines have been previously related to the occurrence of an ischemic stroke (IS). We investigated whether five functional SNPs (i.e., TNF-α-308G>A, IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A) might be associated with the age of onset and 6-month outcome of an acute IS. A probe-free real-time PCR methodology was used to genotype 145 consecutively admitted cases with a first-ever IS. Simple Kaplan-Mayer and adjusted Cox regression analyses showed no association between inflammatory genotypes and the age of IS onset. IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A were not found to significantly contribute to the long-term outcome of the disease. However, carriage of the TNF-α-308 GG genotype was significantly associated with reduced odds for an adverse outcome. Larger studies are needed to confirm our results.

scholarly journals LB1. Regional Assessment and Containment of Candida auris Transmission in Post-Acute Care Settings—Orange County, California, 2019

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S993-S993 ◽  
Author(s):  
Ellora Karmarkar ◽  
Ellora Karmarkar ◽  
Kathleen O’Donnell ◽  
Christopher Prestel ◽  
Kaitlin Forsberg ◽  
...  
Keyword(s):  
Acute Care ◽  
Orange County ◽  
Invasive Disease ◽  
Nucleotide Polymorphisms ◽  
Nursing Facilities ◽  
Candida Auris ◽  
Single Nucleotide ◽  
Skilled Nursing ◽  
And Control

Abstract Background Patients in long-term acute care hospitals (LTACHs) and skilled nursing facilities with ventilator units (VSNFs) are at high risk for Candida auris colonization; among patients colonized with this emerging pathogen, 5%–10% develop invasive disease with >45% mortality. In September 2018, a California LTACH-affiliated laboratory began enhanced C. auris surveillance by classifying species of Candida isolated from routine urine specimens. In February 2019, the first known Southern California case was detected in an Orange County (OC) LTACH; the patient had not traveled outside the region, indicating local acquisition. We performed point prevalence surveys (PPS) and infection prevention (IP) assessments at all OC LTACHs and VSNF subacute units to identify patients colonized with C. auris and control transmission. Methods During March–August 2019, we conducted PPS at facilities by collecting composite axilla and groin swabs for C. auris polymerase chain reaction testing and reflex culture from all patients who assented. Facilities with ≥1 C. auris-colonized patient repeated a PPS every 2 weeks to assess for new transmission. Isolate relatedness was assessed by whole-genome sequencing (WGS). We evaluated hand hygiene (HH) adherence, access to alcohol-based hand rubs (ABHR), and cleaning of high-touch surfaces to guide IP recommendations. Results The first PPS at all OC LTACHs (n = 3) and adult VSNFs (n = 14) identified 45 C. auris-colonized patients in 3 (100%) LTACHs and 6 (43%) VSNFs; after repeated PPS, the total count reached 124. Most patients (70%) were at 2 facilities (Table 1). Three of 124 patients developed candidemia. To date, isolates from 48 patients have completed WGS; all were highly related (<11 single-nucleotide polymorphisms) in the African clade. Of 9 facilities with C. auris, 5 had HH adherence < 50%, 3 had limited ABHR, and at 2, <60% of assessed high-touch surfaces were clean. We recommended regular HH and cleaning audits, and increased ABHR. Conclusion Our investigation, prompted by enhanced surveillance, identified C. auris at 9 OC facilities. WGS indicated a single introduction and local transmission. Early detection, followed by rapid county-wide investigation and IP support, enabled containment efforts for C. auris in OC. Disclosures All authors: No reported disclosures.

scholarly journals Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations with Severity of TB

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1487
Author(s):  
Michael L. McHenry ◽  
Eddie M. Wampande ◽  
Moses L. Joloba ◽  
LaShaunda L. Malone ◽  
Harriet Mayanja-Kizza ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Clinical Presentation ◽  
Sub Saharan Africa ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Genomes ◽  
Genome Wide ◽  
Sub Saharan ◽  
Cellular Replication

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10−8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host–pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human–MTBC coevolution is likely to explain patterns of disease severity.

scholarly journals Dopaminergic genes are associated with both directed and random exploration

2018 ◽  
Author(s):  
Samuel J. Gershman ◽  
Bastian Greshake Tzovaras
Keyword(s):  
Individual Differences ◽  
Single Nucleotide Polymorphisms ◽  
Optimal Solution ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Trade Off ◽  
Effective Strategies ◽  
Dopaminergic Genes ◽  
High Uncertainty

AbstractIn order to maximize long-term rewards, agents must balance exploitation (choosing the option with the highest payoff) and exploration (gathering information about options that might have higher payoffs). Although the optimal solution to this trade-off is intractable, humans make use of two effective strategies: selectively exploring options with high uncertainty (directed exploration), and increasing the randomness of their choices when they are more uncertain (random exploration). Using a task that independently manipulates these two forms of exploration, we show that single nucleotide polymorphisms related to dopamine are associated with individual differences in exploration strategies. Variation in a gene linked to prefrontal dopamine (COMT) predicted the degree of directed exploration, as well as the overall randomness of responding. Variation in a gene linked to striatal dopamine (DARPP-32) predicted the degree of both directed and random exploration. These findings suggest that dopamine makes multiple contributions to exploration, depending on its afferent target.

scholarly journals Intrahost-diversity of influenza A virus in upper and lower respiratory tract derived samples from a college community

2021 ◽  
Author(s):  
Nicolae Sapoval ◽  
P. Jacob Bueno de Mesquita ◽  
Yunxi Liu ◽  
Roger Wang ◽  
Tian Rui Liu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Nucleotide Polymorphisms ◽  
Single Patient ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Site Specific ◽  
College Community

Motivation. Influenza is a rapidly mutating RNA virus responsible for annual epidemics causing substantial morbidity, mortality, and economic loss. Characterizing influenza virus mutational diversity and evolutionary processes within and between human hosts can provide tools to help track and understand transmission events. In this study we investigated possible differences between the intrahost genomic content of influenza virus in upper respiratory swabs and exhaled aerosols thought to be enriched for virus from the lower respiratory tract. Results. We examined the sequences of specimens collected from influenza A virus (IAV) infected college community members from December 2012 through May 2013. We analyzed four types of IAV samples μm aerosols (N=38), coarse >5μm aerosols (N=27), nasopharyngeal (N=53), and oropharyngeal swabs (N=47)) collected from 42 study participants with 60 sampling instances. Eighteen (42.9%) participants had data from four sample types (nasopharyngeal swab, oropharyngeal swab, coarse aerosol, fine aerosol) included in the analysis, 10 (23.8%) had data from 3 sample types, 10 (23.8%) had data from 2 sample types, and 4 (9.5%) had data from one type of sample included in the analysis. We found that 481 (53.3%) consensus single nucleotide polymorphisms are shared by all sample types and 600 (66.5%) are shared by at least three different sample types. We observed that within a single patient consensus and non-consensus single nucleotide variants are shared across all sample types. Finally, we inferred a phylogenetic tree using consensus sequences and found that samples derived from a single patient are monophyletic. Conclusions. Single nucleotide polymorphisms did not differentiate between samples with varying origin along the respiratory tree. We found that signatures of variation in non-consensus intrahost single nucleotide variants are host and sample, but not site-specific. We conclude that the genomic information available does not allow us to discern a transmission route. Future investigation into whether any site-specific mutational signatures emerge over a longer period of infection, for example in immunocompromised hosts, can be interesting from the virus evolution perspective.

scholarly journals Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 90
Author(s):  
Michael Pietsch ◽  
Yvonne Pfeifer ◽  
Stephan Fuchs ◽  
Guido Werner
Keyword(s):  
Escherichia Coli ◽  
Growth Rates ◽  
Beta Lactamase ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genomic Changes ◽  
E Coli ◽  
Fitness Effects ◽  
Growth Differences

(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, we investigated fitness effects after a conjugative transfer of plasmids containing various beta-lactamase genes transferred into Escherichia coli. (2) Methods: Fourteen beta-lactamase-encoding plasmids were transferred from clinical donor strains to E. coli J53. Growth rates were compared for all transconjugants and the recipient. Selected transconjugants were challenged in long-term growth experiments. Growth rates were assessed at different time points during growth for 500 generations. Whole-genome sequencing (WGS) of initial and evolved transconjugants was determined. Results: Most plasmid acquisitions resulted in growth differences, ranging from −4.5% to 7.2%. Transfer of a single blaCMY-16-carrying plasmid resulted in a growth burden and a growth benefit in independent mating. Long-term growth led to a compensation of fitness burdens and benefits. Analyzing WGS revealed genomic changes caused by Single Nucleotide Polymorphisms (SNPs) and insertion sequences over time. Conclusions: Fitness effects associated with plasmid acquisitions were variable. Potential compensatory mutations identified in transconjugants’ genomes after 500 generations give interesting insights into aspects of plasmid–host adaptations.

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