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Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study

Eyre, David W ; Lumley, Sheila F ; O'Donnell, Denise ; [et al.]

eLife Sciences Publications, Ltd ; 2020

In: eLife Vol. 9 ( 2020-08-21)

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In: eLife, eLife Sciences Publications, Ltd, Vol. 9 ( 2020-08-21)

Abstract: We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45–6.72] ). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99–3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07–2.16] ) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28–0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25–2.21] ) and Asian (1.51 [1.28–1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34–3.15] ).

Type of Medium: Online Resource

ISSN: 2050-084X

URL: Article

DOI: 10.7554/eLife.60675

Language: English

Publisher: eLife Sciences Publications, Ltd

Publication Date: 2020

detail.hit.zdb_id: 2687154-3

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Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus

Everitt, Richard G. ; Didelot, Xavier ; Batty, Elizabeth M. ; [et al.]

Springer Science and Business Media LLC ; 2014

In: Nature Communications Vol. 5, No. 1 ( 2014-05-23)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2014-05-23)

Abstract: Horizontal gene transfer is an important driver of bacterial evolution, but genetic exchange in the core genome of clonal species, including the major pathogen Staphylococcus aureus , is incompletely understood. Here we reveal widespread homologous recombination in S. aureus at the species level, in contrast to its near-complete absence between closely related strains. We discover a patchwork of hotspots and coldspots at fine scales falling against a backdrop of broad-scale trends in rate variation. Over megabases, homoplasy rates fluctuate 1.9-fold, peaking towards the origin-of-replication. Over kilobases, we find core recombination hotspots of up to 2.5-fold enrichment situated near fault lines in the genome associated with mobile elements. The strongest hotspots include regions flanking conjugative transposon ICE 6013 , the staphylococcal cassette chromosome (SCC) and genomic island νSaα. Mobile element-driven core genome transfer represents an opportunity for adaptation and challenges our understanding of the recombination landscape in predominantly clonal pathogens, with important implications for genotype–phenotype mapping.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/ncomms4956

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2014

detail.hit.zdb_id: 2553671-0

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Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease

Young, Bernadette C. ; Golubchik, Tanya ; Batty, Elizabeth M. ; [et al.]

Proceedings of the National Academy of Sciences ; 2012

In: Proceedings of the National Academy of Sciences Vol. 109, No. 12 ( 2012-03-20), p. 4550-4555

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In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 12 ( 2012-03-20), p. 4550-4555

Abstract: Whole-genome sequencing offers new insights into the evolution of bacterial pathogens and the etiology of bacterial disease. Staphylococcus aureus is a major cause of bacteria-associated mortality and invasive disease and is carried asymptomatically by 27% of adults. Eighty percent of bacteremias match the carried strain. However, the role of evolutionary change in the pathogen during the progression from carriage to disease is incompletely understood. Here we use high-throughput genome sequencing to discover the genetic changes that accompany the transition from nasal carriage to fatal bloodstream infection in an individual colonized with methicillin-sensitive S. aureus . We found a single, cohesive population exhibiting a repertoire of 30 single-nucleotide polymorphisms and four insertion/deletion variants. Mutations accumulated at a steady rate over a 13-mo period, except for a cluster of mutations preceding the transition to disease. Although bloodstream bacteria differed by just eight mutations from the original nasally carried bacteria, half of those mutations caused truncation of proteins, including a premature stop codon in an AraC -family transcriptional regulator that has been implicated in pathogenicity. Comparison with evolution in two asymptomatic carriers supported the conclusion that clusters of protein-truncating mutations are highly unusual. Our results demonstrate that bacterial diversity in vivo is limited but nonetheless detectable by whole-genome sequencing, enabling the study of evolutionary dynamics within the host. Regulatory or structural changes that occur during carriage may be functionally important for pathogenesis; therefore identifying those changes is a crucial step in understanding the biological causes of invasive bacterial disease.

Type of Medium: Online Resource

ISSN: 0027-8424 , 1091-6490

URL: Article

DOI: 10.1073/pnas.1113219109

RVK:

TA 1000

RVK:

WA 15000

Language: English

Publisher: Proceedings of the National Academy of Sciences

Publication Date: 2012

detail.hit.zdb_id: 209104-5

detail.hit.zdb_id: 1461794-8

SSG: 11

SSG: 12

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Young, Bernadette C ; Wu, Chieh-Hsi ; Gordon, N Claire ; [et al.]

eLife Sciences Publications, Ltd ; 2017

In: eLife Vol. 6 ( 2017-12-19)

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In: eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-12-19)

Abstract: Bacteria responsible for the greatest global mortality colonize the human microbiota far more frequently than they cause severe infections. Whether mutation and selection among commensal bacteria are associated with infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose colonization. We report that 72% of infections emerged from the nose, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold adaptive enrichments of protein-altering variants in genes responding to rsp, which regulates surface antigens and toxin production; agr, which regulates quorum-sensing, toxin production and abscess formation; and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting infection-associated, short-term, within-host selection pressures. Our results show that signatures of spontaneous adaptive evolution are specifically associated with infection, raising new possibilities for diagnosis and treatment.

Type of Medium: Online Resource

ISSN: 2050-084X

URL: Article

DOI: 10.7554/eLife.30637

DOI: 10.7554/eLife.30637.001

DOI: 10.7554/eLife.30637.002

DOI: 10.7554/eLife.30637.003

DOI: 10.7554/eLife.30637.004

DOI: 10.7554/eLife.30637.005

DOI: 10.7554/eLife.30637.006

DOI: 10.7554/eLife.30637.007

DOI: 10.7554/eLife.30637.008

DOI: 10.7554/eLife.30637.009

DOI: 10.7554/eLife.30637.010

DOI: 10.7554/eLife.30637.011

DOI: 10.7554/eLife.30637.012

DOI: 10.7554/eLife.30637.013

DOI: 10.7554/eLife.30637.014

DOI: 10.7554/eLife.30637.015

DOI: 10.7554/eLife.30637.016

DOI: 10.7554/eLife.30637.017

DOI: 10.7554/eLife.30637.018

DOI: 10.7554/eLife.30637.019

DOI: 10.7554/eLife.30637.065

DOI: 10.7554/eLife.30637.066

Language: English

Publisher: eLife Sciences Publications, Ltd

Publication Date: 2017

detail.hit.zdb_id: 2687154-3

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Evolutionary Trade-Offs Underlie the Multi-faceted Virulence of Staphylococcus aureus

Laabei, Maisem ; Uhlemann, Anne-Catrin ; Lowy, Franklin D. ; [et al.]

Public Library of Science (PLoS) ; 2015

In: PLOS Biology Vol. 13, No. 9 ( 2015-9-2), p. e1002229-

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In: PLOS Biology, Public Library of Science (PLoS), Vol. 13, No. 9 ( 2015-9-2), p. e1002229-

Type of Medium: Online Resource

ISSN: 1545-7885

URL: Article

DOI: 10.1371/journal.pbio.1002229

DOI: 10.1371/journal.pbio.1002229.g001

DOI: 10.1371/journal.pbio.1002229.g002

DOI: 10.1371/journal.pbio.1002229.g003

DOI: 10.1371/journal.pbio.1002229.g004

DOI: 10.1371/journal.pbio.1002229.g005

DOI: 10.1371/journal.pbio.1002229.g006

DOI: 10.1371/journal.pbio.1002229.s001

DOI: 10.1371/journal.pbio.1002229.s002

DOI: 10.1371/journal.pbio.1002229.s003

DOI: 10.1371/journal.pbio.1002229.s004

DOI: 10.1371/journal.pbio.1002229.s005

DOI: 10.1371/journal.pbio.1002229.s006

DOI: 10.1371/journal.pbio.1002229.s007

DOI: 10.1371/journal.pbio.1002229.s008

DOI: 10.1371/journal.pbio.1002229.s009

DOI: 10.1371/journal.pbio.1002229.s010

DOI: 10.1371/journal.pbio.1002229.s011

DOI: 10.1371/journal.pbio.1002229.s012

DOI: 10.1371/journal.pbio.1002229.s013

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2015

detail.hit.zdb_id: 2126773-X

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Within-Host Evolution of Staphylococcus aureus during Asymptomatic Carriage

Golubchik, Tanya ; Batty, Elizabeth M. ; Miller, Ruth R. ; [et al.]

Public Library of Science (PLoS) ; 2013

In: PLoS ONE Vol. 8, No. 5 ( 2013-5-1), p. e61319-

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In: PLoS ONE, Public Library of Science (PLoS), Vol. 8, No. 5 ( 2013-5-1), p. e61319-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0061319

DOI: 10.1371/journal.pone.0061319.g001

DOI: 10.1371/journal.pone.0061319.g002

DOI: 10.1371/journal.pone.0061319.g003

DOI: 10.1371/journal.pone.0061319.g004

DOI: 10.1371/journal.pone.0061319.g005

DOI: 10.1371/journal.pone.0061319.g006

DOI: 10.1371/journal.pone.0061319.t001

DOI: 10.1371/journal.pone.0061319.t002

DOI: 10.1371/journal.pone.0061319.t003

DOI: 10.1371/journal.pone.0061319.s001

DOI: 10.1371/journal.pone.0061319.s002

DOI: 10.1371/journal.pone.0061319.s003

DOI: 10.1371/journal.pone.0061319.s004

DOI: 10.1371/journal.pone.0061319.s005

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2013

detail.hit.zdb_id: 2267670-3

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Daily testing for contacts of individuals with SARS-CoV-2 infection and attendance and SARS-CoV-2 transmission in English secondary schools and colleges: an open-label, cluster-randomised trial

Young, Bernadette C ; Eyre, David W ; Kendrick, Saroj ; [et al.]

Elsevier BV ; 2021

In: The Lancet Vol. 398, No. 10307 ( 2021-10), p. 1217-1229

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In: The Lancet, Elsevier BV, Vol. 398, No. 10307 ( 2021-10), p. 1217-1229

Type of Medium: Online Resource

ISSN: 0140-6736

URL: Article

DOI: 10.1016/S0140-6736(21)01908-5

RVK:

XA 10000

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2067452-1

detail.hit.zdb_id: 3306-6

detail.hit.zdb_id: 1476593-7

SSG: 5,21

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Cigarette smoke exposure redirects Staphylococcus aureus to a virulence profile associated with persistent infection

Lacoma, Alicia ; Edwards, Andrew M. ; Young, Bernadette C. ; [et al.]

Springer Science and Business Media LLC ; 2019

In: Scientific Reports Vol. 9, No. 1 ( 2019-07-25)

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In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-07-25)

Abstract: Tobacco smoking represents the leading preventable cause of death worldwide. Smoking is a recognised risk factor for several pathologies and is detrimental to host immune surveillance and defence. However, the impact of smoking on microbial residents of the nasopharyngeal cavity, in contact with cigarette smoke (CS), is lacking. Staphylococcus aureus is a major human pathogen that colonises the human nasopharynx and causes a wide range of infections. We investigated the impact of CS on specific virulence phenotypes important in S aureus pathogenesis. We observed strain-dependent differences following exposure to CS, namely growth inhibition, augmented biofilm formation, increased invasion of, and persistence within, bronchial alveolar epithelial cells. Additionally, we confirm the critical role of a functional accessory gene regulator (Agr) system in mediating increased biofilm development and host cell invasion and persistence following CS exposure. Furthermore, CS exposure resulted in reduced toxin production. Importantly, exposure of S aureus to CS accelerated the frequency of mutations and resulted in a significant increase in gentamicin-resistant small colony variant (SCV) formation. Mutational analysis revealed that CS induced SCVs emerge via the SOS response DNA mutagenic repair system. Taken together, our results suggest that CS redirects certain S aureus strains to a virulence profile associated with persistence.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-019-47258-6

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2615211-3

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Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis

Young, Bernadette C ; Bush, Stephen J ; Lipworth, Sam ; [et al.]

Oxford University Press (OUP) ; 2022

In: Open Forum Infectious Diseases Vol. 9, No. 9 ( 2022-09-02)

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In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 9 ( 2022-09-02)

Abstract: Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts.

Type of Medium: Online Resource

ISSN: 2328-8957

URL: Article

DOI: 10.1093/ofid/ofac428

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2757767-3

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Fidaxomicin Versus Vancomycin for Clostridium difficile Infection: Meta-analysis of Pivotal Randomized Controlled Trials

Crook, Derrick W. ; Walker, A. Sarah ; Kean, Yin ; [et al.]

Oxford University Press (OUP) ; 2012

In: Clinical Infectious Diseases Vol. 55, No. suppl_2 ( 2012-08-01), p. S93-S103

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 55, No. suppl_2 ( 2012-08-01), p. S93-S103

Type of Medium: Online Resource

ISSN: 1537-6591 , 1058-4838

URL: Article

DOI: 10.1093/cid/cis499

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2012

detail.hit.zdb_id: 2002229-3

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