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dc.contributor.author
Bär, Julian
dc.contributor.author
Boumasmoud, Mathilde
dc.contributor.author
Mairpady Shambat, Srikanth
dc.contributor.author
Vulin, Clément
dc.contributor.author
Huemer, Markus
dc.contributor.author
Schweizer, Tiziano A.
dc.contributor.author
Gómez-Mejia, Alejandro
dc.contributor.author
Eberhard, Nadia
dc.contributor.author
Achermann, Yvonne
dc.contributor.author
Zingg, Patrick O.
dc.contributor.author
Mestres, Carlos A.
dc.contributor.author
Brugger, Silvio D.
dc.contributor.author
Schuepbach, Reto A.
dc.contributor.author
Kouyos, Roger D.
dc.contributor.author
Hasse, Barbara
dc.contributor.author
Zinkernagel, Annelies S.
dc.date.accessioned
2022-06-20T07:47:18Z
dc.date.available
2022-04-14T08:29:57Z
dc.date.available
2022-04-14T11:35:12Z
dc.date.available
2022-05-05T11:11:45Z
dc.date.available
2022-06-01T11:16:41Z
dc.date.available
2022-06-20T07:47:18Z
dc.date.issued
2022-07
dc.identifier.issn
1470-9465
dc.identifier.issn
1198-743X
dc.identifier.other
10.1016/j.cmi.2022.01.021
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/542418
dc.identifier.doi
10.3929/ethz-b-000542418
dc.description.abstract
Objectives: Difficult-to-treat infections caused by antibiotic-susceptible strains have been linked to the occurrence of persisters, a subpopulation of dormant bacteria that tolerate antibiotic exposure despite lacking genetic resistance. These persisters can be identified phenotypically by plating on nutrient agar because of their altered growth dynamics, resulting in colony-size heterogeneity. The occurrence of within-patient bacterial phenotypic heterogeneity in various infections and clinical determinants of persister formation remains unknown. Methods: We plated bacteria derived from 132 patient samples of difficult-to-treat infections directly on nutrient-rich agar and monitored colony growth by time-lapse imaging. We retained 36 Staphylococcus aureus monocultures for further analysis. We investigated clinical factors associated with increased colony growth-delay with regression analyses. We corroborated the clinical findings using in vitro grown static biofilms exposed to distinct antibiotics. Results: The extent of phenotypic heterogeneity of patient-derived S. aureus varied substantially between patients (from no delay to a maximum of 57.6 hours). Increased heterogeneity coincided with increased median colony growth-delay. Multivariable regression showed that rifampicin treatment was significantly associated with increased median growth-delay (13.3 hours; 95% CI 7.13e19.6 hours; p < 0.001). S. aureus grown in biofilms and exposed to high concentrations of rifampicin or a combination of rifampicin with clindamycin or levofloxacin exhibited prolonged growth-delay (p < 0.05 for 11 of 12 comparisons), correlating with a strain-dependent increase in antibiotic tolerance. Discussion: Colony-size heterogeneity upon direct sampling of difficult-to-treat S. aureus infections was frequently observed. Hence, future studies are needed to assess the potential benefit of phenotypic heterogeneity quantification for staphylococcal infection prognosis and treatment guidelines.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Antibiotic tolerance
en_US
dc.subject
Biofilm
en_US
dc.subject
Phenotypic heterogeneity
en_US
dc.subject
Rifampicin
en_US
dc.subject
Staphylococcus aureus
en_US
dc.title
Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for the presence of persisters across clinical presentations
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2022-02-03
ethz.journal.title
Clinical Microbiology and Infection
ethz.journal.volume
28
en_US
ethz.journal.issue
7
en_US
ethz.journal.abbreviated
Clin Microbiol Infect
ethz.pages.start
1022.e1
en_US
ethz.pages.end
1022.e7
en_US
ethz.size
7 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02720 - Institut für Integrative Biologie / Institute of Integrative Biology::09497 - Hall, Alex / Hall, Alex
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02720 - Institut für Integrative Biologie / Institute of Integrative Biology::09497 - Hall, Alex / Hall, Alex
en_US
ethz.date.deposited
2022-04-14T08:30:07Z
ethz.source
FORM
ethz.eth
no
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-06-20T07:47:24Z
ethz.rosetta.lastUpdated
2023-02-07T03:37:12Z
ethz.rosetta.versionExported
true
ethz.COinS
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