Heterologous Protein Expression Favors the Formation of Protein Aggregates in Persister and Viable but Nonculturable Bacteria
dc.contributor.author | Goode, O | |
dc.contributor.author | Smith, A | |
dc.contributor.author | Łapińska, U | |
dc.contributor.author | Bamford, R | |
dc.contributor.author | Kahveci, Z | |
dc.contributor.author | Glover, G | |
dc.contributor.author | Attrill, E | |
dc.contributor.author | Carr, A | |
dc.contributor.author | Metz, J | |
dc.contributor.author | Pagliara, S | |
dc.date.accessioned | 2021-05-28T08:28:26Z | |
dc.date.issued | 2021-05-17 | |
dc.description.abstract | Environmental and intracellular stresses can perturb protein homeostasis and trigger the formation and accumulation of protein aggregates. It has been recently suggested that the level of protein aggregates accumulated in bacteria correlates with the frequency of persister and viable but nonculturable cells that transiently survive treatment with multiple antibiotics. However, these findings have often been obtained employing fluorescent reporter strains. This enforced heterologous protein expression facilitates the visualization of protein aggregates but could also trigger the formation and accumulation of protein aggregates. Using microfluidics-based single-cell microscopy and a library of green fluorescent protein reporter strains, we show that heterologous protein expression favors the formation of protein aggregates. We found that persister and viable but nonculturable bacteria surviving treatment with antibiotics are more likely to contain protein aggregates and downregulate the expression of heterologous proteins. Our data also suggest that such aggregates are more basic with respect to the rest of the cell. These findings provide evidence for a strong link between heterologous protein expression, protein aggregation, intracellular pH, and phenotypic survival to antibiotics, suggesting that antibiotic treatments against persister and viable but nonculturable cells could be developed by modulating protein aggregation and pH regulation. | en_GB |
dc.description.sponsorship | The Royal Society | en_GB |
dc.description.sponsorship | Marie Skłodowska‐Curie | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | The Gordon and Betty Moore Foundation | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Engineering and Physical Sciences Research Council (EPSRC) | en_GB |
dc.description.sponsorship | University of Exeter | en_GB |
dc.description.sponsorship | DSTL | en_GB |
dc.identifier.citation | Published online 17 May 2021 | en_GB |
dc.identifier.doi | 10.1021/acsinfecdis.1c00154 | |
dc.identifier.grantnumber | RG180007 | en_GB |
dc.identifier.grantnumber | H2020-MSCA-ITN-2015–675752 | en_GB |
dc.identifier.grantnumber | BB/M009122/1 | en_GB |
dc.identifier.grantnumber | MCPC17189 | en_GB |
dc.identifier.grantnumber | GBMF5514 | en_GB |
dc.identifier.grantnumber | MR/P016162/1 | en_GB |
dc.identifier.grantnumber | EP/M506527/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/125855 | |
dc.language.iso | en | en_GB |
dc.publisher | American Chemical Society | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/34000805 | en_GB |
dc.rights | © 2021 The Authors. Published by American Chemical Society | en_GB |
dc.subject | antimicrobial resistance | en_GB |
dc.subject | heterologous expression | en_GB |
dc.subject | microfluidics | en_GB |
dc.subject | persisters | en_GB |
dc.subject | protein aggregation | en_GB |
dc.subject | viable but nonculturable cells | en_GB |
dc.title | Heterologous Protein Expression Favors the Formation of Protein Aggregates in Persister and Viable but Nonculturable Bacteria | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-05-28T08:28:26Z | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final version. Available from the American Chemical Society via the DOI in this record. | en_GB |
dc.identifier.journal | ACS Infectious Diseases | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-05-17 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-05-28T08:17:32Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2021-05-28T08:28:32Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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