Publication
Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
| dc.contributor.author | Chung, Marilyn | |
| dc.contributor.author | Borges, Vitor | |
| dc.contributor.author | Gomes, João Paulo | |
| dc.contributor.author | de Lencastre, Herminia | |
| dc.contributor.author | Tomasz, Alexander | |
| dc.date.accessioned | 2019-03-22T15:44:47Z | |
| dc.date.available | 2019-03-22T15:44:47Z | |
| dc.date.issued | 2018-07-03 | |
| dc.description | Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029783/ | |
| dc.description.abstract | Addition of β-lactam antibiotics to growing cultures of bacteria inhibit synthesis of the bacterial cell wall peptidoglycan accompanied by killing (loss of viable titer) and lysis (physical disintegration) of the cells. However, it has also been well established that these antibiotics are not effective in killing non-growing or slow-growing bacteria and the mechanism of this "antibiotic tolerance" is not well understood. In this study, we report on the genetic basis and phenotypic properties of an antibiotic tolerant derivative of the methicillin susceptible S. aureus strain 27s. Cultures were exposed to "pulses" of high concentrations of oxacillin followed by outgrowth of the surviving bacteria. This procedure quickly selected for antibiotic tolerant mutants with an increased ability to survive antibiotic treatment without increase in the MIC value for the antibiotic. Such mutants also exhibited longer lag phase, decreased lysis, virtually no change in antibiotic susceptibilities, cross tolerance to D-cycloserine and vancomycin, and increase in biofilm formation in the presence of high concentrations of oxacillin. Whole genome sequencing showed that these altered properties were linked to mutations in the atl and gdpP genes. | pt_PT |
| dc.description.sponsorship | This work was financially supported by a US Public Health Service Award 2 R01 AI457838- 15 awarded to AT and by funds from the RB Roberts Bacterial Antibiotic Resistance Group (BARG) and by MOSTMICRO Project (LISBOA-01- 0145-FEDER-007660) funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalizac¸ão (POCI); and by national funds through FCT - Fundac¸ão para a Ciência e a Tecnologia and project ONEIDA (LISBOA-01-0145-FEDER-016417) co-funded by FEEI - "Fundos Europeus Estruturais e de Investimento" from "Programa Operacional Regional Lisboa 2020" and by national funds from FCT. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | PLoS One. 2018 Jul 3;13(7):e0199707. doi: 10.1371/journal.pone.0199707. eCollection 2018 | pt_PT |
| dc.identifier.doi | 10.1371/journal.pone.0199707 | pt_PT |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/6278 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Public Library of Science | pt_PT |
| dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199707 | pt_PT |
| dc.subject | Anti-Bacterial Agents | pt_PT |
| dc.subject | Biofilms | pt_PT |
| dc.subject | Drug Resistance, Bacterial | pt_PT |
| dc.subject | Gene Expression Regulation, Bacterial | pt_PT |
| dc.subject | Genome, Bacterial | pt_PT |
| dc.subject | Genotype | pt_PT |
| dc.subject | Microbial Sensitivity Tests | pt_PT |
| dc.subject | Oxacillin | pt_PT |
| dc.subject | Staphylococcal Infections | pt_PT |
| dc.subject | Staphylococcus aureus | pt_PT |
| dc.subject | Whole Genome Sequencing | pt_PT |
| dc.subject | Mutation | pt_PT |
| dc.subject | Phenotype | pt_PT |
| dc.title | Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.issue | 7 | pt_PT |
| oaire.citation.startPage | e0199707 | pt_PT |
| oaire.citation.title | PLoS ONE | pt_PT |
| oaire.citation.volume | 13 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |