Phenotypic and genetic changes associated with the seesaw effect in MRSA strain N315 in a bioreactor model.

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dc.contributor.authorMishra, Smruti*
dc.contributor.authorLasek-Nesselquist, Erica*
dc.contributor.authorMathur, Anarv*
dc.contributor.authorMa, Zhuo
dc.contributor.authorBoonthaworn, Kanpong
dc.contributor.authorO'Donnell, J Nicholas
dc.contributor.authorSui, Haixin
dc.contributor.authorPata, Janice D
dc.contributor.authorMcDonough, Kathleen A
dc.contributor.authorJayachandran, Pradeepa
dc.contributor.authorMalik, Meenakshi
dc.contributor.orcidhttps://orcid.org/0000-0001-5184-1385
dc.date.accessioned2023-12-01T16:35:01Z
dc.date.available2023-12-01T16:35:01Z
dc.date.issued1/24/2022
dc.descriptionClick on the Resource Link to access the article (may not be free).en_US
dc.description.abstractObjectives: Over the past decade, daptomycin treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections has led to the emergence of daptomycin non-susceptible (DAP-NS) MRSA strains and a subsequent interest in combinatorial antibiotic therapies. We investigated the phenotypic and genetic changes associated with the seesaw effect, which describes the correlation between daptomycin resistance and increased beta-lactam susceptibility in DAP-NS MRSA and the reverse phenomenon of DAP-NS strains acquiring renewed susceptibility to daptomycin after beta-lactam exposure. Methods: A continuous bioreactor model was used to study the effects of incremental doses of daptomycin followed by oxacillin on MRSA strain N315. MICs for daptomycin and oxacillin were determined for the bioreactor-derived samples. Transmission electron microscopy and cytochrome C binding assays were used to measure cell wall thickness and cell membrane charge, respectively, in the bioreactor-derived samples. Whole-genome sequencing was used to identify mutations associated with seesaw effect. Results: While daptomycin resistance conferred enhanced susceptibility to oxacillin, oxacillin treatment of DAP-NS strains was accompanied by a lowered MIC for daptomycin. Additionally, there was a reduction in relative positive cell surface charge and cell wall thickness. However, the mutations acquired in our DAP-NS populations were not accompanied by additional genomic changes after treatment with oxacillin, implicating alternative mechanisms for the seesaw effect. Conclusion: In this study, we successfully produced and characterized the seesaw effect in MRSA strain N315 in a unique bioreactor model.
dc.description.urihttps://doi.org/10.1016/j.jgar.2022.01.013en_US
dc.identifier.citationMishra S, Lasek-Nesselquist E, Mathur A, Ma Z, Boonthaworn K, O'Donnell N, Sui H, Pata JD, McDonough KA, Jayachandran P, Malik M. Phenotypic and genetic changes associated with the seesaw effect in MRSA strain N315 in a bioreactor model. J Glob Antimicrob Resist. 2022 Jan 24:S2213-7165(22)00017-0. doi: 10.1016/j.jgar.2022.01.013. Epub ahead of print. PMID: 35085792.en_US
dc.identifier.issn2213-7165
dc.identifier.other35085792
dc.identifier.urihttps://hdl.handle.net/20.500.14303/452
dc.language.isoenen_US
dc.publisherInternational Society of Chemotherapy for Infection and Cancer
dc.relation.ispartofJournal of Global Antimicrobial Resistance
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). http://rightsstatements.org/vocab/InC/1.0/
dc.subjectCell Surface Chargeen_US
dc.subjectCell Wall Thicknessen_US
dc.subjectDaptomycin non-susceptibilityen_US
dc.subjectMRSAen_US
dc.subjectSeesaw Effecten_US
dc.titlePhenotypic and genetic changes associated with the seesaw effect in MRSA strain N315 in a bioreactor model.
dc.typeArticleen_US
local.departmentprogramDepartment of Life Sciences
local.departmentprogramDepartment of Pharmacy Practice
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