The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA
Open accessAbstract
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple β-lactam combination meropenem/piperacillin/tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA N315 and 72 clinical MRSA isolates in vitro, and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents. We demonstrate that these activities also extend to other carbapenem/penicillin/β-lactamase inhibitor combinations. ME/PI/TZ circumvents the tight regulation of the mec and bla operons in MRSA, the basis for inducible resistance to β-lactam antibiotics. Furthermore, ME/PI/TZ subverts the function of penicillin-binding protein 2a (PBP2a) action via allostery, which we propose as the mechanism for both synergy and collateral sensitivity. Showing similar in vivo activity to linezolid, ME/PI/TZ demonstrates that combinations of older β-lactam antibiotics could be effective against MRSA infections in humans.
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Citations
Cites
Waves of resistance: Staphylococcus aureus in the antibiotic era
Chambers, H. F., & DeLeo, F. R. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2200 · Cited by 2,718
Cited by
β-Lactams and β-Lactamase Inhibitors: An Overview
Bush, K., & Bradford, P. A. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025247 · Cited by 1,412
Multidrug evolutionary strategies to reverse antibiotic resistance
Baym, M., Stone, L. K., & Kishony, R. (2016) · Science · doi:10.1126/science.aad3292 · Cited by 710
The rapid spread of carbapenem-resistant Enterobacteriaceae
Potter, R. F., D’Souza, A. W., & Dantas, G. (2016) · Drug Resistance Updates · doi:10.1016/j.drup.2016.09.002 · Cited by 403
Self-citationAntibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides
Lázár, V., Martins, A., Spohn, R., Daruka, L., Grézal, G., Fekete, G., Számel, M., Jangir, P. K., Kintses, B., Csörgő, B., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0164-0 · Cited by 375
Antibiotic resistance: turning evolutionary principles into clinical reality
Andersson, D. I., Balaban, N. Q., Baquero, F., Courvalin, P., Glaser, P., Gophna, U., Kishony, R., Molin, S., & Tønjum, T. (2020) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaa001 · Cited by 238
Metadata
- Authors
- Gonzales, P. R., Pesesky, M. W., Bouley, R., Ballard, A., Biddy, B. A., Suckow, M. A., Wolter, W. R., Schroeder, V. A., Burnham, C.-A. D., Mobashery, S., Chang, M., & Dantas, G.
- Venue
- Nature Chemical Biology
- Published
- 2015-09-14
- Volume
- 11
- Issue
- 11
- Pages
- 855-861
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2107676192
- Cited by
- 160
- References
- 1
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Gonzales, P. R., Pesesky, M. W., Bouley, R., Ballard, A., Biddy, B. A., Suckow, M. A., Wolter, W. R., Schroeder, V. A., Burnham, C.-A. D., Mobashery, S., Chang, M., & Dantas, G. (2015). Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA. Nature Chemical Biology. https://doi.org/10.1038/nchembio.1911
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