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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A mutation in the glycosyltransferase gene lafB causes daptomycin hypersusceptibility in Enterococcus faecium

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Author(s):
Mello, Suelen S. [1, 2, 3, 4, 5] ; Van Tyne, Daria [6, 7, 8] ; Lebreton, Francois [6, 8] ; Silva, Simone Q. [9, 10] ; Nogueira, Mara C. L. [9] ; Gilmore, Michael S. [6, 8] ; Camargo, Ilana L. B. C. [2]
Total Authors: 7
Affiliation:
[1] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 - USA
[2] Univ Sao Paulo, Sao Carlos Inst Phys, Sao Carlos - Brazil
[3] Univ Fed Sao Carlos, Sao Carlos - Brazil
[4] Harvard Med Sch, Dept Ophthalmol, Boston, MA 02115 - USA
[5] Harvard Med Sch, Dept Immunobiol, Boston, MA 02115 - USA
[6] Harvard Med Sch, Boston, MA 02115 - USA
[7] Univ Pittsburgh, Sch Med, Div Infect Dis, 3550 Terrace St, Pittsburgh, PA - USA
[8] Massachusetts Eye & Ear Infirm, Boston, MA 02114 - USA
[9] Fac Med Sao Jose Do Rio Preto FAMERP, Dept Doencas Dermatol Infecciosas & Parasitarias, Sao Jose Do Rio Preto - Brazil
[10] UNESP, Inst Biociencias Letras & Ciencias Exatas IBILCE, Sao Jose Do Rio Preto - Brazil
Total Affiliations: 10
Document type: Journal article
Source: Journal of Antimicrobial Chemotherapy; v. 75, n. 1, p. 36-45, JAN 2020.
Web of Science Citations: 0
Abstract

Objectives: To verify dissemination of daptomycin-non-susceptible Enterococcus faecium in a hospital where daptomycin was not in use and to understand the evolutionary pathways connecting daptomycin hypersusceptibility to non-susceptibility. Methods: Clonality of 26 E. faecium was assessed by PFGE and the STs of these isolates were determined. The most daptomycin-susceptible isolate was evolved in vitro by stepwise daptomycin selection, generating isolates for genome comparisons. Results: The spread of a high-risk daptomycin-non-susceptible VRE clone was detected, as was the occurrence of an unusual daptomycin-hypersusceptible strain (HBSJRP18). To determine the basis for daptomycin hypersusceptibility, we evolved HBSJRP18 in vitro and identified candidate genetic alterations potentially related to daptomycin susceptibility. Both lafB, encoding glycosyl-transferase, which is putatively involved in Lipoteichoic acid (LTA) biosynthesis, and dak, encoding a dihydroxyacetone kinase likely involved in fatty acid metabolism, were mutated in multiple independent experiments. Trans-complementation showed that the lafB polymorphism naturally occurring in HBSJRP18 caused its daptomycin hypersusceptibility. Fourier-transform infrared spectroscopy identified differences between the extracted LTA spectra from the hypersusceptible isolate and its revertant, as well as other non-susceptible variants, supporting a role for LafB in E. faecium LTA biosynthesis. Zeta potential difference was detected in one evolved dak mutant derivative. While much more susceptible to daptomycin, HBSJRP18 showed enhanced growth in the presence of piperacillin, suggesting that this, or another cell wall-targeting antibiotic, may have selected for the daptomycin-hypersusceptible phenotype. Conclusions: Our findings provide new information on the basis for daptomycin susceptibility in E. faecium, with implications for Limiting the development and spread of daptomycin resistance. (AU)

FAPESP's process: 16/23810-6 - Study of alternative pathways to the LiaFSR and YycFGHIJ systems that lead to the decrease of Daptomycin susceptibility in Enterococcus faecium
Grantee:Ilana Lopes Baratella da Cunha Camargo
Support Opportunities: Regular Research Grants