Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

Emily Lythell; Reynier Suardiaz Del Rio; Philip Hinchliffe; Chonnikan Hanpaibool; Surawit  Visitsatthawong; A. Sofia. F Oliveira; Eric J M Lang; Panida Surawatanawong; Vannajan Sanghiran Lee; Thanyada Rungrotmongkol; Natalie Fey; James Spencer; Adrian J Mulholland

doi:10.1039/D0CC02520H

Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

Emily Lythell, Reynier Suardiaz Del Rio, Philip Hinchliffe, Chonnikan Hanpaibool, Surawit Visitsatthawong, A. Sofia. F Oliveira, Eric J M Lang, Panida Surawatanawong, Vannajan Sanghiran Lee, Thanyada Rungrotmongkol, Natalie Fey, James Spencer^*, Adrian J Mulholland^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal)

Abstract

MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the “last-resort” antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.

Original language	English
Pages (from-to)	6874-6877
Number of pages	4
Journal	Chemical Communications
Volume	50
Early online date	6 May 2020
DOIs	https://doi.org/10.1039/D0CC02520H
Publication status	Published - 25 Jun 2020

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Lythell, E., Suardiaz Del Rio, R., Hinchliffe, P., Hanpaibool, C., Visitsatthawong, S., Oliveira, A. S. F., Lang, E. J. M., Surawatanawong, P., Sanghiran Lee, V., Rungrotmongkol, T., Fey, N., Spencer, J., & Mulholland, A. J. (2020). Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes. Chemical Communications, 50, 6874-6877 . https://doi.org/10.1039/D0CC02520H

Lythell, Emily ; Suardiaz Del Rio, Reynier ; Hinchliffe, Philip ; Hanpaibool, Chonnikan ; Visitsatthawong, Surawit ; Oliveira, A. Sofia. F ; Lang, Eric J M ; Surawatanawong, Panida ; Sanghiran Lee, Vannajan ; Rungrotmongkol, Thanyada ; Fey, Natalie ; Spencer, James ; Mulholland, Adrian J. / Resistance to the “Last Resort” Antibiotic Colistin : A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes. In: Chemical Communications. 2020 ; Vol. 50. pp. 6874-6877 .

@article{1112f712e02a4954bf833cff007af812,

title = "Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes",

abstract = "MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the “last-resort” antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.",

author = "Emily Lythell and {Suardiaz Del Rio}, Reynier and Philip Hinchliffe and Chonnikan Hanpaibool and Surawit Visitsatthawong and Oliveira, {A. Sofia. F} and Lang, {Eric J M} and Panida Surawatanawong and {Sanghiran Lee}, Vannajan and Thanyada Rungrotmongkol and Natalie Fey and James Spencer and Mulholland, {Adrian J}",

year = "2020",

month = jun,

day = "25",

doi = "10.1039/D0CC02520H",

language = "English",

volume = "50",

pages = " 6874--6877 ",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

}

Lythell, E, Suardiaz Del Rio, R, Hinchliffe, P, Hanpaibool, C, Visitsatthawong, S, Oliveira, ASF, Lang, EJM, Surawatanawong, P, Sanghiran Lee, V, Rungrotmongkol, T, Fey, N , Spencer, J & Mulholland, AJ 2020, 'Resistance to the “Last Resort” Antibiotic Colistin: A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes', Chemical Communications, vol. 50, pp. 6874-6877 . https://doi.org/10.1039/D0CC02520H

Resistance to the “Last Resort” Antibiotic Colistin : A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes. / Lythell, Emily; Suardiaz Del Rio, Reynier; Hinchliffe, Philip; Hanpaibool, Chonnikan; Visitsatthawong, Surawit ; Oliveira, A. Sofia. F; Lang, Eric J M; Surawatanawong, Panida; Sanghiran Lee, Vannajan; Rungrotmongkol, Thanyada; Fey, Natalie ; Spencer, James ; Mulholland, Adrian J.

In: Chemical Communications, Vol. 50, 25.06.2020, p. 6874-6877 .

Research output: Contribution to journal › Article (Academic Journal)

TY - JOUR

T1 - Resistance to the “Last Resort” Antibiotic Colistin

T2 - A Single-Zinc Mechanism for Phosphointermediate Formation in MCR Enzymes

AU - Lythell, Emily

AU - Suardiaz Del Rio, Reynier

AU - Hinchliffe, Philip

AU - Hanpaibool, Chonnikan

AU - Visitsatthawong, Surawit

AU - Oliveira, A. Sofia. F

AU - Lang, Eric J M

AU - Surawatanawong, Panida

AU - Sanghiran Lee, Vannajan

AU - Rungrotmongkol, Thanyada

AU - Fey, Natalie

AU - Spencer, James

AU - Mulholland, Adrian J

PY - 2020/6/25

Y1 - 2020/6/25

N2 - MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the “last-resort” antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.

AB - MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the “last-resort” antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.

U2 - 10.1039/D0CC02520H

DO - 10.1039/D0CC02520H

M3 - Article (Academic Journal)

VL - 50

SP - 6874

EP - 6877

JO - Chemical Communications

JF - Chemical Communications

SN - 1359-7345

ER -