Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii

Marta Martínez-Guitián; Juan C. Vázquez-Ucha; Joshua Odingo; Tanya Parish; Margarita Poza; Richard D. Waite; German Bou; David W. Wareham; Alejandro Beceiro

doi:10.1128/AAC.00510-16

Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii

Marta Martínez-Guitián
, Juan C. Vázquez-Ucha
, Joshua Odingo
, Tanya Parish
, Margarita Poza
, Richard D. Waite
, German Bou
, David W. Wareham
, Alejandro Beceiro

Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC)
Infectious Disease Research Institute
TB Discovery Research
Queen Mary University of London

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FIC_index] = 0.13 to 0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of lipid A (FICindex = 0.14 to 0.25) but not against colistin-resistant Δlpx strains with loss of lipopolysaccharide (FIC_index = 0.75 to 1). A colistin/MD3 combination would need to be targeted to strains with specific colistin resistance mechanisms.

Original language	English
Pages (from-to)	4375-4379
Number of pages	5
Journal	Antimicrobial Agents and Chemotherapy
Volume	60
Issue number	7
DOIs	https://doi.org/10.1128/AAC.00510-16
Publication status	Published - 20 Jun 2016
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1128/AAC.00510-16

Cite this

Martínez-Guitián, M., Vázquez-Ucha, J. C., Odingo, J., Parish, T., Poza, M., Waite, R. D., Bou, G., Wareham, D. W., & Beceiro, A. (2016). Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy, 60(7), 4375-4379. https://doi.org/10.1128/AAC.00510-16

@article{11f3485f7ecb486a923707389acbd4fb,

title = "Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii",

abstract = "Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FICindex] = 0.13 to 0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of lipid A (FICindex = 0.14 to 0.25) but not against colistin-resistant Δlpx strains with loss of lipopolysaccharide (FICindex = 0.75 to 1). A colistin/MD3 combination would need to be targeted to strains with specific colistin resistance mechanisms.",

author = "Marta Mart{\'i}nez-Guiti{\'a}n and V{\'a}zquez-Ucha, \{Juan C.\} and Joshua Odingo and Tanya Parish and Margarita Poza and Waite, \{Richard D.\} and German Bou and Wareham, \{David W.\} and Alejandro Beceiro",

year = "2016",

month = jun,

day = "20",

doi = "10.1128/AAC.00510-16",

language = "English",

volume = "60",

pages = "4375--4379",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "7",

}

Martínez-Guitián, M, Vázquez-Ucha, JC, Odingo, J, Parish, T, Poza, M, Waite, RD, Bou, G, Wareham, DW & Beceiro, A 2016, 'Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii', Antimicrobial Agents and Chemotherapy, vol. 60, no. 7, pp. 4375-4379. https://doi.org/10.1128/AAC.00510-16

Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii. / Martínez-Guitián, Marta; Vázquez-Ucha, Juan C.; Odingo, Joshua et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 7, 20.06.2016, p. 4375-4379.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii

AU - Martínez-Guitián, Marta

AU - Vázquez-Ucha, Juan C.

AU - Odingo, Joshua

AU - Parish, Tanya

AU - Poza, Margarita

AU - Waite, Richard D.

AU - Bou, German

AU - Wareham, David W.

AU - Beceiro, Alejandro

PY - 2016/6/20

Y1 - 2016/6/20

N2 - Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FICindex] = 0.13 to 0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of lipid A (FICindex = 0.14 to 0.25) but not against colistin-resistant Δlpx strains with loss of lipopolysaccharide (FICindex = 0.75 to 1). A colistin/MD3 combination would need to be targeted to strains with specific colistin resistance mechanisms.

AB - Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of Acinetobacter baumannii isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FICindex] = 0.13 to 0.24) and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of lipid A (FICindex = 0.14 to 0.25) but not against colistin-resistant Δlpx strains with loss of lipopolysaccharide (FICindex = 0.75 to 1). A colistin/MD3 combination would need to be targeted to strains with specific colistin resistance mechanisms.

U2 - 10.1128/AAC.00510-16

DO - 10.1128/AAC.00510-16

M3 - Article

C2 - 27139471

AN - SCOPUS:84977103509

SN - 0066-4804

VL - 60

SP - 4375

EP - 4379

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 7

ER -

Synergy between colistin and the signal peptidase inhibitor MD3 is dependent on the mechanism of colistin resistance in Acinetobacter baumannii

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this