Article (Scientific journals)
Type M resistance to macrolides is due to a two-gene efflux transport system of the ATP-binding cassette (ABC) superfamily
Iannelli, F.; Santoro, F.; Santagati, M. et al.
2018In Frontiers in Microbiology, 9, p. 1-9
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Keywords :
ABC transporter; Macrolide efflux; Mef(A); Msr(D); Prophage; Streptococcus pneumoniae; Streptococcus pyogenes; Article
Abstract :
[en] The mef(A) gene was originally identified as the resistance determinant responsible for type M resistance to macrolides, a phenotype frequently found in clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes. MefA was defined as a secondary transporter of the major facilitator superfamily driven by proton-motive force. However, when characterizing the mef(A)-carrying elements Tn1207.1 and 1207.3, another macrolide resistance gene, msr(D), was found adjacent to mef(A). To define the respective contribution of mef(A) and msr(D) to macrolide resistance, three isogenic deletion mutants were constructed by transformation of a S. pneumoniae strain carrying 1207.3: (i) mef(A)-msr(D); (ii) mef(A)-msr(D); and (iii) mef(A)-msr(D). Susceptibility testing of mutants clearly showed that msr(D) is required for macrolide resistance, while deletion of mef(A) produced only a twofold reduction in the minimal inhibitory concentration (MIC) for erythromycin. The contribution of msr(D) to macrolide resistance was also studied in S. pyogenes, which is the original host of 1207.3. Two isogenic strains of S. pyogenes were constructed: (i) FR156, carrying 1207.3, and (ii) FR155, carrying 1207.3/msr(D). FR155 was susceptible to erythromycin, whereas FR156 was resistant, with an MIC value of 8 g/ml. Complementation experiments showed that reintroduction of the msr(D) gene could restore macrolide resistance in msr(D) mutants. Radiolabeled erythromycin was retained by strains lacking msr(D), while msr(D)-carrying strains showed erythromycin efflux. Deletion of mef(A) did not affect erythromycin efflux. This data suggest that type M resistance to macrolides in streptococci is due to an efflux transport system of the ATP-binding cassette (ABC) superfamily, in which mef(A) encodes the transmembrane channel, and msr(D) the two ATP-binding domains. © 2018 Frontiers Media S.A. All rights reserved.
Disciplines :
Microbiology
Author, co-author :
Iannelli, F.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Santoro, F.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Santagati, M.;  Section of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Docquier, Jean-Denis ;  Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines
Lazzeri, E.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Pastore, G.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Cassone, M.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Oggioni, M. R.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Rossolini, G. M.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Stefani, S.;  Section of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
Pozzi, G.;  Department of Medical Biotechnologies, University of Siena, Siena, Italy
Language :
English
Title :
Type M resistance to macrolides is due to a two-gene efflux transport system of the ATP-binding cassette (ABC) superfamily
Publication date :
2018
Journal title :
Frontiers in Microbiology
eISSN :
1664-302X
Publisher :
Frontiers Media S.A.
Volume :
9
Pages :
1-9
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Grants ANTIRESDEV HEALTH-F3-2009-241446; Project PRIN 2012 (2012WJSX8K)
Funders :
CE - Commission Européenne [BE]
MIUR - Ministero dell'Istruzione, dell'Università e della Ricerca [IT]
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