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Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant

Lookup NU author(s): Dr Nhat Khai Bui, Dr Joseph Gray, Professor Waldemar Vollmer


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Beta-lactam resistant clinical isolates of Streptococcus pneumoniae contain altered penicillin-binding protein (PBP) genes and occasionally an altered murM, presumably products of interspecies gene transfer. MurM and MurN are responsible for the synthesis of branched lipid II, substrate for the PBP catalyzed transpeptidation reaction. Here we used the high-level beta-lactam resistant S.oralisUo5 as donor in transformation experiments with the sensitive laboratory strain S.pneumoniae R6 as recipient. Surprisingly, piperacillin-resistant transformants contained no alterations in PBP genes but carried murE(Uo5) encoding the UDP-N-acetylmuramyl tripeptide synthetase. Codons 83-183 of murE(Uo5) were sufficient to confer the resistance phenotype. Moreover, the promoter of murE(Uo5), which drives a twofold higher expression compared to that of S.pneumoniae R6, could also confer increased resistance. Multiple independent transformations produced S.pneumoniaeR6 derivatives containing murE(Uo5), pbp2x(Uo5), pbp1a(Uo5) and pbp2b(Uo5), but not murM(Uo5) sequences; however, the resistance level of the donor strain could not be reached. S.oralisUo5 harbors an unusual murM, and murN is absent. Accordingly, the peptidoglycan of S.oralisUo5 contained interpeptide bridges with one L-Ala residue only. The data suggest that resistance in S.oralisUo5 is based on a complex interplay of distinct PBPs and other enzymes involved in peptidoglycan biosynthesis.

Publication metadata

Author(s): Todorova K, Maurer P, Rieger M, Becker T, Bui NK, Gray J, Vollmer W, Hakenbeck R

Publication type: Article

Publication status: Published

Journal: Molecular Microbiology

Year: 2015

Volume: 97

Issue: 5

Pages: 866-880

Print publication date: 01/09/2015

Online publication date: 19/06/2015

Acceptance date: 21/05/2015

ISSN (print): 0950-382X

ISSN (electronic): 1365-2958

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/mmi.13070


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Funder referenceFunder name
EC through the DIVINOCELL project
Ha1011/11-1Deutsche Forschungsgemeinschaft
Ha1011/11-2Deutsche Forschungsgemeinschaft