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Antimicrobial Agents and Chemotherapy, May 2009, p. 2034-2041, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01485-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

An ABC Transporter of Streptococcus pneumoniae Involved in Susceptibility to Vancoresmycin and Bacitracin{triangledown}

Petra Becker, Regine Hakenbeck, and Bernhard Henrich*

Fachbereich Biologie, Abteilung Mikrobiologie, Technische Universität Kaiserslautern, Gottlieb-Daimler-Strasse, D-67663 Kaiserslautern, Germany

Received 6 November 2008/ Returned for modification 7 January 2009/ Accepted 2 March 2009

Vancoresmycin is a novel tetramic acid antibiotic, probably interfering with functions of the cytoplasmic membrane. To investigate its mode of action, mutants of Streptococcus pneumoniae exhibiting reduced susceptibility to vancoresmycin were isolated at a low frequency. Four of them were further examined and showed similar pleiotropic phenotypes, including reduced growth rate, early autolysis, and chain formation. In one mutant, the level of transcripts from a single locus encoding the potential ABC transporter Spr0812-Spr0813 was increased sixfold. The corresponding DNA sequence revealed a nonsense mutation (C1744T) in spr0813, leading to the formation of a truncated permease lacking 2 of the 10 predicted transmembrane helices. As demonstrated by deletion and transformation analysis and reconstructing the spr0813C1744T mutation in the wild-type background, this nucleotide exchange was sufficient to cause reduced susceptibility to vancoresmycin and higher amounts of spr0812-spr0813 mRNA. Mapping and reporter assays of the cognate promoter Pabc showed that spr0812 and spr0813 are cotranscribed with a preceding small gene and that the spr0813C1744T mutation does not affect the activity of Pabc. Due to the similarity of Spr0812-Spr0813 to bacitracin transporters of Streptococcus mutans and Bacillus spp., the bacitracin susceptibility of spr0813 mutants was examined. Both the spr0813C1744T nonsense mutation and the deletion of the transporter genes led to a clearly increased sensitivity to bacitracin. Thus, the intact transporter is required for intrinsic resistance to bacitracin, whereas reduced vancoresmycin susceptibility is mediated by the truncated permease.

* Corresponding author. Mailing address: Fachbereich Biologie, Abteilung Mikrobiologie, Technische Universität Kaiserslautern, P.O. Box 3049, 67653 Kaiserslautern, Germany. Phone: 49-(0)631-2052347. Fax: 49-(0)631-2053799. E-mail: henrich{at}rhrk.uni-kl.de

{triangledown} Published ahead of print on 9 March 2009.

Antimicrobial Agents and Chemotherapy, May 2009, p. 2034-2041, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01485-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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