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Antimicrobial Agents and Chemotherapy, November 2009, p. 4702-4711, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00439-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Large Mechanosensitive Channel MscL Determines Bacterial Susceptibility to the Bacteriocin Sublancin 168{triangledown}

Thijs R. H. M. Kouwen, Erik N. Trip, Emma L. Denham, Mark J. J. B. Sibbald, Jean-Yves F. Dubois, and Jan Maarten van Dijl*

Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands

Received 31 March 2009/ Returned for modification 31 July 2009/ Accepted 28 August 2009

Bacillus subtilis strain 168 produces the extremely stable and broad-spectrum lantibiotic sublancin 168. Known sublancin 168-susceptible organisms include important pathogens, such as Staphylococcus aureus. Nevertheless, since its discovery, the mode of action of sublancin 168 has remained elusive. The present studies were, therefore, aimed at the identification of cellular determinants for bacterial susceptibility toward sublancin 168. Growth inhibition and competition assays on plates and in liquid cultures revealed that sublancin 168-mediated growth inhibition of susceptible B. subtilis and S. aureus cells is affected by the NaCl concentration in the growth medium. Added NaCl did not influence the production, activity, or stability of sublancin 168 but, instead, lowered the susceptibility of sensitive cells toward this lantibiotic. Importantly, the susceptibility of B. subtilis and S. aureus cells toward sublancin 168 was shown to depend on the presence of the large mechanosensitive channel of conductance MscL. In contrast, MscL was not involved in susceptibility toward the bacteriocin nisin or Pep5. Taken together, our unprecedented results demonstrate that MscL is a critical and specific determinant in bacterial sublancin 168 susceptibility that may serve either as a direct target for this lantibiotic or as a gate of entry to the cytoplasm.

* Corresponding author. Mailing address: Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Phone: 31-50-3615187. Fax: 31-50-3619105. E-mail: J.M.van.Dijl{at}med.umcg.nl

{triangledown} Published ahead of print on 8 September 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4702-4711, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00439-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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