New Molecular Solutions in Research and Development for Innovative Drugs

Structure and Function of a Bacterial Type IV Sectretion System (T4SS)

Walter Keller, Institut für Molekulare Biowissenschaften, Karl Franzens Universität

Conjugative plasmid transfer is the most important means of spreading antibiotic resistance and virulence genes among bacteria and therefore presents a serious threat to human health. To date most well studied conjugative type IV secretion systems (T4SS) are of Gram-negative origin. Although many medically relevant pathogens are Gram-positive, their conjugation systems have received little attention so far.

We have studied the conjugation system of the multiple antibiotic resistance plasmid pIP501, which exhibits the broadest known host range for plasmid transfer in Gram-positive bacteria including enterococci, staphylococci and streptococci [1, 2]. Its transfer region is organized in an operon encoding fifteen putative transfer proteins. We have recently crystallized three of the conjugation proteins, TraK, TraM and TraN and solved their structures [3-5]. The proteins are either putative members oft the T4SS core complex and/or fulfill a scaffolding function for building up the secretion machinery. In addition the TraN protein is binding double strand DNA. In this paper we present the structures oft the conjugation proteins and their putative roles in the construction of the conjugation system.

[1]  Grohmann, E., Muth, G., and Espinosa, M. (2003) Microbiol. Mol. Biol. Rev. 67, 277–301.
[2]  Goessweiner-Mohr, N., K. Arends,, W. Keller, and E. Grohmann, (2013) Plasmid 70, 289-302.
[3]  Goessweiner-Mohr, N., C. Fercher, M. Y. Abajy, E. Grohmann, and W. Keller. (2012) Acta Crystallogr. Sect. F 68, 1402-1405.
[4]  Goessweiner-Mohr, C. Fercher, K. Arends,, R. Birner-Gruenberger, D. Laverde-Gomez, J. Huebner, E. Grohmann, and W. Keller, (2014) Acta Crystallogr. Sect. D,  in press.
[5]  Goessweiner-Mohr, N., L. Grumet, K. Arends, T. Pavkov-Keller, C. C. Gruber, K. Gruber, R. Birner-Gruenberger, A. Kropec-Huebner, J. Huebner, E. Grohmann, and W. Keller. (2013) J. Biol. Chem. 288, 2018-2028.