Yersinia pestis High-Pathogenity Island: Mechanisms and Structures responsible for its Dissemination
Final Report Abstract
The Yersinia High-pathogenicity island (HPI) encodes a highly-efficient siderophore yersiniabactin iron uptake. The HPI is an integrative element that is able to occupy any free asn tRNA gene target in bacterial chromosome due to the activity of its site-specific integrase. However, introduction of an additional nucleotide into the critical part of attP (core) by an unknown mechanism and IS100 x IS100 recombination seems to greatly decrease the ability of the HPI to re-integrate in Y. pestis. IntHPI is a bidirectional integrase that promotes both integrative and excisive recombination and the recombination directionality factor (RDF) exhibits only a minor effect on the IntHPI activity in contrast to known effect of the phage Lambda excisionase. IntHPI recognizes asn tRNA genes as its attachment site in attP x attB site-specific recombination. Three other functional recombinases of Ecoc54N, or pks island encoding cytotoxic polyketide colibactin in uropathogenic E. coli CFT073; and two genomic islands with yet unknown functions in Erwinia carotovora, HAI7 and HAI13, also utilize asn tDNA for integration. Although all of the above integrases recognize asn tDNA as a recombination target they are evolutionary divergent both in integrase and attP sequences. This gives a possibility to gain insight into the evolution of the asn tDNA integrases as well as to address protein-DNA recognition in general. Interestingly, only two of the asn tDNA integrases, Inthpi and IntEcocs54, substitute each other in attP x attB recombination of both cognate and non-cognate attP sites, while two other, IntHAI17 and lntHAI13, did not support recombination of heterologous attP sites. Also constructed lntHAi71-99HAi13100-428 chimera was active only with attPHAi17 while lntHAi131-99HAi17100-425 one - only with attPHAi13. This strongly supports our proposal, that the N-terminal domain of the asn tDNA integrases determines their aftP-site specificity. The IntHPi N-terminal domain (residues 1-80) was crystallized to determine its molecular structure. To uncover a mechanism of the inter-bacterial transfer of the HPI, we constructed the RP4'asn "trapping" plasmid that was able to mobilize the complete HPI and to support its transfer to a new bacterial host. Subsequent dissociation of the RP4'asn::HPI cointegrate results in integration of the free HPI into any available asn tDNA site in the host chromosome. We propose a general model in which substituted affB-carrying transmissive plasmids might serve as suitable vehicles for transfer of genomic islands.
Publications
- Horizontal transfer of Yersinia high-pathogenicity island by the conjugative RPAattB target presenting shuttle plasmid. Molecular Microbiology 2005, 57 (3), 727-734
Antonenka, U., Nölting, Ch., J. Heesemann and Rakin A.
- Independent acquisition of site-specific recombination factors by asn tRNA gene-targeting genomic islands. Int J Med Microbiol. 2006 Oct; 296(6):341-52
Antonenka, U., Nölting, Ch., J. Heesemann and Rakin A.
- Factors and Mechanisms of Mobility of the High Pathogenicity Island of Yersinia. Dissertation, LMU München: Fakultät für Biologie, 2007
Antonenka, U.
- Recombination activity of the minimal integrative module of the High-Pathogenicity Island of Yersinia pestis. In: Peste: entre epidemics et societes. Plague: epidemics and societes. Signoli, M., Cheve, D., A., et al eds. 2007, P. 271-275
Rakin, A., Noelting, C , Heesemann, J.
