Molecular and Cellular Microbiology

Angeles Zorreguieta - Fundación Instituto Leloir


Molecular and Cellular Microbiology

Our goal is contribute to the understanding of how certain bacteria that are relevant for agriculture or health are capable to colonize the various niches they inhabit. We are particularly interested to determine the molecular bases of biofilm formation and adhesion to the host in species of the alpha-proteobacteria group, such as Rhizobium and Brucella. Rhizobium is a legume symbiont that is very beneficial for the plant due to its ability to fix the atmospheric nitrogen. Brucella is a close relative of Rhizobium. However, the interaction with the host results in a zoonotic disease called brucellosis, which affects cattle, pigs, and sheep, causing significant economic losses in several countries of our region.
  • Biofilms of Rhizobium. Biofilms are aggregates of microorganisms embedded in an extracellular matrix composed of polymers that the same bacteria produce. The ability to develop these communities provides a competitive advantage for the colonization of biotic or abiotic surfaces. Rhizobium leguminosarum develops a typical biofilm structure in a process mediated by the acidic exopolysaccharide (EPS), the O antigen of the LPS, and proteins secreted by the type I PrsDE system. Recently, we demonstrated that one of such proteins, RapA2, exhibits a structure similar to eukaryotic cadherins that is capable to interact specifically with the EPS of Rhizobium. Since RapA2 and most PrsDE secreted proteins possess at least one cadherin-like domain, we propose that these proteins participate in the modulation of the extracellular matrix composed mainly by the EPS. We are interested to elucidate the role of other proteins whose secretion is PrsDE-dependent, as well as the interplay between the different extracellular factors involved in biofilm formation.
  • Adhesins of Brucella. Brucella is a facultative intracellular pathogen that affects livestock animals and humans. The currently available vaccines are not completely efficient to prevent the disease in livestock and no vaccine for human brucellosis has been developed yet. The intracellular trafficking of this bacterium and the factors required to reach the replicative niche have been considerably studied and understood. However, little is known about the bacterial factors involved in the initial interaction with the host cell. Recently, we identified several proteins from the autotransporter families that participate in the Brucella suis adhesion to extracellular matrix components and host cells. The monomeric autotranspotador BmaC is involved in the binding of B. suis to host cells through fibronectin. In addition, the BtaE trimeric autotransporter showed affinity for hyaluronic acid and it was required both to efficiently bind host cells and for a complete virulence phenotype in the mouse model. Interestingly, both BtaE and BmaC were shown to localize at the new pole of the bacterium, which defines this pole as "adhesive".

Bialer MG (*), Ruiz-Ranwez V (*), Sycz  G, Estein S, Russo DM, Altabe S, Siera R, Zorreguieta A. MapB, the Brucella suis TamB homologue, is involved in cell envelope biogénesis, cell división and virulence. Scientific reports, 9: 2158 (2019). (* BMG y RRV contribuyeron equitativamente).

Davies-Sala C, Jani S, Zorreguieta A, Tolmasky ME.Identification of the Acinetobacter baumannii Ribonuclease P Catalytic Subunit: Cleavage of a Target mRNA in the Presence of an External Guide Sequence. Front Microbiol. 2018 Oct 8;9:2408. Pubmed

Sorroche, F., Bogino P., Russo D.M., Zorreguieta A., Nievas F., Morales G., Hirsh Ann and Giordano W. Cell autoaggregation, biofilm formation, and plant attachment in a Sinorhizobium meliloti lpsB mutant. Molecular Plant-Microbe Interactions, 31 (10): 1075-1082 (Oct 2018).

Draghi WO, Degrossi J, Bialer M, Brelles-Mariño G, Abdian P, Soler-Bistué A, Wall L, Zorreguieta A. Biodiversity of cultivable Burkholderia species in Argentinean soils under no-till agricultural practices. PLoS One. 2018 Jul 12;13(7). Pubmed

Jani S, Jackson A, Davies-Sala C, Chiem K, Soler-Bistué A, Zorreguieta A, Tolmasky ME. Assessment of External Guide Sequences' (EGS) Efficiency as Inducers of RNase P-Mediated Cleavage of mRNA Target Molecules. Methods Mol Biol. 2018;1737:89-98. Pubmed

Martina P, Leguizamon M, Prieto CI, Sousa SA, Montanaro P, Draghi WO, Stämmler M, Bettiol M, de Carvalho CCCR, Palau J, Figoli C, Alvarez F, Benetti S, Lejona S, Vescina C, Ferreras J, Lasch P, Lagares A, Zorreguieta A, Leitão JH, Yantorno OM, Bosch A. Burkholderia puraquae sp. nov., a novel species of the Burkholderia cepacia complex isolated from hospital settings and agricultural soils. Int J Syst Evol Microbiol. 2018 Jan;68(1):14-20. Pubmed

Kleinman CL, Sycz G, Bonomi HR, Rodríguez RM, Zorreguieta A, Sieira R. ChIP-seq analysis of the LuxR-type regulator VjbR reveals novel insights into the Brucella virulence gene expression network. Nucleic Acids Res. 2017 Jun 2;45(10):5757-5769. Pubmed

Sieira R, Bialer MG, Roset MS, Ruiz-Ranwez V, Langer T, Arocena GM, Mancini E, Zorreguieta A. Combinatorial control of adhesion of Brucella abortus 2308 to host cells by transcriptional rewiring of the trimeric autotransporter btaE gene. Mol Microbiol. 2017 Feb;103(3):553-565.

Vozza, N.F. (*), Abdián, P.L.(*), Russo D.M., Mongiardini, E., Lodeiro, A., Molin, S. Zorreguieta, A. A rhizobial CHDL- (cadherin-like-) lectin participates in assembly and remodeling of the biofilm matrix. Frontiers in Microbiology 7: 1608. eCollection 2016 (2016 Oct 13) (* VNF y APL contribuyeron equitativamente).

Jackson A, Jani S, Sala CD, Soler-Bistué AJ, Zorreguieta A, Tolmasky ME. Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes. Biol Methods Protoc. 2016 Mar;1(1). Pubmed

Fox A, Soto G, Valverde C, Russo D.M, Lagares, A. Zorreguieta A, Alleva, K., Pascuan, C., Mercado-Blanco, J; Dixon, R, Ayub N. “Major cereal crops benefit from biological nitrogen fixation when inoculated with the recombinant nitrogen-fixing bacterium Pseudomonas protegens Pf-5 X940”. Environmental Microbiology, 18 (10) 3522-3534 (2016)

Draghi WO, Mancini Villagra UM, Wall LG, Zorreguieta A. Draft Genome Sequence of Burkholderia cordobensis Type Strain LMG 27620, Isolated from Agricultural Soils in Argentina. Genome Announc. 2015 Oct 22;3(5): e01238-15.

Davies-Sala C, Soler-Bistué A, Bonomo RA, Zorreguieta A, Tolmasky ME. External guide sequence technology: a path to development of novel antimicrobial therapeutics. Ann N Y Acad Sci. 2015 Sep;1354:98-110. Pubmed

Russo DM, Abdian PL, Posadas DM, Williams A, Vozza N, Giordano W, Kannenberg E, Downie JA, Zorreguieta A. Lipopolysaccharide O-chain core region required for cellular cohesion and compaction of in vitro and root biofilms developed by Rhizobium leguminosarum. Appl Environ Microbiol. 2015 Feb;81(3):1013-23.

Draghi WO, Peeters C, Cnockaert M, Snauwaert C, Wall LG, Zorreguieta A, Vandamme P. Burkholderia cordobensis sp. nov., from agricultural soils. Int J Syst Evol Microbiol. 2014 Jun;64(Pt 6):2003-8.

Van der Henst C, de Barsy M, Zorreguieta A, Letesson JJ, De Bolle X. The Brucella pathogens are polarized bacteria. Microbes Infect. 2013 Dec;15(14-15):998-1004. Pubmed

Ruiz-Ranwez V, Posadas DM, Estein SM, Abdian PL, Martin FA, Zorreguieta A. The BtaF Trimeric Autotransporter of Brucella suis Is Involved in Attachment to Various Surfaces, Resistance to Serum and Virulence. PLoS One. 2013 Nov 13;8(11):e79770.

García Angulo VA, Bonomi HR, Posadas DM, Serer MI, Torres AG, Zorreguieta A, Goldbaum FA. Identification and characterization of RibN, a novel family of riboflavin transporters from Rhizobium leguminosarum and other proteobacteria. J Bacteriol. 2013 Oct;195(20):4611-9. Pubmed

Andres P, Lucero C, Soler-Bistué A, Guerriero L, Albornoz E, Tran T, Zorreguieta A, Galas M, Corso A, Tolmasky ME, Petroni A; PMQR-GroupDifferential Distribution of Plasmid Mediated Quinolone Resistance Genes in Clinical Enterobacteria with Unusual Phenotypes of Quinolone Susceptibility from Argentina. Antimicrob Agents Chemother. 2013 Mar 11. Pubmed

Ruiz-Ranwez V, Posadas DM, Van der Henst C, Estein SM, Arocena GM, Abdian PL, Martín FA, Sieira R, De Bolle X, and Zorreguieta A. BtaE, an Adhesin That Belongs to the Trimeric Autotransporter Family, Is Required for Full Virulence and Defines a Specific Adhesive Pole of Brucella suis. Infect Immun. 2013 81:996-1007. Pubmed

Abdian PL, Caramelo JJ, Ausmees N, and Zorreguieta A. RapA2 is a calcium-binding lectin composed of two highly conserved cadherin-like domains that specifically recognize Rhizobium leguminosarum acidic exopolysaccharides. J Biol Chem. 2013; 288:2893-904. Pubmed

Angeles Zorreguieta
Head of Laboratory -

Rodrigo Sieira
Independent Researcher - CONICET

Daniela Marta Russo
Assistant Investigator CONICET

Magalí Bialer
PhD Fellow - CONICET

Lila Ramis

Julián Tarsitano

Gaston Amato
PhD Fellow - CONICET