Molecular basis of bacterial lectin recognition of eukaryotic glycans: The case of Mycoplasma pneumoniae and Mycoplasma genitalium cytoadhesins.

Autor: Marseglia A; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy., Forgione MC; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy., Marcos-Silva M; Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain., Di Carluccio C; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy., Manabe Y; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan., Vizarraga D; Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Parc Científic de Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain., Nieto-Fabregat F; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy., Lenza MP; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy; Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49 - 80131 Napoli Italy., Fukase K; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan., Molinaro A; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan., Pich OQ; Departament de Bioquímica i Biologia Molecular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; Laboratori de Recerca en Microbiologia i Malalties Infeccioses, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), UniversitatAutònoma de Barcelona, Sabadell, Spain., Aparicio D; Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Parc Científic de Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain., Silipo A; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy; Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan., Marchetti R; Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126 Napoli, Italy. Electronic address: roberta.marchetti@unina.it.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 279 (Pt 2), pp. 135277. Date of Electronic Publication: 2024 Sep 01.
DOI: 10.1016/j.ijbiomac.2024.135277
Abstrakt: Mycoplasma pneumoniae and Mycoplasma genitalium are two emerging bacterial pathogens that colonize the human respiratory and urogenital epithelia, respectively. Both pathogens express cell surface cytoadhesins that play a crucial role in the interaction with the host, mediating the attachment to sialylated glycan receptors and triggering infection. The design of competitive binding inhibitors of Mycoplasma cytoadhesins has potential to disrupt these interactions and lessen bacterial pathogenesis. To this end, we report here molecular insights into the adhesion mechanisms of M. pneumoniae and M. genitalium, which are largely mediated by sialylated glycans on the host cell surface. In detail, a combination of Nuclear Magnetic Resonance (NMR) spectroscopy, fluorescence analysis and computational studies allowed us to explore the recognition by the cytoadhesins P40/P90 in M. pneumoniae and P110 in M. genitalium of sialylated N- and O-glycans. We reveal that, unlike other bacterial adhesins, which are characterized by a wide binding pocket, Mycoplasma cytoadhesins principally accommodate the sialic acid residue, in a similar manner to mammalian Siglecs. These findings represent crucial insight into the future development of novel compounds to counteract Mycoplasma infections by inhibiting bacterial adherence to host tissues.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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