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

• Published in: International journal of biological macromolecules 2024-11, Vol.279 (Pt 2), p.135277, Article 135277
• Main Authors: Marseglia, Angela, Forgione, Maria Concetta, Marcos-Silva, Marina, Di Carluccio, Cristina, Manabe, Yoshiyuki, Vizarraga, David, Nieto-Fabregat, Ferran, Lenza, Maria Pia, Fukase, Koichi, Molinaro, Antonio, Pich, Oscar Q., Aparicio, David, Silipo, Alba, Marchetti, Roberta
• Format: Article
• Language: English
• Subjects: Bacterial lectins; Molecular recognition; Sialoglycans; STD NMR
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135277

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. [Display omitted] •We investigated the binding of host sialylated glycans to mycoplasma cytoadhesins•The structural and conformational features required for the recognition were revealed•The 3D models of protein-ligand complexes were depicted