Antibodies to Coagulase of Staphylococcus aureus crossreact to Efb and reveal different binding of shared Fibrinogen binding repeats Institutional Repository Document uri icon

abstract

  • AbstractStaphylococcus aureus pathology is caused by a plethora of virulence factors able to combat multiple host defence mechanisms. Fibrinogen (Fg), a critical component in the host coagulation cascade, plays an important role in the pathogenesis of this bacterium, as it is the target of multiple staphylococcal virulence proteins. Amongst its secreted virulence factors, Coagulase (Coa) and Extracellular fibrinogen-binding protein (Efb) share common Fg binding motives and have been described to form a Fg shield around staphylococcal cells, thereby allowing efficient bacterial spreading, phagocytosis escape and evasion of host immune system responses. Targeting these proteins with monoclonal antibodies thus represents a new therapeutic option against S. aureus. To this end, here we report the selection and characterization of fully human, sequence-defined, monoclonal antibodies selected against the C-terminus of Coagulase. Given the functional homology between Coa and Efb, we also investigated if the generated antibodies bound the two virulence factors. Thirteen unique antibodies were isolated from nave antibodies gene libraries by antibody phage display. As anticipated, most of the selected antibodies showed cross-recognition of these two proteins and among them, four were able to block the interaction between Coa/Efb and Fg. Furthermore, our monoclonal antibodies could interact with the two main Fg binding repeats present at the C-terminus of Coa and distinguish them, suggesting the presence of two functionally different Fg-binding epitopes.ImportanceThe death toll related to methicillin-resistant S. aureus piled to almost 1 million people in only one year (2019), ascribing S. aureus to the second leading cause of deaths associated with antimicrobial resistance. Therefore, new therapeutic strategies must be investigated. Blocking the adhesion step with the use of monoclonal antibodies is one promising alternative and Fg is a central plasma protein involved in staphylococcal infection. We present here a panel of monoclonal antibodies raised against Coa, cross-reacting to Efb and targeting the shared Fg binding repeats of Coa. In addition, we describe new epitope determinants in the repeated region of Coa, highlighted by differential binding of the newly selected antibodies.

altmetric score

  • 0.75

author list (cited authors)

  • Bertoglio, F., Ko, Y., Thomas, S., Giordano, L., Scommegna, F. R., Meier, D., ... Visai, L.

citation count

  • 0

complete list of authors

  • Bertoglio, Federico||Ko, Ya-Ping||Thomas, Sheila||Giordano, Liliana||Scommegna, Francesca Romana||Meier, Doris||Polten, Saskia Helmsig||Becker, Marlies||Arora, Srishtee||Hust, Michael||Höök, Magnus||Visai, Livia

Book Title

  • bioRxiv

publication date

  • April 2022