NHBA is processed by kallikrein from human saliva

Area of Science:

• Microbiology and Immunology
• Protease biochemistry
• Host-pathogen interactions

Background:

• Neisserial Heparin Binding Antigen (NHBA) is a surface protein of Neisseria meningitidis and a target in the Bexsero vaccine.
• NHBA's Arg-rich region binds host proteoglycans, suggesting a role in N. meningitidis colonization.
• NHBA is susceptible to cleavage by bacterial (NalP) and host (hLF) proteases.

Purpose of the Study:

• To investigate NHBA susceptibility to human proteases in saliva.
• To identify the specific salivary protease responsible for NHBA cleavage.
• To understand the implications of NHBA cleavage in Neisseria meningitidis nasopharyngeal colonization.

Main Methods:

• Proteolytic cleavage assays using purified NHBA and human saliva.
• Identification of the responsible protease via enzymatic activity and protein identification techniques.
• Characterization of the NHBA cleavage site using recombinant and native bacterial protein.

Main Results:

• Human saliva effectively cleaves NHBA.
• Human kallikrein 1 (hK1), a salivary serine protease, was identified as the primary enzyme responsible for NHBA cleavage.
• The specific cleavage site on NHBA was identified for both recombinant and native forms.

Conclusions:

• NHBA is a target of host proteases present in saliva, specifically hK1.
• Proteolytic cleavage of NHBA by hK1 may play a role in modulating Neisseria meningitidis colonization.
• Kallikrein represents a potential host defense mechanism against meningococcal infection in the nasopharynx.