RESUMO
The earliest step in microbial infection is adherence by specific microbial adhesins to the mucosa of the oro-intestinal, nasorespiratory, or genitourinary tract. We inhibited binding of a cell surface adhesin of Streptococcus mutans to salivary receptors in vitro, as measured by surface plasmon resonance, using a synthetic peptide (p1025) corresponding to residues 1025-1044 of the adhesin. Two residues within p1025 that contribute to binding (Q1025, E1037) were identified by site-directed mutagenesis. In an in vivo human streptococcal adhesion model, direct application of p1025 to the teeth prevented recolonization of S. mutans but not Actinomyces, as compared with a control peptide or saline. This novel antimicrobial strategy, applying competitive peptide inhibitors of adhesion, may be used against other microorganisms in which adhesins mediate colonization of mucosal surfaces.
Assuntos
Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Cariostáticos/uso terapêutico , Glicoproteínas de Membrana , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Dente/microbiologia , Actinomyces/efeitos dos fármacos , Actinomyces/isolamento & purificação , Administração Tópica , Sequência de Aminoácidos , Antibacterianos/uso terapêutico , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Cariostáticos/farmacologia , Cárie Dentária/microbiologia , Cárie Dentária/prevenção & controle , Placa Dentária/microbiologia , Epitopos/metabolismo , Humanos , Soros Imunes/análise , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Peptídeos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Infecções Estreptocócicas/prevenção & controle , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia , Dente/efeitos dos fármacosRESUMO
A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgG antibody.The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure. In the human oral cavity, the secretory antibody survived for up to three days, compared with one day for the IgG antibody. The plant secretory antibody afforded specific protection in humans against oral streptococcal colonization for at least four months. We demonstrate that transgenic plants can be used to produce high affinity, monoclonal secretory antibodies that can prevent specific microbial colonization in humans. These findings could be extended to the immunotherapeutic prevention of other mucosal infections in humans and animals.
