A monoclonal antibody directed against a Candida albicans cell wall mannoprotein exerts three anti-C. albicans activities.
Antibodies are believed to play a role in the protection against Candida albicans infections by a number of mechanisms, including the inhibition of adhesion or germ tube formation, opsonization, neutralization of virulence-related enzymes, and direct candidacidal activity. Although some of these biological activities have been demonstrated individually in monoclonal antibodies (MAbs), it is not clear if all these anti-C. albicans activities can be displayed by a single antibody. In this report, we characterized a monoclonal antibody raised against the main target of salivary secretory immunoglobulin A in the cell wall of C. albicans, which exerts three anti-C. albicans activities: (i) inhibition of adherence to HEp-2 cells, (ii) inhibition of germination, and (iii) direct candidacidal activity. MAb C7 reacted with a proteinic epitope from a mannoprotein with a molecular mass of >200 kDa predominantly expressed on the C. albicans germ tube cell wall surface as well as with a number of antigens from Candida lusitaniae, Cryptococcus neoformans, Aspergillus fumigatus, and Scedosporium prolificans. MAb C7 caused a 31.1% inhibition in the adhesion of C. albicans to HEp-2 monolayers and a 55.3% inhibition in the adhesion of C. albicans to buccal epithelial cells, produced a 38.5% decrease in the filamentation of C. albicans, and exhibited a potent fungicidal effect against C. albicans, C. lusitaniae, Cryptococcus neoformans, A. fumigatus, and S. prolificans, showing reductions in fungal growth ranging from 34.2 to 88.7%. The fungicidal activity showed by MAb C7 seems to be related to that reported by antibodies mimicking the activity of a killer toxin produced by the yeast Pichia anomala, since one of these MAbs also reacted with the C. albicans mannoprotein with a molecular mass of >200 kDa. Results presented in this study support the concept of a family of microbicidal antibodies that could be useful in the treatment of a wide range of microbial infections when used alone or in combination with current antimicrobial agents.
Moragues
María D
MD
Departamento de Enfermería I, Universidad del País Vasco, E-48080 Bilbao, Vizcaya, Spain.
Omaetxebarria
Miren J
MJ
Elguezabal
Natalia
N
Sevilla
María J
MJ
Conti
Stefania
S
Polonelli
Luciano
L
Pontón
José
J
D000818:Animals; D000908:Antibodies, Fungal / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D000946:Antigens, Fungal; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D002473:Cell Wall / Q000276:immunology; D005656:Fungal Proteins / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C025363:mannoproteins