Heat-inducible ATP-binding proteins of Candida albicans are recognized by sera of infected patients

Abstract

Four proteins from Candida albicans extracts have been isolated by ATP affinity chromatography. These proteins were found to be at elevated levels in extracts of cells raised from 25 "C to 37 "C, but were present at low levels in cells grown at 25 "C. The molecular masses of the proteins (38-42 kDa, 66-68 kDa, 70-72 kDa and 74-76 kDa) correspond to the published sizes of C. albicans heat-shock proteins. Three of the four proteins were recognized by the sera of patients with oral and/or oesophageal C. albicans infections, with the 70-72 kDa protein reacting in all cases tested. Binding of antibodies to two of the other proteins (38-42 kDa and 74-76 kDa) differed from patient to patient. IgA antibodies were the dominant immunoglobulin class in these mucosal C. albicans infections. The IgA antibody titre may be of diagnostic value and seemed to be correlated to the severity of infections, with a higher level in oesophageal infections compared to oral infections. Antibody binding to these proteins was specific as the sera did not show the same enhanced recognition with bacterial or HeLa cell heat-shock proteins.

Expression of virulence factors inCandida albicans

“…In addition, antibody responses have been detected to various glycolytic enzymes (40), especially enolase, and heat shock proteins (Hsp's; Ref. 39), most notably a fragment of Hsp90 (see Refs. 6 and 7).…”

Modelling the Regulation of Thermal Adaptation in Candida albicans, a Major Fungal Pathogen of Humans

“…Fourth, C. albicans heat shock proteins are immunogenic, thereby directly affecting host-pathogen interactions during infection [23], [24]. Finally, autoantibodies against Hsp90 are immunoprotective against C. albicans infections [25], [26], [27]. Taken together, the heat shock response of fungal pathogens is of fundamental importance because it is essential for virulence [12], and because heat shock proteins represent targets for novel therapeutic strategies [28].…”

Oral Microbial Heat-shock Proteins and Their Potential Contributions to Infections

“…Native A. actinomycetemcomitans GroEL consists of two stacked 22, 26, 27, 30, 31, 38, 41, 42, 15, 25, 27, 37, 51, 58, Koga et al, 1993;Løkensgard actinomycetemcomitans 45, 47, 58, 60, 70, 82, 90 60-64, 70-73, 79, 89-90 et al, 1994;Nakano et al, 1995Bacteroides forsythus 60 Vayssier et al, 1994Candida albicans 18, 26, 34, 54, 72, 76, 81, 85, 98 Zeuthen and Howard, 1989Campylobacter rectus 50, 64, 73, 88 Hinode et al, 1998bFusobacterium nucleatum 54, 65, 78, 80, 28, 30, 32, 62, 70, 92-95 Mayrand et al, 199982, 89, 90, 115 Skar Jayaraman and Burne, 1995;Hrimech et al, 2000;Lemos et al, 2001 a Proteins whose molecular weight is in bold represent the major bands detected by SDS-PAGE following the heat stress. Koga et al, 1993;Vayssier et al, 1994;Kirby et al, 1995;Nakano et al, 1995;Hinode et al, 1996DnaK A,C,D 80 Løkensgard et al, 1994Vayssier et al, 1994;Yoshida et Swoboda et al, 1993;Sepulveda et al, 1996HSP60 E 66-68 Swoboda et al, 1993Sepulveda et al, 1996HSP70 D,E 74-76 Swoboda et al, 1993La Valle et al, 1995;Sepulveda et al, 1996 HSP90 D,E 47 (heat-stable form) Swoboda et al, 1993;Matthews et al, 1995;Sepulveda et al, 1996 Hotokezaka et al, 1994Hotokezaka et al, , 1997…”

“…Antibodies to this protein have been found in the sera of candidiasis and AIDS patients (Chaffin et al, 1998). In addition, sera from patients with oral or esophageal candidiasis react with heatinducible and ATP-binding proteins of C. albicans, which are probably HSPs (Swoboda et al, 1993;Chaffin et al, 1998). Patients with candidiasis have also been shown to have higher titers of IgA directed against mycobacterial GroEL than do healthy subjects (Ivanyi and Wong, 1992;Chaffin et al, 1998).…”