Immunobiology of Methicillin-Resistant <i>Staphylococcus aureus</i>: Immune Response of Rabbits and Patients to Systemic Infection

Abstract

Teichoic acid (TA) and peptidoglycan (PG) extracted from Staphylococcus aureus strains ATCC 25923 and Lafferty as well as formalinized cells of these two strains and several clinical methicillin-resistant S. aureus (MRSA) isolates were immunogenic for New Zealand White rabbits. Rabbits which had recovered from experimental bacteremia due to MRSA seroconverted, i.e. demonstrated raised titers of antibodies against TA and PG of the S. aureus strain Lafferty and against whole cells (WC) and ultrasound cell lysates (UCL) of MRSA isolates No. 1 and 2 (representative of nosocomial MRSA strain I), as determind with enzyme-linked immunosorbent assays. Furthermore, sera from 2 long-term survivor rabbits recognized four polypeptides (apparent molecular weights = 38.9, 33.9, 30.9, and 28.2 kDa) shared by UCL extracts from MRSA isolates No. 1 and 2, as determined with immunoblots. Neither normal nor immune rabbit sera augmented the bactericidal activity of fresh defibrinated human blood (65% v/v) against selected MRSA isolates and S. aureus strain ATCC 25923. Sera from 12 patients with documented systemic infection due to MRSA outbreak strain I were examined for IgM and IgG antibodies against TA, WC, and UCL antigens. Three patient sera exhibited raised IgM antibodies against TA; 7 of 12 patient sera showed increased IgG anti-TA titers. Only 1 patient had a markedly raised IgM anti-WC titer, whereas 4 and 10 of the patients had increased IgG titers against WC from MRSA isolates No. 1 and 2, respectively. However, all 12 patients had raised IgG titers against UCL from MRSA isolate No. 2 versus 4 of 12 patients with elevated IgG titers against UCL from MRSA isolate No. 1. Immunoblots with 3 selected patient sera revealed IgG antibodies to be more multifaceted than IgM antibodies. Sera from 11 of the 12 patients contained antimicrobial drug(s); yet only 5 of these 11 sera (used at 10% v/v in broth) killed inocula of MRSA isolate No. 43. None of the 12 patient sera (10% v/v) enhanced the bactericidal activity of human blood against selected MRSA isolates. Neither three commercial intravenously applicable IgG preparations nor an IgG anti-α-hemolysin formulation (employed at 10% v/v) augmented the bactericidal activity of fresh defibrinated human blood against selected MRSA isolates comprising MRSA outbreak strain I.

Towards the immune proteome of Staphylococcus aureus – The anti-S. aureus antibody response

“…As expected, antibodies against whole cells were frequently observed in different patient cohorts (endocarditis, septicemia) (Hershman et al, 1989;Jarlov et al, 1985;Ryding et al, 1992;Traub et al, 1996). However, protein A, which is highly conserved in S. aureus and avidly binds to human IgG, frequently caused false-positive results (Hershman et al, 1989;Jarlov et al, 1985).…”

“…It has been estimated that 60-85% of all IgG-binding to an S. aureus cell lysate was due to anti-LTA antibodies (Dryla et al, 2005). Most patients with S. aureus infection have increased concentrations of anti-TA antibodies (Kumar et al, 2005;Traub et al, 1996).…”

Human antibody response during sepsis against targets expressed by methicillin resistant Staphylococcus aureus

“…Similar ¢ndings have been described before. However, the antigens were not analyzed in detail [33,38]. IsaA speci¢c antibodies were detected in all healthy adults, in all colonized patients as well as in patients su¡ering from sepsis.…”

Identification of an Immunodominant ABC Transporter in Methicillin-Resistant Staphylococcus aureus Infections

“…Previous studies have shown a complex picture with humoral responses demonstrated against exotoxins, exoenzymes, cell wall components such as peptidoglycan and teichoic acid, and capsules (5,42).…”