Protection from Staphylococcus aureus mastitis associated with poly-N-acetyl β-1,6 glucosamine specific antibody production using biofilm-embedded bacteria

Abstract

Staphylococcus aureus vaccines based on bacterins surrounded by slime, surface polysaccharides coupled to protein carriers and polysaccharides embedded in liposomes administered together with non-biofilm bacterins confer protection against mastitis. However, it remains unknown whether protective antibodies are directed to slime-associated known exopolysaccharides and could be produced in the absence of bacterin immunizations. Here, a sheep mastitis vaccination study was carried out using bacterins, crude bacterial extracts or a purified exopolysaccharide from biofilm © 2009 Elsevier Ltd. All rights reserved.Corresponding author: Beatriz Amorena, e Instituto de Agrobiotecnología, CSIC-Universidad Pública de Navarra-Gobierno de Navarra, 31192 Mutilva Baja, Spain. Phone: +34 948 16 80 06; Fax: + 34 948 23 21 91; bamorena@unavarra.es. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosed potential conflicts of interestDrs. T. Maira-Litran and G.B. Pier declare they have a financial interest in the form of licensing and consulting income for the commercial development of PNAG-based vaccines and immunotherapies related to issued U.S. patents 7,252,828, 7,015,007, 6,743,431, 6,399,066, 5,980,910, and NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript bacteria delivered in different vehicles. This polysaccharide reacted specifically with antibodies to poly-N-acetyl-β-1,6-glucosamine (PNAG) and not with antibodies to other capsular antigens or bacterial components. Following intra-mammary challenge with biofilm-producing bacteria, antibody production against the polysaccharide, milk bacterial counts and mastitis lesions were determined. Bacterins from strong biofilm-producing bacteria triggered the highest production of antibodies to PNAG and conferred the highest protection against infection and mastitis, compared with weak biofilm-producing bacteria and non-cellular inocula. Thus, bacterins from strong biofilm bacteria, rather than purified polysaccharide, are proposed as a cost-efficient vaccination against S. aureus ruminant mastitis.

Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

“…Numerous approaches have been adopted in order to identify staphylococcal surface-and cell wall-associated proteins as antigenic candidates for a vaccine against S. aureus infections (34,49,51,53,(56)(57)(58)(59)(60). However, few works have been focused on the selection of antigens that could also protect against biofilm-associated bacteria (14,(24)(25)(26). This is particularly important because S. aureus biofilms play a major role in persistent infections formed on the surface of implanted medical devices and in deep tissues.…”

“…Some of these biofilm mediators have already been proposed as vaccine antigens against S. aureus infections. Different studies have shown that administration of deacetylated PNAG conjugated with diphtheria toxin as a carrier protein induces an immunological response that protects against S. aureus infection (14,(24)(25)(26). Furthermore, a recent study by Cywes-Bentley et al showed that PNAG or a structural variant of PNAG is a conserved surface polysaccharide produced by many pathogenic bacteria, fungi, and protozoal parasites and demonstrated that passive immunization with antibodies to PNAG protects mice against both local and systemic infections caused by many of these pathogens (27).…”

Mastitis in sheep – The last 10 years and the future of research

“…More recently, biofilm matrix polysaccharides were used for development of protective immune response against S. aureus mastitis in ewes (Perez et al, 2009). This approach employs cell-free surface polysaccharide in various vehicles, bacterial unbound cells or bacterial cells embedded in their biofilm matrix in various adjuvants.…”

Adaptation of Staphylococcus aureus to the cystic fibrosis lung

“…Low oxygen concentrations like those present in the CF sputa trigger the upregulation of ica transcription (Ulrich et al, 2007) and thus may be one important signal to induce biofilm formation in vivo. Based on these results, PIA/PNAG is now being evaluated as a vaccine candidate to protect against S. aureus infection (McKenney et al, 2000;Perez et al, 2009).…”