title: Monoclonal antibodies against accumulation-associated protein affect EPS biosynthesis and enhance bacterial accumulation of Staphylococcus epidermidis.
abstract: Because there is no effective antibiotic to eradicate Staphylococcus epidermidis biofilm infections that lead to the failure of medical device implantations, the development of anti-biofilm vaccines is necessary. Biofilm formation by S. epidermidis requires accumulation-associated protein (Aap) that contains sequence repeats known as G5 domains, which are responsible for the Zn(2+)-dependent dimerization of Aap to mediate intercellular adhesion. Antibodies against Aap have been reported to inhibit biofilm accumulation. In the present study, three monoclonal antibodies (MAbs) against the Aap C-terminal single B-repeat construct followed by the 79-aa half repeat (AapBrpt1.5) were generated. MAb(18B6) inhibited biofilm formation by S. epidermidis RP62A to 60% of the maximum, while MAb(25C11) and MAb(20B9) enhanced biofilm accumulation. All three MAbs aggregated the planktonic bacteria to form visible cell clusters. Epitope mapping revealed that the epitope of MAb(18B6), which recognizes an identical area within AapBrpt constructs from S. epidermidis RP62A, was not shared by MAb(25C11) and MAb(20B9). Furthermore, all three MAbs were found to affect both Aap expression and extracellular polymeric substance (EPS, including extracellular DNA and PIA) biosynthesis in S. epidermidis and enhance the cell accumulation. These findings contribute to a better understanding of staphylococcal biofilm formation and will help to develop epitope-peptide vaccines against staphylococcal infections.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lou
authors.forename: Xueqin
authors.initials: X
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Renzheng
authors.initials: R
authors.lastname: Huang
authors.forename: Jingran
authors.initials: J
authors.lastname: Liu
authors.forename: Huayong
authors.initials: H
authors.lastname: Liu
authors.forename: Fangyou
authors.initials: F
authors.lastname: Yu
authors.forename: Baixing
authors.initials: B
authors.lastname: Ding
authors.forename: Yalin
authors.initials: Y
authors.lastname: Huang
authors.forename: Wenyan
authors.initials: W
authors.lastname: Tong
authors.forename: Di
authors.initials: D
authors.lastname: Qu
mesh_terms: D018829:Adhesins, Bacterial / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology; D018441:Biofilms; D001704:Biopolymers / Q000096:biosynthesis*; D004269:DNA, Bacterial / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005110:Extracellular Space / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology; D008969:Molecular Sequence Data; D020449:Repetitive Sequences, Amino Acid; D013212:Staphylococcus epidermidis / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D001704:Biopolymers; D004269:DNA, Bacterial; D000939:Epitopes