Biofilm-associated accumulation-associated protein (Aap): A contributing factor to the predominant growth of Staphylococcus epidermidis in platelet concentrates

Vox Sanguinis ◽  
2018 ◽  
Vol 114 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Meshari Alabdullatif ◽  
Sandra Ramirez-Arcos
Keyword(s):  
Staphylococcus Epidermidis ◽  
Platelet Concentrates ◽  
Accumulation Associated Protein

scholarly journals A Single B-Repeat of Staphylococcus epidermidis Accumulation-Associated Protein Induces Protective Immune Responses in an Experimental Biomaterial-Associated Infection Mouse Model

2014 ◽  
Vol 21 (9) ◽  
pp. 1206-1214 ◽  
Author(s):  
Lin Yan ◽  
Lei Zhang ◽  
Hongyan Ma ◽  
David Chiu ◽  
James D. Bryers
Keyword(s):  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Porous Scaffold ◽  
The United States ◽  
Protein Vaccine ◽  
Weight Changes ◽  
Biofilm Inhibition ◽  
Content Type ◽  
Accumulation Associated Protein

ABSTRACTNosocomial infections are the fourth leading cause of morbidity and mortality in the United States, resulting in 2 million infections and ∼100,000 deaths each year. More than 60% of these infections are associated with some type of biomedical device.Staphylococcus epidermidisis a commensal bacterium of the human skin and is the most common nosocomial pathogen infecting implanted medical devices, especially those in the cardiovasculature.S. epidermidisantibiotic resistance and biofilm formation on inert surfaces make these infections hard to treat. Accumulation-associated protein (Aap), a cell wall-anchored protein ofS. epidermidis, is considered one of the most important proteins involved in the formation ofS. epidermidisbiofilm. A small recombinant protein vaccine comprising a single B-repeat domain (Brpt1.0) ofS. epidermidisRP62A Aap was developed, and the vaccine's efficacy was evaluatedin vitrowith a biofilm inhibition assay andin vivoin a murine model of biomaterial-associated infection. A high IgG antibody response againstS. epidermidisRP62A was detected in the sera of the mice after two subcutaneous immunizations with Brpt1.0 coadministered with Freund's adjuvant. Sera from Brpt1.0-immunized mice inhibitedin vitroS. epidermidisRP62A biofilm formation in a dose-dependent pattern. After receiving two immunizations, each mouse was surgically implanted with a porous scaffold disk containing 5 × 106CFU ofS. epidermidisRP62A. Weight changes, inflammatory markers, and histological assay results after challenge withS. epidermidisindicated that the mice immunized with Brpt1.0 exhibited significantly higher resistance toS. epidermidisRP62A implant infection than the control mice. Day 8 postchallenge, there was a significantly lower number of bacteria in scaffold sections and surrounding tissues and a lower residual inflammatory response to the infected scaffold disks for the Brpt1.0-immunized mice than for of the ovalbumin (Ova)-immunized mice.

scholarly journals The staphylococcal biofilm protein Aap forms a tetrameric species as a necessary intermediate before amyloidogenesis

2020 ◽  
Vol 295 (37) ◽  
pp. 12840-12850
Author(s):  
Alexander E. Yarawsky ◽  
Andrew B. Herr
Keyword(s):  
Staphylococcus Epidermidis ◽  
Analytical Ultracentrifugation ◽  
Conformational Transition ◽  
Mechanistic Model ◽  
Critical Factor ◽  
Equilibrium Studies ◽  
Dimer Interface ◽  
Biologically Relevant ◽  
Accumulation Associated Protein ◽  
Initial Assembly

The accumulation-associated protein (Aap) from Staphylococcus epidermidis is a biofilm-related protein that was found to be a critical factor for infection using a rat catheter model. The B-repeat superdomain of Aap, composed of 5–17 B-repeats, each containing a Zn2+-binding G5 and a spacer subdomain, is responsible for Zn2+-dependent assembly leading to accumulation of bacteria during biofilm formation. We previously demonstrated that a minimal B-repeat construct (Brpt1.5) forms an antiparallel dimer in the presence of 2–3 Zn2+ ions. More recently, we have reported the presence of functional amyloid-like fibrils composed of Aap within S. epidermidis biofilms and demonstrated that a biologically relevant construct containing five and a half B-repeats (Brpt5.5) forms amyloid-like fibrils similar to those observed in the biofilm. In this study, we analyze the initial assembly events of the Brpt5.5 construct. Analytical ultracentrifugation was utilized to determine hydrodynamic parameters of reversibly associating species and to perform linked equilibrium studies. Linkage studies indicated a mechanism of Zn2+-induced dimerization similar to smaller constructs; however, Brpt5.5 dimers could then undergo further Zn2+-induced assembly into a previously uncharacterized tetramer. This led us to search for potential Zn2+-binding sites outside of the dimer interface. We developed a Brpt5.5 mutant that was unable to form the tetramer and was concordantly incapable of amyloidogenesis. CD and dynamic light scattering indicate that a conformational transition in the tetramer species is a critical step preceding amyloidogenesis. This mechanistic model for B-repeat assembly and amyloidogenesis provides new avenues for potential therapeutic targeting of staphylococcal biofilms.

scholarly journals Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

2014 ◽  
Vol 83 (1) ◽  
pp. 214-226 ◽  
Author(s):  
Carolyn R. Schaeffer ◽  
Keith M. Woods ◽  
G. Matt Longo ◽  
Megan R. Kiedrowski ◽  
Alexandra E. Paharik ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Host Cells ◽  
Content Type ◽  
Microtiter Plates ◽  
Allelic Replacement ◽  
Abiotic Surfaces ◽  
Cell Accumulation ◽  
Accumulation Associated Protein

Biofilm formation is the primary virulence factor ofStaphylococcus epidermidis.S. epidermidisbiofilms preferentially form on abiotic surfaces and may contain multiple matrix components, including proteins such as accumulation-associated protein (Aap). Following proteolytic cleavage of the A domain, which has been shown to enhance binding to host cells, B domain homotypic interactions support cell accumulation and biofilm formation. To further define the contribution of Aap to biofilm formation and infection, we constructed anaapallelic replacement mutant and anicaADBC aapdouble mutant. When subjected to fluid shear, strains deficient in Aap production produced significantly less biofilm than Aap-positive strains. To examine thein vivorelevance of our findings, we modified our previously described rat jugular catheter model and validated the importance of immunosuppression and the presence of a foreign body to the establishment of infection. The use of our allelic replacement mutants in the model revealed a significant decrease in bacterial recovery from the catheter and the blood in the absence of Aap, regardless of the production of polysaccharide intercellular adhesin (PIA), a well-characterized, robust matrix molecule. Complementation of theaapmutant with full-length Aap (containing the A domain), but not the B domain alone, increased initial attachment to microtiter plates, as did intransexpression of the A domain in adhesion-deficientStaphylococcus carnosus. These results demonstrate Aap contributes toS. epidermidisinfection, which may in part be due to A domain-mediated attachment to abiotic surfaces.

scholarly journals The Terminal A Domain of the Fibrillar Accumulation-Associated Protein (Aap) of Staphylococcus epidermidis Mediates Adhesion to Human Corneocytes

2009 ◽  
Vol 191 (22) ◽  
pp. 7007-7016 ◽  
Author(s):  
Robin L. Macintosh ◽  
Jane L. Brittan ◽  
Ritwika Bhattacharya ◽  
Howard F. Jenkinson ◽  
Jeremy Derrick ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Domain Architecture ◽  
Opportunistic Pathogen ◽  
Additional Function ◽  
Artificial Joints ◽  
A Cell ◽  
Skin Colonization ◽  
Accumulation Associated Protein

ABSTRACT The opportunistic pathogen Staphylococcus epidermidis colonizes indwelling medical devices by biofilm formation but is primarily a skin resident. In many S. epidermidis strains biofilm formation is mediated by a cell wall-anchored protein, the accumulation-associated protein (Aap). Here, we investigate the role of Aap in skin adhesion. Aap is an LPXTG protein with a domain architecture including a terminal A domain and a B-repeat region. S. epidermidis NCTC 11047 expresses Aap as localized, lateral tufts of fibrils on one subpopulation of cells (Fib+), whereas a second subpopulation does not express these fibrils of Aap (Fib−). Flow cytometry showed that 72% of NCTC 11047 cells expressed Aap and that 28% of cells did not. Aap is involved in the adhesion of Fib+ cells to squamous epithelial cells from the hand (corneocytes), as the recombinant A-domain protein partially blocked binding to corneocytes. To confirm the role of the Aap A domain in corneocyte attachment, Aap was expressed on the surface of Lactococcus lactis MG1363 as sparsely distributed, peritrichous fibrils. The expression of Aap increased corneocyte adhesion 20-fold compared to L. lactis carrying Aap without an A domain. S. epidermidis isolates from catheters, artificial joints, skin, and the nose also used the A domain of Aap to adhere to corneocytes, emphasizing the role of Aap in skin adhesion. In addition, L. lactis expressing Aap with different numbers of B repeats revealed a positive correlation between the number of B repeats and adhesion to corneocytes, suggesting an additional function for the B region in enhancing A-domain-dependent attachment to skin. Therefore, in addition to its established role in biofilm formation, Aap can also promote adhesion to corneocytes and is likely to be an important adhesin in S. epidermidis skin colonization.

scholarly journals Comparative characterisation of the biofilm-production abilities of Staphylococcus epidermidis isolated from human skin and platelet concentrates

2018 ◽  
Vol 67 (2) ◽  
pp. 190-197 ◽  
Author(s):  
Mariam Taha ◽  
Carissa Kohnen ◽  
Shruti Mallya ◽  
Yuntong Kou ◽  
Adriana Zapata ◽  
...  
Keyword(s):  
Human Skin ◽  
Staphylococcus Epidermidis ◽  
Platelet Concentrates ◽  
Biofilm Production

scholarly journals Staphylococcus epidermidis Forms Floating Micro-colonies in Platelet Concentrates at the Early Stage of Contamination

2009 ◽  
Vol 55 (5) ◽  
pp. 726-731 ◽  
Author(s):  
Yasuo Motoyama ◽  
Nobuyasu Yamaguchi ◽  
Mami Matsumoto ◽  
Tomoaki Ichijo ◽  
Hideto Nagumo ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Early Stage ◽  
Platelet Concentrates

scholarly journals Phenotypic and Genetic Analysis of Biofilm Formation by Staphylococcus epidermidis

Medicina ◽  
2012 ◽  
Vol 48 (6) ◽  
pp. 45 ◽  
Author(s):  
Iveta Līduma ◽  
Tatjana Tračevska ◽  
Uģis Bērs ◽  
Aija Žileviča
Keyword(s):  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Microtiter Plate ◽  
Clinical Isolates ◽  
Control Group ◽  
Clinical Group ◽  
Clinical Strains ◽  
Implanted Medical Devices ◽  
Important Virulence Factor ◽  
Accumulation Associated Protein

Objective. The most important virulence factor of Staphylococcus epidermidis is their capability to form a biofilm on the surfaces of implanted medical devices. The accumulative phase of biofilm formation is linked to the production of intercellular adhesin encoded by the icaADBC operon and accumulation-associated protein by the aap gene. The aim of the study was to investigate biofilm formation phenotypically and genetically in clinical strains of S. epidermidis in comparison with commensal strains. Material and Methods. The study was carried out in 4 hospitals in Riga, Latvia. In total, 105 clinical strains of Staphylococcus epidermidis isolated from patients’ blood (n=67) and intravenous catheters (n=38) in a case of laboratory-confirmed bacteremia were studied. Moreover, 60 Staphylococcus epidermidis commensal strains isolated from nose epithelium of healthy people were included as a control group. Appearance of the icaA and aap genes was tested by polymerase chain reaction. The microtiter plate method was used. Results. Biofilm formation was detected in 50 (47%) of Staphylococcus epidermidis isolates in the clinical group and 15 (25%) of isolates in the control group (P=0.0049). Among 50 biofilmforming clinical isolates, 46 (92%) were positive for the icaA and/or aap genes. The icaA and aap genes were not found only in 4 strains. Conclusions. The clinical isolates of Staphylococcus epidermidis were more likely to form biofilms than the commensal strains. The carriage of the icaA or aap gene alone, or their absence, is not applicable as a molecular marker for the discrimination invasive Staphylococcus epidermidis strains from contaminants.

scholarly journals Role for the A Domain of Unprocessed Accumulation-Associated Protein (Aap) in the Attachment Phase of the Staphylococcus epidermidis Biofilm Phenotype

2014 ◽  
Vol 196 (24) ◽  
pp. 4268-4275 ◽  
Author(s):  
B. P. Conlon ◽  
J. A. Geoghegan ◽  
E. M. Waters ◽  
H. McCarthy ◽  
S. E. Rowe ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Accumulation Associated Protein
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