scholarly journals Staphylococcus aureus vaccines: Deviating from the carol

2016 ◽  
Vol 213 (9) ◽  
pp. 1645-1653 ◽  
Author(s):  
Dominique Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Invasive Disease ◽  
Phagocytic Cells ◽  
Subunit Vaccines ◽  
Clinical Endpoints ◽  
Patients At Risk ◽  
Resistant Strains ◽  
Opsonophagocytic Killing ◽  
Drug Resistant Strains

Staphylococcus aureus, a commensal of the human nasopharynx and skin, also causes invasive disease, most frequently skin and soft tissue infections. Invasive disease caused by drug-resistant strains, designated MRSA (methicillin-resistant S. aureus), is associated with failure of antibiotic therapy and elevated mortality. Here we review polysaccharide-conjugate and subunit vaccines that were designed to prevent S. aureus infection in patients at risk of bacteremia or surgical wound infection but failed to reach their clinical endpoints. We also discuss vaccines with ongoing trials for combinations of polysaccharide-conjugates and subunits. S. aureus colonization and invasive disease are not associated with the development of protective immune responses, which is attributable to a large spectrum of immune evasion factors. Two evasive strategies, assembly of protective fibrin shields via coagulases and protein A–mediated B cell superantigen activity, are discussed as possible vaccine targets. Although correlates for protective immunity are not yet known, opsonophagocytic killing of staphylococci by phagocytic cells offers opportunities to establish such criteria.

scholarly journals Introduction of the mec Element (Methicillin Resistance) into Staphylococcus aureus Alters In Vitro Functional Activities of Fibrinogen and Fibronectin Adhesins

1998 ◽  
Vol 42 (3) ◽  
pp. 564-570 ◽  
Author(s):  
Pierre E. Vaudaux ◽  
Vincenza Monzillo ◽  
Patrice Francois ◽  
Daniel P. Lew ◽  
Tim J. Foster ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Bacterial Colonization ◽  
Protein A ◽  
Methicillin Resistant ◽  
Functional Activities ◽  
Extracellular Matrix Components ◽  
Resistant Strains ◽  
The Impact

ABSTRACT Some methicillin-resistant strains of Staphylococcus aureus are defective in the production of major surface components such as protein A, clumping factor, or other important adhesins to extracellular matrix components which may play a role in bacterial colonization and infection. To evaluate the impact of methicillin resistance (mec) determinants on bacterial adhesion mediated by fibrinogen or fibronectin adhesins, we compared the in vitro attachment of two genetically distinct susceptible strains (NCTC8325 and Newman) to protein-coated surfaces with that of isogenic methicillin-resistant derivatives. All strains containing an intactmec element in their chromosomes were found to be defective in adhesion to fibrinogen and fibronectin immobilized on polymethylmethacrylate coverslips, regardless of the presence or absence of additional mutations in the femA,femB, or femC gene, known to decrease expression of methicillin resistance in S. aureus. Western ligand affinity blotting or immunoblotting of cell wall-associated adhesins revealed similar contents of fibrinogen- or fibronectin-binding proteins in methicillin-resistant strains compared to those of their methicillin-susceptible counterparts. In contrast to methicillin-resistant strains carrying a mec element in their genomes, methicillin-resistant strains constructed in vitro, by introducing the mecA gene on a plasmid, retained their adhesion phenotypes. In conclusion, the chromosomal insertion of themec element into genetically defined strains of S. aureus impairs the in vitro functional activities of fibrinogen or fibronectin adhesins without altering their production. This effect is unrelated to the activity of the mecA gene.

Characterization of Borderline Oxacillin-Resistant Staphylococcus aureus Isolated from Food of Animal Origin

2010 ◽  
Vol 73 (7) ◽  
pp. 1325-1327 ◽  
Author(s):  
JAROSŁAW BYSTROŃ ◽  
MAGDALENA PODKOWIK ◽  
KAMILA KORZEKWA ◽  
ELŻBIETA LIS ◽  
JERZY MOLENDA ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Meca Gene ◽  
Raw Milk ◽  
Animal Origin ◽  
Molecular Characteristics ◽  
Type I ◽  
Staphylococcal Protein A ◽  
Food Of Animal Origin ◽  
Resistant Strains

In this study, the molecular characteristics of food-derived oxacillin-resistant Staphylococcus aureus were determined. Eight borderline oxacillin-resistant strains with MICs of 2 to 4 μg/ml were identified from 132 S. aureus isolates of food origin. One of the two isolates with a MIC of 4 μg/ml was methicillin-resistant determinant (mecA) gene positive, and the other six with MICs of 2 μg/ml were mecA negative. The mecA-positive isolate was classified as sequence type (ST)228, staphylococcal protein A (spa) type t041, and carried the staphylococcal cassette chromosome mec type I element. Two borderline oxacillin-resistant strains were classified as spa t008 and ST8, and the remaining five as spa t164 and ST20. The mecA-positive strain and four borderline oxacillin-resistant strains were found enterotoxigenic. The enterotoxin genes detected in these strains included selp, egc1, and sed-sej-selr. The borderline-resistant S. aureus isolates from a manually handled product, i.e., minced pork, were shown genetically related to strains associated with human infections. This suggests that humans can be considered as a source of contamination of this food with oxacillin-resistant S. aureus strains. The genotypes of the investigated milk borderline-resistant isolates were shown to occur not only in cows, but also in humans. Since manual handling is reduced in raw milk production, a human origin of S. aureus seems unlikely. Because knowledge of the genotypes of animal staphylococci is limited, more research is needed to address the question of the origin of antibiotic-resistant S. aureus strains in food.

scholarly journals Effects of Tormentic Acid and the Extracts from Callistemon citrinus on the Production of Extracellular Proteases by Staphylococcus aureus

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Rumbidzai Mashezha ◽  
Molly Mombeshora ◽  
Stanley Mukanganyama
Keyword(s):  
Staphylococcus Aureus ◽  
Ethanol Extract ◽  
Extracellular Protease ◽  
Protease Production ◽  
Extracellular Proteases ◽  
Therapeutic Molecules ◽  
Antibacterial Susceptibility ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Tormentic Acid

Staphylococcus aureus is among the common nosocomial pathogens. Antibiotics have been used to treat S. aureus infections. However, there has been increased mortality associated with drug-resistant strains of S. aureus. Extracellular proteases have been implicated to be responsible for the transition of S. aureus from an adhesive pathogen to an invasive pathogen. The development of resistant strains has necessitated the search for new sources of drugs. Plants have been traditionally used as sources of therapeutic molecules. The objective of this study was to determine the effect of tormentic acid and the extracts from Callistemon citrinus on the production of extracellular proteases by S. aureus. The broth microdilution antibacterial susceptibility assay was used to determine the antibacterial effects of tormentic acid and the extracts on S. aureus. Both extracts showed a minimum inhibitory concentration (MIC) value of 50 μg/ml. The water : ethanol (50 : 50) and the dichloromethane : methanol (50 : 50) extracts were found to be bactericidal against S. aureus at a concentration of 100 μg/ml and 50 μg/ml, respectively. The effect of tormentic acid and extracts on extracellular protease production was investigated using the protease assay. A zone of proteolytic activity (Pr) was measured as the ratio of the diameter of the colony to the total diameter of colony plus zone of hydrolysis. The extracts reduced the production of extracellular proteases, while tormentic acid completely inhibited the production of extracellular proteases by S. aureus. The Pr value for tormentic acid was found to be 1. The Pr values of the dichloromethane : methanol extract and the water : ethanol extract were 0.92 and 0.84, respectively. In conclusion, tormentic acid was shown to inhibit extracellular protease production; therefore, there is need to explore its use in antivirulence therapy to combat S. aureus infections.

scholarly journals Glycosylation-dependent opsonophagocytic activity of staphylococcal protein A antibodies

2020 ◽  
Vol 117 (37) ◽  
pp. 22992-23000
Author(s):  
Xinhai Chen ◽  
Miaomiao Shi ◽  
Xin Tong ◽  
Hwan Keun Kim ◽  
Lai-Xi Wang ◽  
...  
Keyword(s):  
Bacterial Pathogens ◽  
Human Monoclonal Antibody ◽  
Functional Characterization ◽  
Protein A ◽  
Therapeutic Benefit ◽  
Staphylococcal Protein A ◽  
Staphylococcal Protein ◽  
Clinical Endpoints ◽  
Vaccine Trials ◽  
Opsonophagocytic Killing

Antibodies may bind to bacterial pathogens or their toxins to control infections, and their effector activity is mediated through the recruitment of complement component C1q or the engagement with Fcγ receptors (FcγRs). For bacterial pathogens that rely on a single toxin to cause disease, immunity correlates with toxin neutralization. Most other bacterial pathogens, including Staphylococcus aureus, secrete numerous toxins and evolved multiple mechanisms to escape opsonization and complement killing. Several vaccine candidates targeting defined surface antigens of S. aureus have failed to meet clinical endpoints. It is unclear that such failures can be solely attributed to the poor selection of antibody targets. Thus far, studies to delineate antibody-mediated uptake and killing of Gram-positive pathogens remain extremely limited. Here, we exploit 3F6-hIgG1, a human monoclonal antibody that binds and neutralizes the abundant surface-exposed Staphylococcal protein A (SpA). We find that galactosylation of 3F6-hIgG1 that favors C1q recruitment is indispensable for opsonophagocytic killing of staphylococci and for protection against bloodstream infection in animals. However, the simple removal of fucosyl residues, which results in reduced C1q binding and increased engagement with FcγR, maintains the opsonophagocytic killing and protective attributes of the antibody. We confirm these results by engineering 3F6-hIgG1 variants with biased binding toward C1q or FcγRs. While the therapeutic benefit of monoclonal antibodies against infectious disease agents may be debatable, the functional characterization of such antibodies represents a powerful tool for the development of correlates of protection that may guide future vaccine trials.

scholarly journals ClpC affects the intracellular survival capacity of Staphylococcus aureus in non-professional phagocytic cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gubesh Gunaratnam ◽  
Lorena Tuchscherr ◽  
Mohamed I. Elhawy ◽  
Ralph Bertram ◽  
Janina Eisenbeis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Intracellular Survival ◽  
Host Cells ◽  
Virulence Determinants ◽  
Phagocytic Cells ◽  
Survival Capacity ◽  
Shock Proteins ◽  
Mutant Cells

Abstract Invasion and persistence of bacteria within host cells requires that they adapt to life in an intracellular environment. This adaptation induces bacterial stress through events such as phagocytosis and enhanced nutrient-restriction. During stress, bacteria synthesize a family of proteins known as heat shock proteins (HSPs) to facilitate adaptation and survival. Previously, we determined the Staphylococcus aureus HSP ClpC temporally alters bacterial metabolism and persistence. This led us to hypothesize that ClpC might alter intracellular survival. Inactivation of clpC in S. aureus strain DSM20231 significantly enhanced long-term intracellular survival in human epithelial (HaCaT) and endothelial (EA.hy926) cell lines, without markedly affecting adhesion or invasion. This phenotype was similar across a genetically diverse collection of S. aureus isolates, and was influenced by the toxin/antitoxin encoding locus mazEF. Importantly, MazEF alters mRNA synthesis and/or stability of S. aureus virulence determinants, indicating ClpC may act through the mRNA modulatory activity of MazEF. Transcriptional analyses of total RNAs isolated from intracellular DSM20231 and isogenic clpC mutant cells identified alterations in transcription of α-toxin (hla), protein A (spa), and RNAIII, consistent with the hypothesis that ClpC negatively affects the intracellular survival of S. aureus in non-professional phagocytic cells, via modulation of MazEF and Agr.

scholarly journals A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from FatalStaphylococcus aureusSepticemia

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Gowrisankar Rajam ◽  
Gabrielle M. Hammons ◽  
George M. Carlone ◽  
Jacquelyn S. Sampson ◽  
Edwin W. Ades
Keyword(s):  
Immune Therapy ◽  
Innate Immune ◽  
Control Group ◽  
Amino Acid Peptide ◽  
Resistant Strains ◽  
Immune Enhancement ◽  
Opsonophagocytic Killing ◽  
Drug Resistant Strains

Staphylococcus aureus(SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success. In this study, we demonstrate that P4, a 28-amino acid peptide, derived from pneumococcal surface adhesin A along with pathogen-specific antibody (IVIG; P4 therapy) is successful in enhancing the opsonophagocytic killing (OPK) ofS. aureus in vitro. We questioned if it is possible to expand P4 therapy to treat staphylococcal infectionsin vivo. P4 therapy in combination with IVIG rescued 7/10 morbidly illS. aureus-infected mice while only 2/10 survived in the control group.

scholarly journals Studies on the effects of 3-acetyl-4"-isovaleryltylosin against multiple-drug resistant strains of Staphylococcus aureus.

1981 ◽  
Vol 34 (3) ◽  
pp. 305-312 ◽  
Author(s):  
MASAMI TSUCHIYA ◽  
KAYOKO SUZUKAKE ◽  
MAKOTO HORI ◽  
TSUTOMU SAWA ◽  
TOMIO TAKEUCHI ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Multiple Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Chlamydophila psittaci in homing and feral pigeons and zoonotic transmission

2010 ◽  
Vol 59 (11) ◽  
pp. 1348-1353 ◽  
Author(s):  
V. Dickx ◽  
D. S. A. Beeckman ◽  
L. Dossche ◽  
P. Tavernier ◽  
D. Vanrompay
Keyword(s):  
Protein A ◽  
Homing Pigeon ◽  
Zoonotic Transmission ◽  
Antimicrobial Drugs ◽  
Homing Pigeons ◽  
Feral Pigeons ◽  
Chlamydophila Psittaci ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
The City

Chlamydiosis is a zoonotic disease in birds caused by Chlamydophila psittaci, an obligate intracellular bacterium. There are seven known avian outer-membrane protein A genotypes, A–F and E/B. The importance of genotyping lies in the fact that certain genotypes tend to be associated with certain hosts and a difference in virulence. Genotype B is the most prevalent in pigeons, but the more virulent genotypes A and D have also been discovered. The current study assessed the prevalence of C. psittaci in 32 Belgian homing-pigeon facilities and in 61 feral pigeons captured in the city of Ghent, Belgium. Additionally, zoonotic transmission of C. psittaci was investigated in the homing-pigeon facilities. Homing pigeons were often infected, as at least one of the lofts was positive in 13 of the 32 (40.6 %) pigeon breeding facilities. Genotypes B, C and D were detected. Zoonotic transmission was discovered in 4 of the 32 (12.5 %) pigeon fanciers, revealing genotype D in two of them, whilst genotyping was unsuccessful for the other two human pharyngeal swabs. This study clearly demonstrates the possible risk of C. psittaci zoonotic transmission from homing pigeons. Pigeon fanciers often (37.5 %) used antibiotics for prevention of respiratory disease. Because of the risk of developing drug-resistant strains, regular use of antimicrobial drugs must be avoided. This study is believed to be the first to detect C. psittaci in Belgian feral pigeons. The prevalence rate in the city of Ghent was extremely low, which is beneficial for public health.

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