Tryptophan metabolism and toxin formation in Staphylococcus aureus Wood 46 strain

1969 ◽  
Vol 15 (1) ◽  
pp. 1-7 ◽  
Author(s):  
T. Leboeuf-Trudeau ◽  
J. de Repentigny ◽  
R. M. Frenette ◽  
S. Sonea
Keyword(s):  
Staphylococcus Aureus ◽  
Hemolytic Activity ◽  
Shikimic Acid ◽  
Tryptophan Depletion ◽  
Alpha Toxin ◽  
Predominant Role ◽  
Toxic Material ◽  
Chorismic Acid ◽  
Culture Supernatants

Tryptophan analogs known to act selectively on protein synthesis were used to study the effects of tryptophan depletion on the formation of Staphylococcus aureus (Wood 46 strain) toxic material. The production of toxin during growth and its presence in culture supernatants were followed by determining alpha hemolytic activity in rabbit blood agar, lethality for mice, and immunodiffusion patterns with staphylococcal antitoxins. The following results were obtained when the bacteria were grown in the presence of 4- and 5-methyltryptophans and 7-azatryptophan: (1) growth inhibition from 20 to 50%; (2) loss of alpha hemolytic activity; (3) inability of culture supernatants to kill mice; (4) decrease in the number of antigens precipitating with staphylococcal antitoxin and absence of reaction with purified alpha antitoxin. No significant effects were observed with 5-fluorotryptophan; 6-methyltryptophan was totally inactive. All inhibitions were reversed by L-tryptophan, anthranilic acid, and indole, but only partially by chorismic acid, and not at all by shikimic acid. These observations are suggestive of a predominant role of L-tryptophan in the synthesis of staphylococcal alpha toxin.

scholarly journals Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 343 ◽  
Author(s):  
Keogh ◽  
Zapf ◽  
Trzeciak ◽  
Null ◽  
Wiemels ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Protein Secretion ◽  
Virulence Determinants ◽  
Bacterial Survival ◽  
Alpha Toxin ◽  
Cellular Targets ◽  
Significant Difference ◽  
Culture Supernatants

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a ppiB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the ppiB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a ppiB mutant strain has reduced levels of the phenol-soluble modulins and that both ppiB and prsA mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PpiB and PrsA. Results suggest a novel role for PpiB in S. aureus protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence S. aureus toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease.

scholarly journals Rabbit erythrocyte band 3: a receptor for staphylococcal alpha toxin

1980 ◽  
Vol 26 (4) ◽  
pp. 524-531 ◽  
Author(s):  
Indar Maharaj ◽  
Hugh B. Fackrell
Keyword(s):  
Molecular Weight ◽  
Staphylococcus Aureus ◽  
Affinity Chromatography ◽  
Concanavalin A ◽  
Hemolytic Activity ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Band 3 ◽  
Alpha Toxin ◽  
Rabbit Erythrocyte

Enzymes known to specifically cleave the band 3 component of the rabbit erythrocyte membrane were found to reduce both the hemolytic sensitivity to and the binding of the alpha toxin of Staphylococcus aureus. Lectins which bind to band 3 also inhibited the toxin. Lectins which do not bind to band 3 have no effect. Purified band 3, isolated by affinity chromatography on a concanavalin A column, was homogeneous by polyacrylamide gel electrophoresis, had a molecular weight of 100 000, and inhibited the hemolytic activity of alpha toxin. Antibodies to the toxin–toxoid receptor were serologically indistinguishable from antiband 3.

scholarly journals Increased Risk of Thrombocytopenia and Death in Patients with Bacteremia Caused by High Alpha Toxin-Producing Methicillin-Resistant Staphylococcus aureus

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 726
Author(s):  
Fatimah Alhurayri ◽  
Edith Porter ◽  
Rachid Douglas-Louis ◽  
Emi Minejima ◽  
Juliane Bubeck Wardenburg ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Data ◽  
Hemolytic Activity ◽  
Strongly Correlated ◽  
Alpha Toxin ◽  
Hemolysis Assay ◽  
Normal Platelet ◽  
Increased Risk ◽  
Mrsa Strains

Alpha toxin (Hla) is a major virulence factor of Staphylococcus aureus that targets platelets but clinical data on Hla pathogenesis in bacteremia (SAB) is limited. We examined the link between in vitro Hla activity and outcome. Study isolates obtained from 100 patients with SAB (50 survivors; 50 non-survivors) were assessed for in vitro Hla production by Western immunoblotting in a subset of isolates and Hla activity by hemolysis assay in all isolates. Relevant demographics, laboratory and clinical data were extracted from patients’ medical records to correlate Hla activity of the infecting isolates with outcome. Hla production strongly correlated with hemolytic activity (rs = 0.93) in vitro. A trend towards higher hemolytic activity was observed for MRSA compared to MSSA and with high-risk source infection. Significantly higher hemolytic activity was noted for MRSA strains isolated from patients who developed thrombocytopenia (median 52.48 vs. 16.55 HU/mL in normal platelet count, p = 0.012) and from non survivors (median 30.96 vs. 14.87 HU/mL in survivors, p = 0.014) but hemolytic activity of MSSA strains did not differ between patient groups. In vitro Hla activity of MRSA strains obtained from patients with bacteremia is significantly associated with increased risk for thrombocytopenia and death which supports future studies to evaluate feasibility of bedside phenotyping and therapeutic targeting.

Further observations on the mode of action of the alpha toxin of Staphylococcus aureus "Wood-46"

1972 ◽  
Vol 18 (7) ◽  
pp. 987-992 ◽  
Author(s):  
G. M. Wiseman ◽  
J. D. Caird
Keyword(s):  
Staphylococcus Aureus ◽  
Erythrocyte Membrane ◽  
Proteolytic Activity ◽  
Hemolytic Activity ◽  
Mode Of Action ◽  
Supernatant Fluid ◽  
Alpha Toxin ◽  
Rabbit Erythrocyte ◽  
Inhibitory Ability

Further evidence has been obtained which supports the view that alpha toxin from Staphylococcus aureus "Wood 46" is a protease which requires activation by erythrocyte membrane proteases. Rabbit erythrocyte antiprotease prepared in mice inhibited degradation of rabbit ghosts by the toxin. Supernatant fluid of toxin-treated ghosts incubated with EDTA and then passed through a column of Sephadex G-75 yielded a fraction which was hemolytic and proteolytic. These activities were both neutralized by alpha antitoxin prepared in rabbits, but not by control sera.It was also observed that alpha antitoxin inhibited the proteolytic activity of rabbit ghosts not exposed to toxin, in contrast with control sera. Inhibitory ability was removed from the antitoxin by adsorption with a heavy suspension of ghosts, and this treatment destroyed the antitoxin's capacity to neutralize hemolytic activity of the alpha toxin.

scholarly journals Mutation of traP in Staphylococcus aureus Has No Impact on Expression of agr or Biofilm Formation

2007 ◽  
Vol 75 (9) ◽  
pp. 4528-4533 ◽  
Author(s):  
Laura H. Tsang ◽  
Sonja T. Daily ◽  
Elizabeth C. Weiss ◽  
Mark S. Smeltzer
Keyword(s):  
Staphylococcus Aureus ◽  
Hemolytic Activity ◽  
Biofilm Formation ◽  
Laboratory Strain ◽  
Clinical Isolates ◽  
Regulatory Role ◽  
Accessory Gene ◽  
Accessory Gene Regulator ◽  
Affect Expression

ABSTRACT To investigate the regulatory role of traP (target of RNAIII-activating peptide) in Staphylococcus aureus, we generated traP mutations in the clinical isolates UAMS-1 and USA300. In neither case did mutation of traP affect expression of the accessory gene regulator (agr) or the ability to form a biofilm. We were also unable to confirm that mutation of traP in the prototype 8325-4 laboratory strain RN6390 results in reduced expression of agr, reduced hemolytic activity, or an altered capacity to form a biofilm.

Interactions entre Staphylococcus aureus et Pseudomonas aeruginosa dans des cultures in vitro et au cours d'infections expérimentales

1972 ◽  
Vol 18 (10) ◽  
pp. 1531-1541 ◽  
Author(s):  
J. de Repentigny ◽  
L. G. Mathieu ◽  
T. Gadbois
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Pure Culture ◽  
Maximum Growth ◽  
Mixed Cultures ◽  
Mixed Infections ◽  
Alpha Toxin ◽  
Culture Supernatants

Staphylococcus aureus and Pseudomonas aeruginosa are often found in succession or in association in infections. To study experimentally their interactions, we have used systems of growth or survival of mixed cultures of both species in vitro in a semisynthetic medium and in vivo in the peritoneal cavity of mice. Conditions for maximum growth in vitro of both species in mixed cultures are about similar to those in pure culture when the pH is maintained between 6.0 and 7.3. The inhibition of S. aureus growth by some antimetabolites or antibiotics, e.g., 5-methyltryptophan and D-cycloserine, is antagonized in mixed cultures. Staphylococcus coagulase, DNase, and alpha toxin were present either in mixed cultures or after mixing pure culture supernatants of both species, but P. aeruginosa slime was not observed in these conditions. In vivo, the survival of S. aureus seemed greater in mixed infections with P. aeruginosa than in those with S. aureus alone. In our systems, S. aureus may have benefited from the presence of P. aeruginosa whereas the reverse was not observed. These observations on interbacterial ecology could help to explain the importance and the behavior of some species at the initiation of pyogenic infections, either their interactions or their selection.

scholarly journals Increased risk of thrombocytopenia and death in patients with bacteremia caused by high alpha toxin-producing methicillin-resistant Staphylococcus aureus.

2021 ◽  
Author(s):  
Fatimah Alhurayri ◽  
Edith Porter ◽  
Rachid Douglas-Louis ◽  
Emi Minejima ◽  
Juliane Bubeck Wardenburg ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Data ◽  
Hemolytic Activity ◽  
Strongly Correlated ◽  
Alpha Toxin ◽  
Hemolysis Assay ◽  
Normal Platelet ◽  
Increased Risk ◽  
Mrsa Strains

Background: Alpha toxin (Hla) is a major virulence factor of Staphylococcus aureus that targets platelets but clinical data on Hla pathogenesis in bacteremia (SAB) is limited. Objective: We examined the link between in vitro Hla activity and outcome. Methods: Study isolates obtained from 100 patients with SAB (50 survivors; 50 non-survivors) were assessed for in vitro Hla production and activity by Western immunoblotting and hemolysis assay, respectively. Relevant demographics, laboratory and clinical data were extracted from patients' medical records to correlate Hla activity of the infecting isolates with outcome. Results: Hla production strongly correlated with hemolytic activity (rs=0.93) in vitro. A trend towards higher hemolytic activity was observed for MRSA compared to MSSA and with high-risk source infection. Significantly higher hemolytic activity was noted for MRSA strains isolated from patients who developed thrombocytopenia (median 52.48 vs 16.55 HU/ml in normal platelet count, p=0.012) and from non survivors (median 30.96 vs 14.87 HU/ml in survivors, p= 0.014) but hemolytic activity of MSSA strains did not differ between patient groups. Conclusions: In vitro Hla activity of S. aureus strains obtained from patients with bacteremia may be used to predict risk for thrombocytopenia and death which supports bedside phenotyping and therapeutic targeting in the future.

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