Prevention of Panton-Valentine Toxin-Mediated Leucocyte Destruction Depending on the Ultra-Diluted Staphylococcinum Potency Gradient

2020 ◽  
Vol 33 (02) ◽  
pp. 099-103
Author(s):  
Pritam Goswami ◽  
Sayak Ghosh ◽  
Sk Swaif Ali ◽  
Anamika Basu ◽  
Joydeep Khanra ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ecological Niche ◽  
Staphylococcal Infection ◽  
Buffy Coat ◽  
Preventive Action ◽  
Phagocytic Cells ◽  
Mortality And Morbidity ◽  
Aureus Infection ◽  
The Mean

Abstract Background Panton-Valentine toxin (PVT) is an important pathological marker of staphylococcal infection mediated by functional as well as morphological damage of the phagocytic cells. Human body being an ecological niche for the bacteria shows higher affinity toward staphylococcal infection. A steady escalation in mortality and morbidity associated with antibiotic resistance in gram-positive infections is an emerging threat all over the globe; thus, it is important to find out an alternative strategy that can diminish the virulence and pathogenicity of the bacteria. Staphylococcin is a colicin-type chemical secreted by Staphylococcus aureus helps to prevent growth of organisms other than its progenitor. In this study, we evaluated the efficacy of homoeopathic medicine Staphylococcinum against staphylococcal PVT at different potencies (6CH, 12CH, 30CH and 200CH). Materials and Methods Different potencies of Staphylococcinum were administered in a leucocyte buffy coat preparation infected with staphylococcal suspension (0.5 McFarland's standard) along with control with alcohol. They were kept in incubator for 2 hours and then centrifuged at 1200 rpm for 5 minutes. Smears prepared on slides with centrifuged deposits stained by Preston and Morrell's modified Gram's method of staining and evaluated under the microscope. Results It was observed that there was extensive destruction of leukocytes in control and 6CH potency, while the degree of destruction decreased markedly from 12CH to 200CH. At 200CH potency, leukocytes were almost normal, which clearly indicate the preventive action of Staphylococcinum against PVT. The mean percentages of intact leucocytes were 0.73, 0.93, 10.00, 27.67 and 65.00 in control, 6CH, 12CH, 30CH and 200CH potencies, respectively. Conclusion The finding may help in the use of this medicine in moribund patients in cases of disseminated S. aureus infection as there is no known side effect of the medicine. However, in vivo study is necessary before such use in those cases.

scholarly journals T Cell Immunity and the Quest for Protective Vaccines against Staphylococcus aureus Infection

2020 ◽  
Vol 8 (12) ◽  
pp. 1936
Author(s):  
Erin Armentrout ◽  
George Liu ◽  
Gislâine Martins
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
Vaccine Trial ◽  
Preventive Measure ◽  
T Cell Subsets ◽  
Cell Mediated Immunity ◽  
Mortality And Morbidity ◽  
Aureus Infection ◽  
Cell Immunity ◽  
Causative Agents

Staphylococcus aureus is a wide-spread human pathogen, and one of the top causative agents of nosocomial infections. The prevalence of antibiotic-resistant S. aureus strains, which are associated with higher mortality and morbidity rates than antibiotic-susceptible strains, is increasing around the world. Vaccination would be an effective preventive measure against S. aureus infection, but to date, every vaccine developed has failed in clinical trials, despite inducing robust antibody responses. These results suggest that induction of humoral immunity does not suffice to confer protection against the infection. Evidence from studies in murine models and in patients with immune defects support a role of T cell-mediated immunity in protective responses against S. aureus. Here, we review the current understanding of the mechanisms underlying adaptive immunity to S. aureus infections and discuss these findings in light of the recent S. aureus vaccine trial failures. We make the case for the need to develop anti-S. aureus vaccines that can specifically elicit robust and durable protective memory T cell subsets.

In vivo photothermal inhibition of methicillin-resistant Staphylococcus aureus infection by in situ templated formulation of pathogen-targeting phototheranostics

Nanoscale ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 7651-7659 ◽  
Author(s):  
Xujuan Guo ◽  
Bing Cao ◽  
Congyu Wang ◽  
Siyu Lu ◽  
Xianglong Hu
Keyword(s):  
Staphylococcus Aureus ◽  
Magnetic Resonance ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Photoacoustic Imaging ◽  
Methicillin Resistant ◽  
Aureus Infection ◽  
Mrsa Infection ◽  
Efficient Elimination

Herein, pathogen-targeting phototheranostic nanoparticles, Van-OA@PPy, are in situ developed for efficient elimination of MRSA infection, which is reflected by dual-modality magnetic resonance and photoacoustic imaging.

scholarly journals Ceftobiprole EfficacyIn Vitroagainst Panton-Valentine Leukocidin Production andIn Vivoagainst Community-Associated Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rabbits

2012 ◽  
Vol 56 (12) ◽  
pp. 6291-6297 ◽  
Author(s):  
Azzam Saleh-Mghir ◽  
Oana Dumitrescu ◽  
Aurélien Dinh ◽  
Yassine Boutrad ◽  
Laurent Massias ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
The Mean ◽  
Mrsa Strains ◽  
Time Kill ◽  
Panton Valentine Leukocidin ◽  
Valentine Leukocidin

ABSTRACTCommunity-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) can cause osteomyelitis with severe sepsis and/or local complications in which a Panton-Valentine leukocidin (PVL) role is suspected.In vitrosub-MIC antibiotic effects on growth and PVL production by 11 PVL+MRSA strains, including the major CA-MRSA clones (USA300, including the LAC strain; USA400; and USA1000), and 11 PVL+methicillin-susceptibleS. aureus(MSSA) strains were tested in microplate culture. Time-kill analyses with ceftobiprole at its MIC were also run with LAC. Efficacies of ceftobiprole (40 mg/kg of body weight subcutaneously [s.c.] four times a day [q.i.d.]) or vancomycin (60 mg/kg intramuscularly [i.m.] twice a day [b.i.d.]) alone or combined with rifampin (10 mg/kg b.i.d.) against rabbit CA-MRSA osteomyelitis, induced by tibial injection of 3.4 × 107CFU of LAC, were compared. Treatment, started 14 days postinoculation, lasted 14 days.In vitro, 6/11 strains cultured with sub-MICs of ceftobiprole produced 1.6- to 4.8-fold more PVL than did the controls, with no link to specific clones. Rifampin decreased PVL production by all tested strains. In time-kill analyses at the LAC MIC (0.75 mg/liter), PVL production rose transiently at 6 and 8 h and then declined 2-fold at 16 h, concomitant with a 2-log10-CFU-count decrease.In vivo, the mean log10CFU/g of bone for ceftobiprole (1.44 ± 0.40) was significantly lower than that for vancomycin (2.37 ± 1.22) (P= 0.034), with 7/10 versus 5/11 bones sterilized, respectively. Combination with rifampin enhanced ceftobiprole (1.16 ± 0.04 CFU/g of bone [P= 0.056], 11/11 sterile bones) and vancomycin (1.23 ± 0.06 CFU/g [P= 0.011], 11/11 sterile bones) efficacies. Ceftobiprole bactericidal activity and the rifampin anti-PVL effect could play a role in these findings, which should be of interest for treating CA-MRSA osteomyelitis.

scholarly journals The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen‐reactivity to in vivo anergy

2011 ◽  
Vol 3 (11) ◽  
pp. 652-666 ◽  
Author(s):  
Christina Ziegler ◽  
Oliver Goldmann ◽  
Elias Hobeika ◽  
Robert Geffers ◽  
Georg Peters ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Aureus Infection ◽  
Antigen Reactivity

Antibacterial Effects of Derivatives of Porphyrin, Naphthalene diimide, Aminophenol and Benzodioxane on Methicillin Resistant Staphylococcus aureus and Neuropathogenic Escherichia coli K1

2020 ◽  
Vol 18 (3) ◽  
pp. 275-284
Author(s):  
Ruqaiyyah Siddiqui ◽  
Ayaz Anwar ◽  
Salwa Ali ◽  
Naveed Ahmed Khan
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Antimicrobial Properties ◽  
Antibacterial Activities ◽  
Host Cells ◽  
Mortality And Morbidity ◽  
Naphthalene Diimide ◽  
Molecular Mode ◽  
Escherichia Coli K1

Background: Infectious diseases contribute to substantial mortality and morbidity worldwide despite advances in therapeutic intervention highlighting the need to identify drugs with antimicrobial properties. Methods: Here, we utilised several compounds from the following classes: porphyrin, naphthalene diimide, aminophenol derivatives, and benzodioxane, and evaluated their antibacterial activities. Bactericidal and bacteriostatic activity of these compounds were determined against methicillinresistant Staphylococcus aureus (MRSA) and Escherichia coli K1 with various concentrations of the drugs. Moreover, the ability of the bacteria to bind/associate to host cells was also ascertained in the absence and presence of aforementioned compounds. Results: The results revealed that porphyrin derivative (AYTHPP) had potent effects against MRSA, abolishing viability and blocking binding to the host cells. Importantly, novel AYTHPP exhibited powerful effects against MRSA even though it was not photoactivated. In contrast, other compounds, including naphthalene diimide, acetamol derivatives and benzodioxane, showed no inhibitory effects. Conclusion: The mechanism of action of porphyrin is likely through the production of reactive oxygen species causing oxidative stress, leading to apoptosis and/or necrosis via perturbations in the plasma membrane. Future studies will determine their in vivo efficacy together will associated molecular mode of action.

IN VIVO STUDIES ON ANTISTAPHYLOCOCCAL PENICILLINASE SERUM

1964 ◽  
Vol 10 (4) ◽  
pp. 507-512
Author(s):  
M. Goldner ◽  
R. J. Wilson
Keyword(s):  
Staphylococcus Aureus ◽  
Combined Treatment ◽  
Rabbit Antiserum ◽  
Staphylococcal Infection ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Single Strain ◽  
Lethal Doses ◽  
Observation Period

Several workers have shown that laboratory animals are protected from penicillin-resistant Staphylococcus aureus infections by antiserum to Bacillus cereus penicillinase in conjunction with benzylpenicillin. This paper shows that antiserum to staphylococcal penicillinase has the same effect. Concentrated penicillinase from a single strain of staphylococcus was used to prepare a rabbit antiserum. Groups of rabbits were injected intravenously with lethal doses of the same strain of staphylococcus. They were either given no treatment or were treated with penicillin only, antiserum only, or combined penicillin and antiserum. Antiserum was given in a single dose or in multiple doses. Throughout the 3-week observation period, the mortality in the group of rabbits receiving combined treatment was significantly less than in any other group. It was concluded that it might be possible to use antistaphylococcal penicillinase serum in the treatment of penicillin-resistant staphylococcal infection.

Adaptation of the Staphylococcus aureus leukocidin LukGH for the rabbit host by protein engineering

2019 ◽  
Vol 476 (2) ◽  
pp. 275-292 ◽  
Author(s):  
Nikolina Trstenjak ◽  
Lukas Stulik ◽  
Harald Rouha ◽  
Jakub Zmajkovic ◽  
Manuel Zerbs ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Animal Models ◽  
Small Animal ◽  
Receptor Interaction ◽  
Polymorphonuclear Cells ◽  
Bacterial Clearance ◽  
Phagocytic Cells ◽  
Aureus Infection ◽  
Small Animal Models

AbstractHost defense against Staphylococcus aureus greatly depends on bacterial clearance by phagocytic cells. LukGH (or LukAB) is the most potent staphylococcal leukocidin towards human phagocytes in vitro, but its role in pathogenesis is obscured by the lack of suitable small animal models because LukGH has limited or no cytotoxicity towards rodent and rabbit compared with human polymorphonuclear cells (PMNs) likely due to an impaired interaction with its cellular receptor, CD11b. We aimed at adapting LukGH for the rabbit host by improving binding to the rabbit homolog of CD11b, specifically its I-domain (CD11b-I). Targeted amino acid substitutions were introduced into the LukH polypeptide to map its receptor interaction site(s). We found that the binding affinity of LukGH variants to the human and rabbit CD11b-I correlated well with their PMN cytotoxicity. Importantly, we identified LukGH variants with significantly improved cytotoxicity towards rabbit PMNs, when expressed recombinantly (10–15-fold) or by engineered S. aureus strains. These findings support the development of small animal models of S. aureus infection with the potential for demonstrating the importance of LukGH in pathogenesis.

DEGRADATION OF PENICILLIN G AND THREE SEMISYNTHETIC PENICILLINS BY BACILLUS CEREUS AND STAPHYLOCOCCUS AUREUS PENICILLINASE

1966 ◽  
Vol 12 (1) ◽  
pp. 35-42 ◽  
Author(s):  
J. A. Yurchenco ◽  
M. W. Hopper ◽  
G. H. Warren
Keyword(s):  
Staphylococcus Aureus ◽  
Bacillus Cereus ◽  
Enzymatic Degradation ◽  
Penicillin G ◽  
Aureus Infection ◽  
Penicillanic Acid ◽  
Potassium Penicillin ◽  
And Staphylococcus Aureus

An in vivo procedure is described for determining the relative sensitivities of potassium penicillin G and three semisynthetic penicillins to degradation by Bacillus cereus and Staphylococcus aureus penicillinases. The inactivating concentrations (IC50) of the penicillinases necessary to reduce the protective activity of each of the penicillins against an S. aureus infection in mice from PD95 to a PD50 level was determined. Conventional in vitro studies were carried out for purposes of comparison. After interaction with B. cereus penicillinase, Wy-3206 [6-(2-methoxy-1-naphthamido) penicillanic acid] had the greatest residual therapeutic activity, followed in order by nafcillin [6-(2-ethoxy-1-naphthamido)penicillanic acid], methicillin [sodium 6-(2, 6-dimethoxybenzamido)penicillinate monohydrate], and potassium penicillin G. Penicillin G proved to be the most sensitive to enzymatic degradation by S. aureus penicillinase, whereas nafcillin and methicillin were resistant to the highest concentration employed. These findings were, in general, supported by the in vitro results.

scholarly journals Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

2014 ◽  
Vol 82 (9) ◽  
pp. 3588-3598 ◽  
Author(s):  
Stacey X. Xu ◽  
Kevin J. Gilmore ◽  
Peter A. Szabo ◽  
Joseph J. Zeppa ◽  
Miren L. Baroja ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Pathogen ◽  
Staphylococcal Infection ◽  
Infection Process ◽  
Interleukin 12 ◽  
Bacterial Survival ◽  
Content Type ◽  
Knockout Strain ◽  
Neutrophil Response

ABSTRACTStaphylococcus aureusis a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection withS. aureusNewman induced SEA-dependent Vβ skewing of T cells and enhanced bacterial survival in the liver compared with infection byseaknockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b+Ly6G+neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently inS. aureusNewman-infected livers than in livers infected with the Newmanseaknockout strain, promoting the survival ofS. aureusin vivo. This represents a novel mechanism during infection wherebyS. aureusutilizes SAgs to form a specialized niche and manipulate the immune system.

Liu Shen Wan inhibits influenza virus-induced secondary Staphylococcus aureus infection in vivo and in vitro

2021 ◽  
pp. 114066
Author(s):  
Jin Zhao ◽  
Xiaodong Huang ◽  
Yutao Wang ◽  
Qinhai Ma ◽  
Jian Song ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Influenza Virus ◽  
Aureus Infection
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