scholarly journals Polyketides from marine-derived Aspergillus welwitschiae inhibit Staphylococcus aureus virulence factors and potentiate vancomycin antibacterial activity in vivo

2020 ◽  
Vol 143 ◽  
pp. 104066 ◽  
Author(s):  
Luciana A. Loges ◽  
Denise B. Silva ◽  
Gustavo V.B. Paulino ◽  
Melissa F. Landell ◽  
Alexandre J. Macedo
2018 ◽  
Vol 7 (4) ◽  
pp. 392-398
Author(s):  
B.T Yunana ◽  
◽  
B. B Bukar ◽  
J. C Aguiyi ◽  
◽  
...  

The ethanol extracts of root, bark and leaf of Bridelia ferruginea was investigated for antibacterial activity against clinical isolate of Staphylococcus aureus and Escherichia coli. The extracts had significant antibacterial activity in vitro at concentration of 25 mg/ml, 50 mg/ml, 100 mg/ml and 200 mg/ml and in vivo at dose of 50 mg/kg and 100 mg/kg. The root extract in vitro had the highest zone of inhibition, followed by the bark extract for both Staphylococcus aureus and Escherichia coli. The concentration of 200 mg/ml had the highest zone of inhibition in vitro. The minimum inhibitory concentration (MIC) showed a decreasing inhibitory effect of the plant extracts for both Staphylococcus aureus and Escherichia coli as the concentration decreases with root having 3.125 mg/ml, bark having 6.25 mg/ml and leaf having 25 mg/ml for Staphylococcus aureus and Escherichia coli. Likewise, the minimum bactericidal concentration (MBC) showed decreasing bactericide effects with decrease concentration with root having 12.5 mg/ml, bark having 12.5 mg/ml and leaf having 25 mg/ml for Escherichia coli while root had 6.25mg/ml, bark had 12.5mg/ml and leaf had 25mg/ml for Staphylococcus aureus. The in vivo investigation showed that the root and bark extract exhibited antibacterial activity on both Staphylococcus aureus and Escherichia coli at doses of 100mg/kg and 50mg/kg; the root extract had higher activity than the bark and root/bark combined. The dose of 100 mg/kg had the highest colonies reduction for Staphylococcus aureus and Escherichia coli in vivo. Preliminary phytochemical screening of root, bark and leaves of Bridelia ferruginea revealed the presence of tannins, flavonoids, carbohydrates, cardiac glycoside (root, bark and leaves), saponins (root and bark). The presence of tannins, saponins, flavonoid, cardiac glycoside and carbohydrate in the bark and root extracts of the plant indicates that the bark and root extracts were pharmacological importance


2019 ◽  
Vol 116 (27) ◽  
pp. 13563-13572 ◽  
Author(s):  
William E. Sause ◽  
Divya Balasubramanian ◽  
Irnov Irnov ◽  
Richard Copin ◽  
Mitchell J. Sullivan ◽  
...  

The pathogen Staphylococcus aureus colonizes and infects a variety of different sites within the human body. To adapt to these different environments, S. aureus relies on a complex and finely tuned regulatory network. While some of these networks have been well-elucidated, the functions of more than 50% of the transcriptional regulators in S. aureus remain unexplored. Here, we assess the contribution of the LacI family of metabolic regulators to staphylococcal virulence. We found that inactivating the purine biosynthesis regulator purR resulted in a strain that was acutely virulent in bloodstream infection models in mice and in ex vivo models using primary human neutrophils. Remarkably, these enhanced pathogenic traits are independent of purine biosynthesis, as the purR mutant was still highly virulent in the presence of mutations that disrupt PurR’s canonical role. Through the use of transcriptomics coupled with proteomics, we revealed that a number of virulence factors are differentially regulated in the absence of purR. Indeed, we demonstrate that PurR directly binds to the promoters of genes encoding virulence factors and to master regulators of virulence. These results guided us into further ex vivo and in vivo studies, where we discovered that S. aureus toxins drive the death of human phagocytes and mice, whereas the surface adhesin FnbA contributes to the increased bacterial burden observed in the purR mutant. Thus, S. aureus repurposes a metabolic regulator to directly control the expression of virulence factors, and by doing so, tempers its pathogenesis.


Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2954
Author(s):  
Yangli Wan ◽  
Xiaowen Wang ◽  
Pengfei Zhang ◽  
Meng Zhang ◽  
Mingying Kou ◽  
...  

Foodborne Staphylococcus aureus (S. aureus) has attracted widespread attention due to its foodborne infection and food poisoning in human. Shikonin exhibits antibacterial activity against a variety of microorganisms, but there are few studies on its antibacterial activity against S. aureus. This study aims to explore the antibacterial activity and mechanism of shikonin against foodborne S. aureus. The results show that the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of shikonin were equal for all tested strains ranging from 35 μg/mL to 70 μg/mL. Shikonin inhibited the growth of S. aureus by reducing intracellular ATP concentrations, hyperpolarizing cell membrane, destroying the integrity of cell membrane, and changing cell morphology. At the non-inhibitory concentrations (NICs), shikonin significantly inhibited biofilm formation of S. aureus, which was attributed to inhibiting the expression of cidA and sarA genes. Moreover, shikonin also markedly inhibited the transcription and expression of virulence genes (sea and hla) in S. aureus. In addition, shikonin has exhibited antibacterial ability against both planktonic and biofilm forms of S. aureus. Importantly, in vivo results show that shikonin has excellent biocompatibility. Moreover, both the heat stability of shikonin and the antimicrobial activity of shikonin against S. aureus were excellent in food. Our findings suggest that shikonin are promising for use as a natural food additive, and it also has great potential in effectively controlling the contamination of S. aureus in food and reducing the number of illnesses associated with S. aureus.


2010 ◽  
Vol 54 (8) ◽  
pp. 3478-3480 ◽  
Author(s):  
Michael J. Pucci ◽  
Maria Ackerman ◽  
Jane A. Thanassi ◽  
Carolyn M. Shoen ◽  
Michael H. Cynamon

ABSTRACT ACH-702 is a new isothiazoloquinolone with potent in vitro and in vivo activities against important bacterial pathogens, including Staphylococcus aureus. In this study, ACH-702 was found to have promising in vitro antibacterial activity against Mycobacterium tuberculosis, with MICs of ≤1 μg/ml, comparable to that of the fluoroquinolone moxifloxacin for quinolone-susceptible isolates but superior to that for quinolone-resistant isolates. Biochemical assays involving M. tuberculosis gyrase enzymes indicated that ACH-702 had significantly improved inhibitory activity compared with fluoroquinolones.


2003 ◽  
Vol 47 (8) ◽  
pp. 2507-2512 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Morio Takema ◽  
Hideaki Miwa ◽  
Jingoro Shimada ◽  
Shogo Kuwahara

ABSTRACT The in vivo antibacterial activity of S-3578, a new parental cephalosporin, was compared with those of cefepime, ceftriaxone, ceftazidime, imipenem-cilastatin, and vancomycin. The efficacy of S-3578 against systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) SR3637 (50% effective dose [ED50], 7.21 mg/kg of body weight) was almost the same as that of vancomycin. In contrast, cefepime and imipenem-cilastatin were less active against this pathogen (ED50s, >100 and >100 mg/kg, respectively). S-3578 was the most effective compound against penicillin-resistant Streptococcus pneumoniae SR20946 (ED50, 1.98 mg/kg). S-3578 (10 mg/kg) induced a significant reduction in the numbers of viable MRSA SR17764 and Pseudomonas aeruginosa SR10396 organisms in polymicrobial pulmonary infections. The therapeutic efficacy of S-3578 was more potent than that of the combination of vancomycin and ceftazidime. High levels of S-3578 were detected in plasma in vivo, and its efficacy against experimentally induced infections in mice caused by MRSA and P. aeruginosa reflected its potent in vitro activity. We conclude that S-3578 is a promising new cephalosporin for the treatment of infections caused by gram-positive and -negative bacteria, including MRSA and P. aeruginosa.


2009 ◽  
Vol 54 (1) ◽  
pp. 170-176 ◽  
Author(s):  
Wei-Tao Jia ◽  
Shi-Hua Luo ◽  
Chang-Qing Zhang ◽  
Jian-Qiang Wang

ABSTRACT The i n vitro and in vivo therapeutic efficacies of teicoplanin-loaded calcium sulfate (TCS; 10% [wt] teicoplanin) were investigated in a rabbit model of chronic methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. The in vitro elution characteristics of teicoplanin from TCS pellets were realized by carrying out an evaluation of the release kinetics, recovery rate, and antibacterial activity of the released teicoplanin. Chronic osteomyelitis was induced by inoculating 107 CFU of a MRSA strain into the tibial cavity of rabbits. After 3 weeks, the animals were treated by debridement followed by implantation of TCS pellets in group 1, calcium sulfate (CS) pellets alone in group 2, and intravenous (i.v.) teicoplanin (6 mg/kg of body weight every 12 h for three doses and then every 24 h up to 4 weeks) in group 3. Animals in group 4 were left untreated. After 6 weeks, the efficacy of the osteomyelitis treatment was evaluated by hematological, radiological, microbiological, and histological examinations. In vitro elution studies showed sustained release of teicoplanin at a therapeutic level over a time period of 3 weeks. The released teicoplanin maintained its antibacterial activity. In vivo, the best therapeutic effect was observed in animals treated with TCS pellets, resulting in significantly lower radiological and histological scores, lower positive rates of MRSA culture and bacterial load, and excellent bone regeneration compared with those treated by CS alone or i.v. teicoplanin, without any local or systemic adverse effects. TCS pellets are an effective alternative to i.v. teicoplanin for the treatment of chronic MRSA osteomyelitis, particularly because teicoplanin is delivered locally while the TCS pellets simultaneously promote bone defect repair.


2017 ◽  
Vol 30 (4) ◽  
pp. 887-917 ◽  
Author(s):  
Elisabeth Hodille ◽  
Warren Rose ◽  
Binh An Diep ◽  
Sylvain Goutelle ◽  
Gerard Lina ◽  
...  

SUMMARY Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Masaya Ueno ◽  
Hiroshi Miyamoto ◽  
Masatsugu Tsukamoto ◽  
Shuichi Eto ◽  
Iwao Noda ◽  
...  

Biofilm-producing bacteria are the principal causes of infections associated with orthopaedic implants. We previously reported that silver-containing hydroxyapatite (Ag-HA) coatings exhibit high antibacterial activity against methicillin-resistantStaphylococcus aureus(MRSA). In the present study, we evaluated the effects of Ag-HA coating of implant surfaces on biofilm formation. Titanium disks (14-mm diameter, 1-mm thickness), one surface of which was coated with HA or 0.5%–3.0% Ag-HA with a thermal spraying technique, were used. In vitro, the disks were inoculated with an MRSA suspension containing4×105 CFU and incubated for 1-2 weeks. In vivo, MRSA-inoculated HA and 3% Ag-HA disks (8.8–10.0 × 108 CFU) were implanted subcutaneously on the back of rats for 1–7 days. All disks were subsequently stained with a biofilm dye and observed under a fluorescence microscope, and biofilm coverage rates (BCRs) were calculated. The BCRs on the Ag-HA coating were significantly lower than those on the HA coating at all time points in vitro (p<0.05). Similar results were observed in vivo (p<0.001) without argyria. Ag-HA coating reduced biofilm formation by MRSA in vitro and in vivo; therefore, Ag-HA coating might be effective for reducing implant-associated infections.


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