Baicalein mediates protection against Staphylococcus aureus-induced pneumonia by inhibiting the coagulase activity of vWbp.

The emergence and spread of multidrug-resistant Staphylococcus aureus (S. aureus) necessitate the research on therapeutic tactics which are different from classical antibiotics in overcoming resistance andtreatinginfections. In S. aureus, von Willebrand factor-binding protein (vWbp) is one of the key virulence determinants because it mediates not only the activation of thrombin to convert fibrinogen to fibrin, thereby enabling S. aureus to escape from the host immune clearance, but also the adhesion of S. aureus to host cells. Thus, vWbp is regarded as a promising druggable target to treat S. aureus-associated infections. Here we identify that baicalein, a natural compound isolated from the Chinese herb Scutellaria baicalensis, can effectively block the coagulase activity of vWbp without inhibiting the growth of the bacteria. Through thermal shift and fluorescence quenching assays, we demonstrated that baicalein directly binds to vWbp. Molecular dynamics simulations and mutagenesis assays revealed that the Asp-75 and Lys-80 residues are necessary for baicalein binding to vWbp. Importantly, we demonstrated that baicalein treatment attenuates the virulence of S. aureus and protects mice from S. aureus-induced lethal pneumonia. In addition, baicalein can improve the therapeutic effect of penicillin G by 75% in vivo. These findings indicate that baicalein might be developed as a promising therapeutic agent against drug-resistant S. aureus infections.

Effectual components of Polygonum ciliinerve protects against Staphylococcus aureus infection with immunomodulatory functions in C57BL/6 mice1.

PURPOSE: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. METHODS: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. RESULTS: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. CONCLUSION: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.

Effectual components of Polygonum ciliinerve protects against Staphylococcus aureus infection with immunomodulatory functions in C57BL/6 mice

Abstract Purpose: To investigate the efficacy and mechanisms of root tuber of Polygonum ciliinerve (Nakai) ohwi (rPC) which has been used to treat bacterial infection in traditional Chinese medicine. Methods: With the mouse model of Staphylococcus aureus (S. aureus) pneumonia, the phenotype of rPC treated mice, including body weight, mortality, lung slices and bacterial burden were evaluated. Furthermore, inflammatory factors in bronchoalveolar lavage (BAL) were determined by ELISA and the distribution of T cells in lung was assessed by immunofluorescence assay. Results: rPC treatment could dose-dependently reduce weight loss and mortality in S. aureus-infected mice. Upon 10 mg/ml rPC treatment, S. aureus-infected mice showed about 8 grams increase in body weight (P<0.001) and 50% enhancement in mortality. The integrity of lung tissue and bacterial burden were also improved by rPC treatment. Moreover, rPC was found to modulate the immune response in infection. Conclusion: rPC has therapeutic potential for S. aureus infections and pneumonia with immunomodulatory functions.

Isoalantolactone protects against Staphylococcus aureus pneumonia.

Staphylococcus aureus is a versatile pathogen that can cause life-threatening infections. The growing emergence of methicillin-resistant S. aureus strains and a decrease in the discovery of new antibiotics warrant the search for new therapeutic targets to combat infections. Staphylococcus aureus produces many extracellular virulence factors that contribute to its pathogenicity. Therefore, targeting bacterial virulence as an alternative strategy to the development of new antimicrobials has gained great interest. α-Toxin is a 33.2-kDa, water-soluble, pore-forming toxin that is secreted by most S. aureus strains. α-Toxin is essential for the pathogenesis of pneumonia, as strains lacking α-toxin display a profound defect in virulence. In this report, we demonstrate that isoalantolactone (IAL), a naturally occurring compound found in Inula helenium (Compositae), has no anti-S. aureus activity as per MIC evaluation in vitro. However, IAL can markedly inhibit the expression of α-toxin in S. aureus at very low concentrations. Furthermore, the in vivo data indicate that treatment with IAL protects mice from S. aureus pneumonia.

The effect of vitamin E on secondary bacterial infection after influenza infection in young and old mice.

Mortality from influenza is high in the elderly. Deaths are mainly due to secondary complications, including Staphylococcus aureus (SA) infections. Vitamin E (E) supplementation reduces influenza in aged mice. This study determined the efficacy of E supplementation on secondary bacterial infections after influenza in young and old mice. C57BL/6 mice were fed diets containing 30 or 500 ppm E for 4 weeks. Priming with influenza significantly increased SA in the lungs of infected mice fed control diet. Age did not have a significant effect on SA infection alone or SA infection after influenza infection. E supplementation did not have a significant effect on SA infection alone. However, E supplementation abolished the priming effect of influenza on SA.

Trimethoprim-sulfamethoxazole for the prevention of methicillin-resistant Staphylococcus aureus pneumonia in severely burned patients.

BACKGROUND: Patients with severe burns are at increased risk of developing methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia. This study was designed to determine whether MRSA pneumonia can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). METHODS: We conducted a prospective, randomized, placebo-controlled study in patients with severe burns (> or = 20%), who required ventilator support. Prophylaxis was done with oral TMP-SMX (80 mg/400 mg) three times daily for 10 days from 4 to 6 days after burn injury. The incidence of MRSA pneumonia and the side effects were evaluated during the administration period. RESULTS: Twenty-one patients were assigned to receive TMP-SMX, and 19 patients to receive placebo. The incidence of MRSA pneumonia was 4.8% in the TMP-SMX group and 36.8% in the placebo group, showing a significant difference (p = 0.017). No major side effects of therapy were seen in the TMP-SMX group. CONCLUSION: Prophylactic treatment with TMP-SMX can prevent MRSA pneumonia in severely burned patients.