Chinese herbal medicines and nutraceuticals inhibit Pseudomonas aeruginosa biofilm formation.
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ABSTRACT:
SUBMITTER: Hayashi M
PROVIDER: S-EPMC8650844 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Caseinolytic proteases (Clp) are central to bacterial proteolysis and control cellular physiology and stress responses. They are composed of a double-ring compartmentalized peptidase (ClpP) and a AAA+ unfoldase (ClpX or ClpA/ClpC). Unlike many bacteria, the opportunistic pathogen Pseudomonas aeruginosa contains two ClpP homologs: ClpP1 and ClpP2. The specific functions of these homologs, however, are largely elusive. Here, we report that the active form of PaClpP2 is a part of a heteromeric PaClpP17 P27 tetradecamer that is required for proper biofilm development. PaClpP114 and PaClpP17 P27 complexes exhibit distinct peptide cleavage specificities and interact differentially with P. aeruginosa ClpX and ClpA. Crystal structures reveal that PaClpP2 has non-canonical features in its N- and C-terminal regions that explain its poor interaction with unfoldases. However, experiments in vivo indicate that the PaClpP2 peptidase active site uniquely contributes to biofilm development. These data strongly suggest that the specificity of different classes of ClpP peptidase subunits contributes to the biological outcome of proteolysis. This specialized role of PaClpP2 highlights it as an attractive target for developing antimicrobial agents that interfere specifically with late-stage P. aeruginosa development.
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Project description:BackgroundHypercholesterolemia is an important key contributory factor for ischemic heart disease and is associated with age, high blood pressure, a family history of hypercholesterolemia, and diabetes. Chinese herbal medicines have been used for a long time as lipid-lowering agents.ObjectivesTo assess the effects of Chinese herbal medicines on hypercholesterolemia.Search strategyWe searched the following databases: The Cochrane Library (issue 8, 2010), MEDLINE (until July 2010), EMBASE (until July 2010 ), Chinese BioMedical Database (until July 2010), Traditional Chinese Medical Literature Analysis and Retrieval System (until July 2010), China National Knowledge Infrastructure (until July 2010), Chinese VIP Information (until July 2010), Chinese Academic Conference Papers Database and Chinese Dissertation Database (until July 2010), and Allied and Complementary Medicine Database (until July 2010).Selection criteriaWe considered randomized controlled clinical trials in hypercholesterolemic participants comparing Chinese herbal medicines with placebo, no treatment, and pharmacological or non-pharmacological interventions.Data collection and analysisTwo review authors independently extracted data and assessed the risk of bias. We resolved any disagreements with this assessment through discussion and a decision was achieved based by consensus. We assessed trials for the risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, incomplete outcome data, selective outcome reporting and other sources of bias.Main resultsWe included 22 randomized trials (2130 participants). The mean treatment duration was 2.3 ± 1.3 months (ranging from one to six months). Twenty trials were conducted in China and 18 trials were published in Chinese. Overall, the risk of bias of included trials was high or unclear. Five different herbal medicines were evaluated in the included trials, which compared herbs with conventional medicine in six comparisons (20 trials), or placebo (two trials). There were no outcome data in any of the trials on cardiovascular events and death from any cause. One trial each reported well-being (no significant differences) and economic costs. No serious adverse events were observed. Xuezhikang was the most commonly used herbal formula investigated. A significant effect on total cholesterol (two trial, 254 participants) was shown in favor of Xuezhikang when compared with inositol nicotinate (mean difference (MD) -0.90 mmol/L, 95% confidence interval (CI) -1.13 to -0.68) .Authors' conclusionsSome herbal medicines may have cholesterol-lowering effects. Our findings have to be interpreted with caution due to high or unclear risk of bias of the included trials.
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