[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Anti-Biofilm Activity of Assamsaponin A, Theasaponin E1, and Theasaponin E2 against Candida albicans.

Biofilm formation plays a crucial role in the pathogenesis of Candida albicans and is significantly associated with resistance to antifungal agents. Tea seed saponins, a class of non-ionic triterpenes, have been proven to have fungicidal effects on planktonic C. albicans. However, their anti-biofilm activity and mechanism of action against C. albicans remain unclear. In this study, the effects of three Camellia sinensis seed saponin monomers, namely, theasaponin E1 (TE1), theasaponin E2 (TE2), and assamsaponin A (ASA), on the metabolism, biofilm development, and expression of the virulence genes of C. albicans were evaluated. The results of the XTT reduction assay and crystal violet (CV) staining assay demonstrated that tea seed saponin monomers concentration-dependently suppressed the adhesion and biofilm formation of C. albicans and were able to eradicate mature biofilms. The compounds were in the following order in terms of their inhibitory effects: ASA > TE1 > TE2. The mechanisms were associated with reductions in multiple crucial virulence factors, including cell surface hydrophobicity (CSH), adhesion ability, hyphal morphology conversion, and phospholipase activity. It was further demonstrated through qRT-PCR analysis that the anti-biofilm activity of ASA and TE1 against C. albicans was attributed to the inhibition of RAS1 activation, which consequently suppressed the cAMP-PKA and MAPK signaling pathways. Conversely, TE2 appeared to regulate the morphological turnover and hyphal growth of C. albicans via a pathway that was independent of RAS1. These findings suggest that tea seed saponin monomers are promising innovative agents against C. albicans.

The Efficiency of Erbium Lasers in the Removal of Root Canal System and Surface Biofilms: A Systematic Review and Meta-Analysis.

Background: Studies have shown positive effects of erbium lasers in removal of biofilms. A review article was required with quantitative data for confirmation of their effects, but there is still no a comprehensive study reviewing their effects based on the root canal and implant surface. This systematic review and meta-analysis was conducted to evaluate the efficiency of erbium lasers in removal of the root canal system and surface biofilms. Methods: Studies were searched with keywords in databases of PubMed, Scopus, Europe PMC, Cochrane Central, Embase, and Web of Science and screened by referees. Data were included based on mean ± standard deviation and size of control and laser groups. Effect sizes were assessed as standardized mean differences and calculated for each study and for the root and dental surface. Laser characteristics and bacteria were considered as moderators. Results: Nineteen articles in the current study comprised 565 samples (283 control samples and 282 laser samples). The analyses showed the significant effects of erbium lasers on bacterial biofilms on the implant surface [-0.496, 95% confidence interval, CI (-0.720 to -0.273); I2 = 26.94; p = 0.029; Q = 13.28] and root canal [-0.551, 95% CI (-0.656 to -0.445); I2 = 23.89; p = 0.031; Q = 10.46]. Results showed that highest efficiency lasers were obtained at higher wavelengths of 2940 nm, 75-100 mJ energy, and 100-150 µsec and <50-Hz pulses. Conclusions: Erbium lasers can be used to remove biofilms on dental implant surfaces and root canal systems and are safe options for untouchable sites in the root canal.

Antibacterial effect of Moringa oleifera on Staphylococcus aureus and Pseudomonas aeruginosa isolated from raw milk and some dairy products with special reference to biofilm gene expression.

Background: Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) are well defined as food poisoning pathogens that are highly resistant and need continuous studies. Aim: The purpose of the work was to examine phenotypic and genotypic characteristics of both P. aeruginosa and S. aureus, and treatment trials with medicinal plants. Methods: Samples were examined for isolation of P. aeruginosa and S. aureus on selective media followed by biochemical confirmation, biofilm formation, genes detection, and expression of P. aeruginosa pslA biofilm gene was performed by quantitative real-time polymerase chain reaction after treatment with 0.312 mg/ml Moringa oleifera aqueous extract as a minimum inhibitory concentration. Results: The highest isolation rate of P. aeruginosa was 20% from both raw milk and Kariesh cheese, followed by 16% and 12% from ice cream and processed cheese, respectively, while the highest isolation rate of S. aureus was 36% from raw milk followed by 28% in ice cream and 16% in both Kariesh cheese and processed cheese. 30% of P. aeruginosa isolates were biofilm producers, while only 21% of S. aureus isolates were able to produce biofilm. The P. aeruginosa isolates harbor virulence-associated genes nan1, exoS, toxA, and pslA at 100%, 80%, 40%, and 40%, respectively. Staphylococcus aureus SEs genes were examined in S. aureus strains, where SEA and SEB genes were detected with 60%, but no isolate harbored SEC, SED, or SEE. The significant fold change of P. aeruginosa pslA expression was 0.40332 after treatment with M. oleifera aqueous extract. Conclusion: Pseudomonas aeruginosa and S. aureus harbor dangerous virulence genes that cause food poisoning, but M. oleifera extract could minimize their action.

Study on the inhibition activity and mechanism of Tanreqing against Klebsiella pneumoniae biofilm formation in vitro and in vivo.

Objective: To evaluate the antibacterial effect of Tanreqing (TRQ) against K. pneumoniae and its inhibition activity on bacterial biofilm formation in vitro and in vivo, and to explore the mechanism of the inhibitory effects of TRQ on K. pneumoniae biofilm formation. Methods: An in vitro biofilm model of K. pneumoniae was established, and the impact of TRQ on biofilm formation was evaluated using crystal violet staining and scanning electron microscopy (SEM). Furthermore, the clearance effect of TRQ against K. pneumoniae in the biofilm was assessed using the viable plate counting method; q-RT PCR was used to evaluate the inhibitory effect of different concentrations of TRQ on the expression of biofilm-related genes in Klebsiella pneumoniae; The activity of quorum sensing signal molecule AI-2 was detected by Vibrio harveyi bioluminescence assay; Meanwhile, a guinea pig lung infection model of Klebsiella pneumoniae was constructed, and after treated with drugs, pathological analysis of lung tissue and determination of bacterial load in lung tissue were performed. The treatment groups included TRQ group, imipenem(IPM) group, TRQ+IPM group, and sterile saline group as the control. Results: The formation of K. pneumoniae biofilm was significantly inhibited by TRQ in vitro experiments. Furthermore, when combined with IPM, the clearance of K. pneumoniae in the biofilm was notably increased compared to the TRQ group and IPM group alone. q-RT PCR analysis revealed that TRQ down-regulated the expression of genes related to biofilm formation in K. pneumoniae, specifically luxS, wbbm, wzm, and lsrK, and also inhibited the activity of AI-2 molecules in the bacterium. In vivo experiments demonstrated that TRQ effectively treated guinea pig lung infections, resulting in reduced lung inflammation. Additionally, when combined with IPM, there was a significant reduction in the bacterial load in lung tissue. Conclusion: TRQ as a potential therapeutic agent plays a great role in the treatment of K. pneumoniae infections, particularly in combination with conventional antibiotics. And TRQ can enhanced the clearance effect on the bacterium by inhibiting the K. pneumoniae biofilm formation, which provided experimental evidence in support of clinical treatment of TRQ against K. pneumoniae infections.

Phytochemical screening of Podocarpus lambertii Klotzch ex Endl. leaf extracts and potential antimicrobial, antioxidant and antibiofilm activity.

Species of the genus Podocarpus L'Hér. ex Pers.present biological activities, such as analgesic, antioxidant, antifungal, acting in the fight against anemia, depurative and fortifying. Podocarpus lambertii Klotzch ex Endl. is a Brazilian native species popularly known as maritime pine and lacks information about its phytochemical profile and possible biological activities. The study was conducted to determine the phytochemical composition of soluble plant extracts of acetone (EA), ethyl acetate (EAE) and hexane (HE) from leaves of P. lambertii; evaluate the antimicrobial potential by the broth microdilution technique; antioxidant potential by the DPPH method, as well as to evaluate the biofilm inhibition capacity by the crystal violet assay and reduction of the yellow tetrazolium salt (MTT). Phytochemical screening detected the presence of flavonoids, triterpenoids, steroids, tannins, alkaloids and saponins. All extracts showed antimicrobial activity on the microorganisms tested, and the EA showed the best results. High free radical scavenging potential was observed only in EAE (96.35%). The antibiofilm potential was observed in the EAE extract. The results contribute to the knowledge of the species and indicate the potential of P. lambertii extracts as a source of plant bioactives for the development of new alternative strategies to control resistant microorganisms.

Inadvertently enriched cyanobacteria prompted bacterial phosphorus uptake without aeration in a conventional anaerobic/oxic reactor.

The enhanced biological phosphorus removal (EBPR) process requires alternate anaerobic and aerobic conditions, which are regulated respectively by aeration off and on. Recently, in an ordinary EBPR reactor, an abnormal orthophosphate concentration (PO43--P) decline in the anaerobic stage (namely non-aerated phosphorus uptake) aroused attention. It was not occasionally but occurred in each cycle and lasted for 101 d and shared about 16.63 % in the total P uptake amount. After excluding bio-mineralization and surface re-aeration, indoor light conditions (180 to 260 lx) inducing non-aerated P uptake were confirmed. High-throughput sequencing analysis revealed that cyanobacteria could produce oxygen via photosynthesis and were inhabited inside wall biofilm. The cyanobacteria (Pantalinema and Leptolyngbya ANT.L52.2) were incubated in a feeding transparent silicone hose, entered the reactor along with influent, and outcompeted Chlorophyta, which existed in the inoculum. Eventually, this work deciphered the reason for non-aerated phosphorus uptake and indicated its potential application in reducing CO2 emissions and energy consumption via the cooperation of microalgal-bacterial and biofilm-sludge.

Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

1,25 dihydroxyvitamin D3-mediated effects on bovine innate immunity and on biofilm-forming Staphylococcus spp. isolated from cattle with mastitis.

Mastitis is one the most widespread and serious diseases in dairy cattle. Recurrent and chronic infections are often attributable to certain pathogenicity mechanisms in mastitis-causing pathogens such as Staphylococcus spp. These include growing in biofilm and invading cells, both of which make it possible to resist or evade antimicrobial therapies and the host's immune system. This study tested the effects of active vitamin D3 (i.e., calcitriol or 1,25-dihydroxyvitamin D3) on the internalization and phagocytosis of biofilm-forming Staphylococcus spp. isolated from animals with mastitis. Two established bovine cell lines were used: MAC-T (mammary epithelial cells) and BoMac (macrophages). Calcitriol (0-200 nM) did not affect the viability of MAC-T cells nor that of BoMac cells after 24 and 72 h. Concentrations of 0-100 mM for 24 h upregulated the expression of 24-hydroxylase in MAC-T cells, but did not alter that of VDR. Pre-treatment of the cells with calcitriol for 24 h decreased the internalization of S. aureus V329 into MAC-T cells (0-100 nM), and stimulated the phagocytosis of the same strain and of S. xylosus 4913 (0-10 nM). Calcitriol and two conditioned media, obtained by treating the cells with 25-200 nM of the metabolite for 24 h, were also assessed in terms of their antimicrobial and antibiofilm activity. Neither calcitriol by itself nor the conditioned media affected staphylococcal growth or biofilm formation (0-200 nM for 12 and 24 h, respectively). In contrast, the conditioned media (0-100 nM for 24 h) decreased the biomass of preformed non-aureus staphylococcal biofilms and killed the bacteria within them, without affecting metabolic activity. These effects may be mediated by reactive oxygen species and proteins with antimicrobial and/or antibiofilm activity. In short, calcitriol could make pathogens more accessible to antimicrobial therapies and enhance bacterial clearance by professional phagocytes. Moreover, it may modulate the host's endogenous defenses in the bovine udder and help combat preformed non-aureus staphylococcal biofilms (S. chromogenes 40, S. xylosus 4913, and/or S. haemolyticus 6). The findings confirm calcitriol's potential as an adjuvant to prevent and/or treat intramammary infections caused by Staphylococcus spp., which would in turn contribute to reducing antibiotic use on dairy farms.

Unraveling the significance of calcium as a biofilm promotion signal for Bacillus licheniformis strains isolated from dairy products.

Bacillus licheniformis, a quick and strong biofilm former, is served as a persistent microbial contamination in the dairy industry. Its biofilm formation process is usually regulated by environmental factors including the divalent cation Ca2+. This work aims to investigate how different concentrations of Ca2+ change biofilm-related phenotypes (bacterial motility, biofilm-forming capacity, biofilm structures, and EPS production) of dairy B. licheniformis strains. The Ca2+ ions dependent regulation mechanism for B. licheniformis biofilm formation was further investigated by RNA-sequencing analysis. Results revealed that supplementation of Ca2+ increased B. licheniformis biofilm formation in a dose-dependent way, and enhanced average coverage and thickness of biofilms with complex structures were observed by confocal laser scanning microscopy. Bacterial mobility of B. licheniformis was increased by the supplementation of Ca2+ except the swarming ability at 20 mM of Ca2+. The addition of Ca2+ decreased the contents of polysaccharides but promoted proteins production in EPS, and the ratio of proteins/polysaccharides content was significantly enhanced with increasing Ca2+ concentrations. RNA-sequencing results clearly indicated the variation in regulating biofilm formation under different Ca2+ concentrations, as 939 (671 upregulated and 268 downregulated) and 951 genes (581 upregulated and 370 downregulated) in B. licheniformis BL2-11 were induced by 10 and 20 mM of Ca2+, respectively. Differential genes were annotated in various KEGG pathways, including flagellar assembly, two-component system, quorum sensing, ABC transporters, and related carbohydrate and amino acid metabolism pathways. Collectively, the results unravel the significance of Ca2+ as a biofilm-promoting signal for B. licheniformis in the dairy industry.

Green fabrication of ZnO nanoparticles via spirulina platensis and its efficiency against biofilm forming pathogens.

Excessive consumption of antibiotics is considered one of the top public health threats, this necessitates the development of new compounds that can hamper the spread of infections. A facile green technology for the biosynthesis of Zinc oxide nanoparticles (ZnO NPs) using the methanol extract of Spirulina platensis as a reducing and stabilizing agent has been developed. A bunch of spectroscopic and microscopic investigations confirmed the biogenic generation of nano-scaled ZnO with a mean size of 19.103 ± 5.66 nm. The prepared ZnO NPs were scrutinized for their antibacterial and antibiofilm potentiality, the inhibition zone diameters ranged from 12.57 ± 0.006 mm to 17.33 ± 0.006 mm (at 20 µg/mL) for a variety of Gram-positive and Gram-negative pathogens, also significant eradication of the biofilms formed by Staphylococcus aureus and Klebsiella pneumoniae by 96.7% and 94.8% respectively was detected. The free radical scavenging test showed a promising antioxidant capacity of the biogenic ZnO NPs (IC50=78.35 µg/mL). Furthermore, the anti-inflammatory role detected using the HRBCs-MSM technique revealed an efficient stabilization of red blood cells in a concentration-dependent manner. In addition, the biogenic ZnO NPs have significant anticoagulant and antitumor activities as well as minimal cytotoxicity against Vero cells. Thus, this study offered green ZnO NPs that can act as a secure substitute for synthetic antimicrobials and could be applied in numerous biomedical applications.

In vitro antimicrobial and antibiofilm screening of eighteen Iranian medicinal plants.

BACKGROUND: Natural products are one of the best candidates for controlling drug-resistant pathogens, the advantages of which include low production costs and low side effects. In this study, as potential antimicrobials, the anti-bacterial and antibiofilm activities of several Iranian native medicinal plants were screened. METHODS: The antibacterial/antifungal and anti-biofilm activities of 18 medicinal plants including Reseda lutea L., Nepeta sintenisii Bunge., Stachys turcomanica Trautv., Stachys lavandulifolia Vahl, Diarthron antoninae (Pobed.) Kit Tan., Ziziphora clinopodioides Lam., Euphorbia kopetdaghi Prokh, Euphorbia serpens Kunth., Hymenocrater calycinus Benth., Scutellaria pinnatifida A.Ham., Viola tricolor L., Hypericum helianthemoides (Spach) Boiss., Hypericum scabrum L., Convolvulus lineatus L., Scabiosa rotata M.Bieb Greuter & Burdet, Delphinium semibarbatum Bien. Ex Boiss., Glycyrrhiza triphylla Fisch. & C.A.Mey., and Ziziphus jujuba Mill., against two Gram-positive bacteria, Staphylococcus aureus, Bacillus cereus, as well as two Gram-negative bacteria, Pseudomonas aeruginosa, Escherichia coli; and Candida albicans as a fungal strain, were evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values of the extracts against tested microorganisms were reported and we investigated their effect on the biofilm inhibition of Pseudomonas aeruginosa PAO1, Staphylococcus epidermis, Staphylococcus aureus and Streptococcus mutans. In addition, the effect of the extracts on the eradication of the biofilms of these bacteria was evaluated. RESULTS: In this study, H. scabrum was found to exhibit potentially significant activity against Gram-positive bacteria with the MIC range of 6.25-25 µg/mL. This extract also showed a significant effect on inhibiting the biofilm of S. aureus, S. mutans, and S. epidermidis and eradicating the biofilm of S. epidermidis DSMZ 3270. In addition, Hymenocrater calycinus root extract had moderate antibacterial activity against B. cereus with the MIC and MBC 62.5 µg/mL, respectively. CONCLUSIONS: The results of this study showed that the root extracts of two plants, Hypericum scabrum and Hymenocrater calycinus, had antimicrobial and anti-biofilm effects. Based on the observed anti-biofilm effects, these two plants may be considered in future studies to find responsible antimicrobial compounds.

Biological activity of silver nanoparticles synthesized using viticultural waste.

This research paper presents a novel approach to the green synthesis of silver nanoparticles (AgNPs) using viticultural waste, allowing to obtain NP dispersions with distinct properties and morphologies (monodisperse and polydisperse AgNPs, referred to as mAgNPs and pAgNPs) and to compare their biological activities. Our synthesis method utilized the ethanolic extract of Vitis vinifera pruning residues, resulting in the production of mAgNPs and pAgNPs with average sizes of 12 ± 5 nm and 19 ± 14 nm, respectively. Both these AgNPs preparations demonstrated an exceptional stability in terms of size distribution, which was maintained for one year. Antimicrobial testing revealed that both types of AgNPs inhibited either the growth of planktonic cells or the metabolic activity of biofilm sessile cells in Gram-negative bacteria and yeasts. No comparable activity was found towards Gram-positives. Overall, pAgNPs exhibited a higher antimicrobial efficacy compared to their monodisperse counterparts, suggesting that their size and shape may provide a broader spectrum of interactions with target cells. Both AgNP preparations showed no cytotoxicity towards a human keratinocyte cell line. Furthermore, in vivo tests using a silkworm animal model indicated the biocompatibility of the phytosynthesized AgNPs, as they had no adverse effects on insect larvae viability. These findings emphasize the potential of targeted AgNPs synthesized from viticultural waste as environmentally friendly antimicrobial agents with minimal impact on higher organisms.

Regulation and mechanism of organic selenium on quorum sensing, biofilm, and antioxidant effects of Lactobacillus paracasei.

Different organic compounds can have varying degrees of impact on the activity of Lactobacillus paracasei. The study focused on the impact and action mechanism of different organic selenium products on the bioactivity of two strains of L. paracasei. The growth, antioxidant activity, extracellular polysaccharide secretion, quorum sensing (QS), and biofilm formation of the strains before and after the addition of organic selenium crude products and three organic selenium standard were evaluated. The results showed that the addition of crude organic selenium promoted the various activities of the strain. l-selenocysteine had the strongest regulatory effect, with maximum GIM1.80 biofilm formation when it reached a critical concentration of 0.4 µg/mL; l-selenomethionine resulted in the highest activity of the signal molecule Auto inducer-2 of GDMCC1.155, when it reached a critical concentration of 0.4 µg/mL. The results of scanning electron microscopy demonstrated that the addition of organic selenium effectively improved the morphological structure of the two bacterial cells. Molecular docking revealed that the mechanism by which organic selenium regulates QS in Lactobacillus was achieved by binding two crucial receptor proteins (histidine protein kinase HKP and periplasmic binding protein LuxP) from specific sites. Furthermore, organic selenium products have a beneficial regulatory effect on the biological activity of L. paracasei. Overall, these findings provide a new alternative (organic selenium) for regulating the viability and beneficial activity of L. paracasei.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

Ginkgo biloba L. exocarp petroleum ether extract inhibits methicillin-resistant Staphylococcus aureus by modulating ion transport, virulence, and biofilm formation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.

Relationship between biofilm formation and antibiotic resistance of Klebsiella pneumoniae and updates on antibiofilm therapeutic strategies.

Klebsiella pneumoniae is a Gram-negative bacterium within the Enterobacteriaceae family that can cause multiple systemic infections, such as respiratory, blood, liver abscesses and urinary systems. Antibiotic resistance is a global health threat and K. pneumoniae warrants special attention due to its resistance to most modern day antibiotics. Biofilm formation is a critical obstruction that enhances the antibiotic resistance of K. pneumoniae. However, knowledge on the molecular mechanisms of biofilm formation and its relation with antibiotic resistance in K. pneumoniae is limited. Understanding the molecular mechanisms of biofilm formation and its correlation with antibiotic resistance is crucial for providing insight for the design of new drugs to control and treat biofilm-related infections. In this review, we summarize recent advances in genes contributing to the biofilm formation of K. pneumoniae, new progress on the relationship between biofilm formation and antibiotic resistance, and new therapeutic strategies targeting biofilms. Finally, we discuss future research directions that target biofilm formation and antibiotic resistance of this priority pathogen.

Anticandida and antibiofilm activities of extract from Schinopsis brasiliensis Engl. against Candida spp.

The pathogenic nature of infections caused by Candida spp. underscores the necessity for novel therapeutic agents. Extracts of Schinopsis brasilienses Engl are \ a promising source of agents with antifungal effects. This study aimed to assess the antifungal potential of the leaf extract of S. brasilienses. The antifungal activity was evaluated by determining the minimum inhibitory concentrations and fungicide concentrations (MIC and MFC). The antibiofilm potential was assessed by counting colony-forming units/mL. The study examined the inhibition kinetics of fungal growth and potential synergism between gallic acid or the extract and nystatin using the Checkerboard method. Cytotoxicity was evaluated through the MTT assay. The extract exhibited antifungal effect against all tested strains, with MIC and MFC ranging from 31.25-250 µg/mL. Gallic acid, the main isolated compound, displayed a MIC of 2000 µg/mL. The extract of S. brasilienses at 31.25 µg/mL inhibited the formation of biofilm by C. albicans and significantly reduced the mass of mature biofilm after 24 and 48 h (p < 0. 05). At a concentration of 125 µg/mL, the extract demonstrated significant inhibition of fungal growth after 6 hours. The combination of gallic acid or extract with nystatin did not exhibit synergistic or antagonistic effect. Furthermore, the extract did not induce cytotoxicity to a human cell line. The extract of S. brasiliensis demonstrates antifungal activity against Candida, generally exhibiting fungicidal action and capacity to inhibit biofilm formation as well as reduce mature biofilms. Additionally, the extract showed low cytotoxicity to human cells.

Design of a Novel Lysine Isopeptide 1018KI11 with Potent Antimicrobial Activity as a Safe and Stable Food Preservative Candidate.

Antimicrobial peptides are potent food additive candidates, but most of them are sensitive to proteases, which limits their application. Therefore, we substituted arginine for lysine and introduced a lysine isopeptide bond to peptide IDR-1018 in order to improve its enzymatic stability. Subsequently, the protease stability and antimicrobial/antibiofilm activity of the novel peptides (1018K2-1018KI11) were investigated. The data revealed that the antienzymatic potential of 1018KI11 to bromelain and papain increased by 2-8 folds and 16 folds, respectively. The minimum inhibitory concentration (MIC) of 1018KI11 against methicillin-resistant Staphylococcus aureus (MRSA) ATCC43300 and Escherichia coli (E. coli) ATCC25922 was reduced 2-fold compared to 1018K11. Mechanism exploration suggested that 1018KI11 was more effective than 1018K11 in disrupting the cell barrier and damaging genomic DNA. Additionally, 1018KI11 at certain concentration conditions (2-64 µg/mL) reduced biofilm development of MRSA ATCC43300 by 4.9-85.9%. These data indicated that novel peptide 1018KI11 is a potential food preservative candidate.