1-Deoxy-d-xylulose 5-phosphate reductoisomerase as target for anti Toxoplasma gondii agents: crystal structure, biochemical characterization and biological evaluation of inhibitors.

Toxoplasma gondii is a widely distributed apicomplexan parasite causing toxoplasmosis, a critical health issue for immunocompromised individuals and for congenitally infected foetuses. Current treatment options are limited in number and associated with severe side effects. Thus, novel anti-toxoplasma agents need to be identified and developed. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is considered the rate-limiting enzyme in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate in the parasite, and has been previously investigated for its key role as a novel drug target in some species, encompassing Plasmodia, Mycobacteria and Escherichia coli. In this study, we present the first crystal structure of T. gondii DXR (TgDXR) in a tertiary complex with the inhibitor fosmidomycin and the cofactor NADPH in dimeric conformation at 2.5 Šresolution revealing the inhibitor binding mode. In addition, we biologically characterize reverse α-phenyl-ß-thia and ß-oxa fosmidomycin analogues and show that some derivatives are strong inhibitors of TgDXR which also, in contrast with fosmidomycin, inhibit the growth of T. gondii in vitro. Here, ((3,4-dichlorophenyl)((2-(hydroxy(methyl)amino)-2-oxoethyl)thio)methyl)phosphonic acid was identified as the most potent anti T. gondii compound. These findings will enable the future design and development of more potent anti-toxoplasma DXR inhibitors.

More Than a Decade Since the Latest CONSORT Non-inferiority Trials Extension: Do Infectious Diseases Trials Do Enough?

More than a decade after the Consolidated Standards of Reporting Trials group released a reporting items checklist for non-inferiority randomized controlled trials, the infectious diseases literature continues to underreport these items. Trialists, journals, and peer reviewers should redouble their efforts to ensure infectious diseases studies meet these minimum reporting standards.

Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity.

S100 proteins are small proteins that are only expressed in vertebrates. They are widely expressed in many different cell types and are involved in the regulation of calcium homeostasis, glucose metabolism, cell proliferation, apoptosis, inflammation and tumorigenesis. As members of the S100 protein subfamily of myeloid-related proteins, S100A8, S100A9 and S100A12 play a crucial role in resisting microbial infection and maintaining immune homeostasis. These proteins chelate the necessary metal nutrients of pathogens invading the host by means of 'nutritional immunity' and directly inhibit the growth of pathogens in the host. They interact with receptors on the cell surface to initiate inflammatory signal transduction, induce cytokine expression and participate in the inflammatory response and immune regulation. Furthermore, the increased content of these proteins during the pathological process makes them useful as disease markers for screening and detecting related diseases. This article summarizes the structure and function of the proteins S100A8, S100A9 and S100A12 and lays the foundation for further understanding their roles in infection, immunity and inflammation, as well as their potential applications in the prevention and treatment of infectious diseases.

Green synthesized silver nanoparticles from Phoenix dactylifera synergistically interact with bioactive extract of Punica granatum against bacterial virulence and biofilm development.

The global rise of antibiotic resistance poses a substantial risk to mankind, underscoring the necessity for alternative antimicrobial options. Developing novel drugs has become challenging in matching the pace at which microbial resistance is evolving. Recently, nanotechnology, coupled with natural compounds, has emerged as a promising solution to combat multidrug-resistant bacteria. In the present study, silver nanoparticles were green-synthesized using aqueous extract of Phoenix dactylifera (variety Ajwa) fruits and characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) coupled with Energy dispersive X-ray analysis (EDX), Transmission electron microscopy (TEM) and Thermogravimetric-differential thermal analysis (TGA-DTA). The in-vitro synergy of green synthesized P. dactylifera silver nanoparticle (PD-AgNPs) with selected antibiotics and bioactive extract of Punica granatum, i.e., ethyl acetate fraction (PGEF), was investigated using checkerboard assays. The most effective synergistic combination was evaluated against the QS-regulated virulence factors production and biofilm of Pseudomonas aeruginosa PAO1 by spectroscopic assays and electron microscopy. In-vivo anti-infective efficacy was examined in Caenorhabditis elegans N2 worms. PD-AgNPs were characterized as spherical in shape with an average diameter of 28.9 nm. FTIR analysis revealed the presence of functional groups responsible for the decrease and stabilization of PD-AgNPs. The signals produced by TGA-DTA analysis indicated the generation of thermally stable and pure crystallite AgNPs. Key phytocompounds detected in bioactive fractions include gulonic acid, dihydrocaffeic acid 3-O-glucuronide, and various fatty acids. The MIC of PD-AgNPs and PGEF ranged from 32 to 128 µg/mL and 250-500 µg/mL, respectively, against test bacterial strains. In-vitro, PD-AgNPs showed additive interaction with selected antibiotics (FICI 0.625-0.75) and synergy with PGEF (FICI 0.25-0.375). This combination inhibited virulence factors by up to 75 % and biofilm formation by 84.87 % in P. aeruginosa PAO1. Infected C. elegans worms with P. aeruginosa PAO1 had a 92.55 % survival rate when treated with PD-AgNPs and PGEF. The combination also reduced the reactive oxygen species (ROS) level in C. elegans N2 compared to the untreated control. Overall, these findings highlight that biosynthesized PD-AgNPs and bioactive P. granatum extract may be used as a potential therapeutic formulation against MDR bacteria.

Safety of carrageenan-based gels as preventive microbicides: a narrative review.

BACKGROUND: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use. METHODS: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use. RESULTS: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group. CONCLUSIONS: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce.

Advances in hepatitis delta research: emerging insights and future directions.

OBJECTIVES: Hepatitis delta virus (HDV) is a defective virus needing the envelope provided by hepatitis B virus (HBV) in order to enter liver cells and propagate. Chronic HDV infection is considered the most severe viral hepatitis, resulting in accelerated fibrosis progression until cirrhosis and its complications (hepatocellular carcinoma, liver decompensation) compared with HBV mono-infected patients. Off-label treatment with interferon has represented the only treatment option in the last 40 years, resulting in suboptimal virological response rates and being limited by safety issues especially in patients with advanced cirrhosis. Recently, the first HBV-HDV entry inhibitor Bulevirtide (BLV) has been approved by the European Medicines Agency (EMA) for treatment of chronic compensated HDV. METHODS: This review summarises most recent updates on HDV epidemiology, diagnosis and treatment, with a special focus both on clinical trials and real-life studies about BLV. An overview on new HDV compounds under development is also provided. RESULTS: BLV, the HBV-HDV entry inhibitor, has shown promising safety and efficacy data in clinical trials and in real-life studies, also in patients with advanced cirrhosis and portal hypertension. However, according to EMA label treatment is currently intended long-term until clinical benefit and predictors of responses are still undefined. The potential combination with PegIFNα seems to increase virological and clinical responses. New compounds are under development or in pipeline for treatment of HDV. CONCLUSION: After more than 40 years since HDV discovery, new treatment options are currently available to provide efficient strategies for chronic hepatitis Delta.

Evaluation of Pharmacokinetic and Pharmacodynamic (PK/PD) of Novel Fluorenylmethoxycarbonyl- Phenylalanine Antimicrobial Agent.

OBJECTIVE: To assess the pharmacokinetic profile, in-vivo toxicity, and efficacy of 9-Fluorenylmethoxycarbonyl-L-phenylalanine (Fmoc-F) as a potential antibacterial agent, with a focus on its suitability for clinical translation. METHODS: An RP-HPLC-based bio-analytical method was developed and qualified to quantify Fmoc-F levels in mouse plasma for pharmacokinetic analysis. Oral bioavailability was determined, and in-vivo toxicity was evaluated following intra-peritoneal administration. Efficacy was assessed by measuring the reduction in Staphylococcus aureus burden and survival rates in BALB/c mice. RESULTS: The RP-HPLC method is highly sensitive, detecting as low as 0.8 µg mL-1 (~ 2 µM) of Fmoc-F in blood plasma. This study revealed that Fmoc-F has an oral bioavailability of 65 ± 18% and suitable pharmacokinetic profile. Further, we showed that intra-peritoneal administration of Fmoc-F is well tolerated by BALB/c mice and Fmoc-F treatment (100 mg/kg, i.p.) significantly reduces Staphylococcus aureus burden from visceral organs in BALB/c mice but falls short in enhancing survival rates at higher bacterial loads. CONCLUSIONS: The study provides crucial insights into the pharmacokinetic and pharmacodynamic properties of Fmoc-F. The compound displayed favourable oral bioavailability and in-vivo tolerance. Its significant reduction of bacterial burden underscores its potential as a treatment for systemic infections. However, limited effectiveness for severe infections, short half-life, and inflammatory response at higher doses need to be addressed for its clinical application.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Quinolone scaffolds as potential drug candidates against infectious microbes: a review.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.

Pharmacogenomics and adverse effects of anti-infective drugs in children.

Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.

Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS.

INTRODUCTION: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. METHODS: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. RESULTS: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. DISCUSSION/CONCLUSION: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.

Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Association of Papacarie Duo® and low-level laser in antimicrobial photodynamic therapy (aPDT).

Dental caries is a multifactorial, non-communicable disease. Effective treatment options for minimally invasive removal of carious tissue include Papacarie Duo® gel and antimicrobial photodynamic therapy (aPDT). aPDT involves a combination of a light source and photosensitizer. Given that Papacarie Duo® contains a percentage of blue dye, this study aims to explore the antimicrobial potential of Papacarie Duo® when associated with a light source against Streptococcus mutans strains. The chosen light source was a low-power diode laser (λ = 660 nm, E = 3 J, P = 100 mW, t = 30 s). To assess antimicrobial capacity, planktonic suspensions of Streptococcus mutans were plated on Brain Heart Infusion Agar (BHI) to observe the formation of inhibition halos. The studied groups included methylene blue (0.005%), Papacarie Duo®, distilled water (negative control), 2% chlorhexidine (positive control), Papacarie Duo® + laser, and methylene blue (0.005%) + laser. Following distribution onto plates, each group was incubated at 37 °C for 48 h under microaerophilic conditions. Inhibition halos were subsequently measured using a digital caliper. The results showed that chlorhexidine had the greatest antimicrobial effect followed by the group of irradiated methylene blue and irradiated Papacarie Duo®. All experimental groups demonstrated antimicrobial potential, excluding the negative control group. The study concludes that Papacarie Duo® exhibits antimicrobial properties when associated with a low-power diode laser.

Topical pravibismane as adjunctive therapy for moderate or severe diabetic foot infections: A phase 1b randomized, multicenter, double-blind, placebo-controlled trial.

This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).

The antibiotic resistance profiles of Pseudomonas aeruginosa in the Asia Cornea Society Infectious Keratitis Study.

PURPOSE: To describe the prevalence and antibiotic resistance profiles of Pseudomonas aeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS). METHODS: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P. aeruginosa against thirteen antibiotics from 6 different classes, and categorized based on Clinical Laboratory Standard Institutes' reference ranges. The percentage rates of resistance (non-susceptibility) to each antibiotic included isolates of both intermediate and complete resistance. Multi-drug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. RESULTS: Of the 1493 unique bacterial specimens obtained from ACSIKS, 319 isolates were of P. aeruginosa. The majority of isolates were from centers in India (n = 118, 37%), Singapore (n = 90, 28.2%), Hong Kong (n = 31, 9.7%) and Thailand (n = 30, 9.4%). The cumulative antibiotic resistance rate was the greatest for polymyxin B (100%), ciprofloxacin (17.6%) and moxifloxacin (16.9%), and lowest for cefepime (11.6%) and amikacin (13.5%). Isolates from India demonstrated the highest antibiotic resistance rates of all the centers, and included moxifloxacin (47.5%) and ciprofloxacin (39.8%). Forty-eight of the 59 MDR isolates also originated from India. Antibiotic resistance rates were significantly lower in the other ACSIKS centers, and were typically less than 10%. CONCLUSIONS: The antibiotic resistance profiles of P. aeruginosa varied between different countries. While it was low for most countries, substantial antibiotic resistance and a significant number of multi-drug resistant isolates were noted in the centers from India.

Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antiretroviral Therapies: A Systematic Review.

BACKGROUND: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. METHODS: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. RESULTS: We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%). CONCLUSIONS: ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence.

Plant Antimicrobial Peptides: Insights into Structure-Function Relationships for Practical Applications.

Antimicrobial peptides (AMPs) are short polypeptide molecules produced by multicellular organisms that are involved in host defense and microbiome preservation. In recent years, AMPs have attracted attention as novel drug candidates. However, their successful use requires detailed knowledge of the mode of action and identification of the determinants of biological activity. In this review, we focused on structure-function relationships in the thionins, α-hairpinins, hevein-like peptides, and the unique Ib-AMP peptides isolated from Impatiens balsamina. We summarized the available data on the amino acid sequences and 3D structure of peptides, their biosynthesis, and their biological activity. Special attention was paid to the determination of residues that play a key role in the activity and the identification of the minimal active cores. We have shown that even subtle changes in amino acid sequences can affect the biological activity of AMPs, which opens up the possibility of creating molecules with improved properties, better therapeutic efficacy, and cheaper large-scale production.

Facile Production of the Pseudomonas aeruginosa Virulence Factor LasB in Escherichia coli for Structure-Based Drug Design.

The human pathogen Pseudomonas aeruginosa has a number of virulence factors at its disposal that play crucial roles in the progression of infection. LasB is one of the major virulence factors and exerts its effects through elastolytic and proteolytic activities aimed at dissolving connective tissue and inactivating host defense proteins. LasB is of great interest for the development of novel pathoblockers to temper the virulence, but access has thus far largely been limited to protein isolated from Pseudomonas cultures. Here, we describe a new protocol for high-level production of native LasB in Escherichia coli. We demonstrate that this facile approach is suitable for the production of mutant, thus far inaccessible LasB variants, and characterize the proteins biochemically and structurally. We expect that easy access to LasB will accelerate the development of inhibitors for this important virulence factor.

Characterization of Cetobacterium somerae CPU-CS01 isolated from the intestine of healthy crucian carp (Carassius auratus) as potential probiotics against Aeromonas hydrophila infection.

Cetobacterium somerae is a commensal bacterium for many fish species. However, research on C. somerae has been limited so far, and its function and beneficial potential require to be further investigated. The objective of this study was to evaluate the probiotic properties of C. somerae CPU-CS01 isolated from the intestinal contents of crucian carp (Carassius auratus). Hemolytic activity, antibiotic susceptibility, acid tolerance, bile salt tolerance, free radical scavenging, and enzyme production properties were tested for in vitro. Caenorhabditis elegans and zebrafish (Danio rerio) model were used to evaluate the antioxidant and anti-infective effects of C. somerae CPU-CS01 in vivo. Our results showed that C. somerae CPU-CS01 had no hemolytic activity, it produced cellulase, amylase, and survived at low pH (2.0-3.0) and in the presence of bile salts. The cell-free culture supernatant (CFCS) of C. somerae CPU-CS01 possessed DPPH radical, hydroxyl radical, and superoxide anion scavenging activity. C. elegans fed with C. somerae CPU-CS01 were more resistant to hydrogen peroxide-induced oxidative stress and Aeromonas hydrophila infection. In addition, zebrafish-fed diets containing C. somerae CPU-CS01 showed improved survival after A. hydrophila infection. Based on these results, the positive probiotic properties of C. somerae CPU-CS01 isolated from the intestinal contents of crucian carp make it a potential candidate for probiotic.

Hesperidin methyl chalcone, a citrus flavonoid, inhibits Aeromonas hydrophila infection mediated by quorum sensing.

Plant-derived phytocompounds are effective in treating a variety of ailments and disorders, the most common of which are bacterial infections in humans, which are a major public health concern. Flavonoids, one of the groups of phytocompounds, are known to have significant antimicrobial and anti-infective properties. Hence, the current study investigates the efficacy of the citrus flavonoid hesperidin methylchalcone (HMC) in addressing this major issue. The results of this study indicate that the anti-quorum sensing (anti-QS) action against Aeromonas hydrophila infections is exhibited with a decrease in biofilm development and virulence factors production through in vitro and in silico analyses. In addition, the qPCR findings indicate that HMC has antivirulence action on A. hydrophila by reducing the expression of QS-related virulence genes, including ahyR, ahyB, ahh1, aerA, and lip. Interestingly, HMC significantly rescued the A. hydrophila-infected zebrafish by reducing the internal colonization, demonstrating the in vivo anti-infective potential of HMC against A. hydrophila infection. Based on these results, this study recommends that HMC could be employed as a possible therapeutic agent to treat A. hydrophila-related infections in humans.