Gut commensal Kineothrix alysoides mitigates liver dysfunction by restoring lipid metabolism and gut microbial balance.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease, is a widespread liver condition characterized by excessive fat buildup in hepatocytes without significant alcohol consumption. Manipulation of the gut microbiome has been considered to prevent and improve the occurrence and progression of MASLD, particularly through the gut-liver axis. This study aimed to investigate the correlation between the gut microbiome and liver function and determine whether the gut microbiome can ameliorate MASLD. We comparatively analyzed the gut microbiome composition between mice fed normal chow and those fed a high-fat diet and observed that the abundance of Kineothrix alysoides decreased in the high-fat group. Further analysis showed that treatment with K. alysoides in the high-fat diet group led to decreased weight loss, and MASLD attenuation. Importantly, K. alysoides treatment attenuated MASLD in mice fed a high-fat, high-fructose diet (HFHF), which can cause advanced liver damage. Furthermore, administration of K. alysoides altered the gut microbial composition in the HFHF diet group and improved MASLD. Overall, these findings demonstrate the potential of K. alysoides in restoring gut health and facilitating lipid metabolism to prevent and treat MASLD.

An Escherichia coli strain with extra catalase activity protects against murine colitis by scavenging hydrogen peroxide and regulating regulatory t cell/interleukin-17 pathways.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract whose occurrence is attributed to various factors, including genetic factors, immune response, microbial changes, and oxidative stress. Microbial-targeted therapy has emerged as an alternative to immunosuppressive therapy for IBD. METHODS: The effects of an atypical commensal Escherichia coli strain harboring an additional catalase gene (compared to typical E. coli strain) on dextran sulfate sodium (DSS)-induced colitis were explored in mice. RESULTS: The atypical E. coli (atEc) significantly restored body weight, reduced disease activity score, and improved histological scores in mice with colitis. Hydrogen peroxide levels in colitis mice were noticeably decreased when the mice were administered atEc. The proinflammatory cytokine levels were decreased and regulatory T cell numbers were increased after the administration of atEc. The abundance of Firmicutes was significantly recovered, while that of Proteobacteria decreased in atEc -treated mice compared with that in vehicle-treated wild-type mice. To investigate the role of interleukin (IL)-17A in mediating the anti-inflammatory effects of the atEc, IL-17A‒knockout mice were orally administered atEc. Clinical and immune responses and microbial composition were significantly reduced in IL-17A‒knockout mice compared with those in wild-type mice. CONCLUSIONS: atEc ameliorates colonic inflammation by controlling hydrogen peroxide levels, immune responses (including regulatory T cells and IL-17A), and microbial composition. atEc could be a novel candidate of probiotic for IBD treatment.

An efficient system for intestinal on-site butyrate production using novel microbiome-derived esterases.

Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned E. coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine.

Molecular characteristics of fluoroquinolone-resistant avian pathogenic Escherichia coli isolated from broiler chickens.

Avian pathogenic Escherichia coli (APEC) is a major pathogen in the poultry industry worldwide including Korea. In this study, the phenotypic and genotypic characteristics of 33 fluoroquinolone (FQ)-resistant APEC isolates from broilers were analyzed. All FQ-resistant APEC isolates showed amino acid exchanges at both gyrA and parC and high minimal inhibitory concentrations for FQs. A total of 11 (33.3%) isolates were positive for the plasmid-mediated quinolone resistance (PMQR) genes, qnrA (8 isolates) and qnrS (3 isolates), and showed multidrug resistance. Among the 11 PMQR-positive isolates, 1 and 2 isolates carried blaCTX-1 and blaCTX-15, respectively, as extended-spectrum ß-lactamase (ESBL) producers, and the non-ESBL gene, blaTEM-1, was found in 4 isolates. Among 3 aminoglycoside-resistant isolates, aac(3)-II was only detected in 1 isolate. All 8 APEC isolates with resistance to tetracycline carried the tetA gene. Overall, 6 of the 7 trimethoprim-sulfamethoxazole-resistant isolates carried the sul1 or sul2 genes, while only 2 of the 8 chloramphenicol-resistant isolates carried the catA1 gene. Although 9 isolates carried class I integrons, only 4 isolates carried the gene cassettes dfrA12-aadA2 (2 isolates), dfrA17-aadA5 (1 isolate), extX-psp-aadA2 (1 isolate), and dfrA27 (1 isolate). The most common plasmid replicon was FIB (8 isolates, 72.7%), followed by K/B (4 isolates, 36.4%). Antimicrobial resistance monitoring and molecular analysis of APEC should be performed continuously to surveil the transmission between poultry farms.

Molecular characterization of avian pathogenic Escherichia coli from broiler chickens with colibacillosis.

Avian pathogenic Escherichia coli (APEC) causes extensive mortality in poultry flocks, leading to extensive economic losses. The aim of this study was to investigate the phenotypic and genotypic characteristics and antimicrobial resistance of recent APEC isolates. Of the 79 APEC isolates, the most predominant serogroup was O78 (16 isolates, 20.3%), followed by O2 (7 isolates, 8.9%) and O53 (7 isolates, 8.9%). Thirty-seven (46.8%) and six (7.6%) of the isolates belonged to phylogenetic groups D and B2, respectively, and presented as virulent extraintestinal E. coli. Among 5 analyzed virulence genes, the highest frequency was observed in hlyF (74 isolates, 93.7%), followed by iutA (72 isolates, 91.9%) gene. The distribution of the iss gene was significantly different between groups A/B1 and B2/D (P < 0.05). All group B2 isolates carried all 5 virulence genes. APEC isolates showed high resistance to ampicillin (83.5%), nalidixic acid (65.8%), tetracycline (64.6%), cephalothin (46.8%), and ciprofloxacin (46.8%). The ß-lactamases-encoding genes blaTEM-1 (23 isolates, 29.1%), blaCTX-M-1 (4 isolates, 5.1%), and blaCTX-M-15 (3 isolates, 3.8%); the aminoglycoside-modifying enzyme gene aac(3)-II (4 isolates, 5.1%); and the plasmid-mediated quinolone genes qnrA (10 isolates, 12.7%) and qnrS (2 isolates, 2.5%) were identified in APEC isolates. The tetA (37 isolates, 46.8%) and sul2 (20 isolates, 25.3%) were the most prevalent among tetracycline and sulfonamide resistant isolates, respectively. This study indicates that APEC isolates harbor a variety of virulence and resistance genes; such genes are often associated with plasmids that facilitate their transmission between bacteria and should be continuously monitored to track APEC transmission in poultry farms.

Commensal-derived metabolites govern Vibrio cholerae pathogenesis in host intestine.

BACKGROUND: Recent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels. RESULTS: Here, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice. CONCLUSIONS: Overall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.

Disruption of the Gut Ecosystem by Antibiotics.

The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.

Diffusible and Volatile Antifungal Compounds Produced by an Antagonistic Bacillus velezensis G341 against Various Phytopathogenic Fungi.

The aim of this study was to identify volatile and agar-diffusible antifungal metabolites produced by Bacillus sp. G341 with strong antifungal activity against various phytopathogenic fungi. Strain G341 isolated from four-year-old roots of Korean ginseng with rot symptoms was identified as Bacillus velezensis based on 16S rDNA and gyrA sequences. Strain G341 inhibited mycelial growth of all phytopathogenic fungi tested. In vivo experiment results revealed that n-butanol extract of fermentation broth effectively controlled the development of rice sheath blight, tomato gray mold, tomato late blight, wheat leaf rust, barley powdery mildew, and red pepper anthracnose. Two antifungal compounds were isolated from strain G341 and identified as bacillomycin L and fengycin A by MS/MS analysis. Moreover, volatile compounds emitted from strain G341 were found to be able to inhibit mycelial growth of various phytopathogenic fungi. Based on volatile compound profiles of strain G341 obtained through headspace collection and analysis on GC-MS, dimethylsulfoxide, 1-butanol, and 3-hydroxy-2-butanone (acetoin) were identified. Taken together, these results suggest that B. valezensis G341 can be used as a biocontrol agent for various plant diseases caused by phytopathogenic fungi.

A single gene of a commensal microbe affects host susceptibility to enteric infection.

Indigenous microbes inside the host intestine maintain a complex self-regulating community. The mechanisms by which gut microbes interact with intestinal pathogens remain largely unknown. Here we identify a commensal Escherichia coli strain whose expansion predisposes mice to infection by Vibrio cholerae, a human pathogen. We refer to this strain as 'atypical' E. coli (atEc) because of its inability to ferment lactose. The atEc strain is resistant to reactive oxygen species (ROS) and proliferates extensively in antibiotic-treated adult mice. V. cholerae infection is more severe in neonatal mice transplanted with atEc compared with those transplanted with a typical E. coli strain. Intestinal ROS levels are decreased in atEc-transplanted mice, favouring proliferation of ROS-sensitive V. cholerae. An atEc mutant defective in ROS degradation fails to facilitate V. cholerae infection when transplanted, suggesting that host infection susceptibility can be regulated by a single gene product of one particular commensal species.

Protective role of gut commensal microbes against intestinal infections.

The human gastrointestinal tract is colonized by multitudes of microorganisms that exert beneficial effects on human health. Mounting evidence suggests that intestinal microbiota contributes to host resistance against enteropathogenic bacterial infection. However, molecular details that account for such an important role has just begun to be understood. The commensal microbes in the intestine regulate gut homeostasis through activating the development of host innate immunity and producing molecules with antimicrobial activities that directly inhibit propagation of pathogenic bacteria. Understanding the protective roles of gut microbiota will provide a better insight into the molecular basis that underlies complicated interaction among host-pathogen-symbiont. In this review, we highlighted recent findings that help us broaden our knowledge of the intestinal ecosystem and thereby come up with a better strategy for combating enteropathogenic infection.

Cholera toxin production during anaerobic trimethylamine N-oxide respiration is mediated by stringent response in Vibrio cholerae.

As a facultative anaerobe, Vibrio cholerae can grow by anaerobic respiration. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly promoted during anaerobic growth using trimethylamine N-oxide (TMAO) as an alternative electron acceptor. Here, we investigated the molecular mechanisms of TMAO-stimulated CT production and uncovered the crucial involvement of stringent response in this process. V. cholerae 7th pandemic strain N16961 produced a significantly elevated level of ppGpp, the bacterial stringent response alarmone, during anaerobic TMAO respiration. Bacterial viability was impaired, and DNA replication was also affected under the same growth condition, further suggesting that stringent response is induced. A ΔrelA ΔspoT ppGpp overproducer strain produced an enhanced level of CT, whereas anaerobic growth via TMAO respiration was severely inhibited. In contrast, a ppGpp-null strain (ΔrelA ΔspoT ΔrelV) grew substantially better, but produced no CT, suggesting that CT production and bacterial growth are inversely regulated in response to ppGpp accumulation. Bacterial capability to produce CT was completely lost when the dksA gene, which encodes a protein that works cooperatively with ppGpp, was deleted. In the ΔdksA mutant, stringent response growth inhibition was alleviated, further supporting the inverse regulation of CT production and anaerobic growth. In vivo virulence of ΔrelA ΔspoT ΔrelV or ΔdksA mutants was significantly attenuated. The ΔrelA ΔspoT mutant maintained virulence when infected with exogenous TMAO despite its defective growth. Together, our results reveal that stringent response is activated under TMAO-stimulated anaerobic growth, and it regulates CT production in a growth-dependent manner in V. cholerae.

Functional screening of a metagenomic library reveals operons responsible for enhanced intestinal colonization by gut commensal microbes.

Evidence suggests that gut microbes colonize the mammalian intestine through propagation as an adhesive microbial community. A bacterial artificial chromosome (BAC) library of murine bowel microbiota DNA in the surrogate host Escherichia coli DH10B was screened for enhanced adherence capability. Two out of 5,472 DH10B clones, 10G6 and 25G1, exhibited enhanced capabilities to adhere to inanimate surfaces in functional screens. DNA segments inserted into the 10G6 and 25G1 clones were 52 and 41 kb and included 47 and 41 protein-coding open reading frames (ORFs), respectively. DNA sequence alignments, tetranucleotide frequency, and codon usage analysis strongly suggest that these two DNA fragments are derived from species belonging to the genus Bacteroides. Consistent with this finding, a large portion of the predicted gene products were highly homologous to those of Bacteroides spp. Transposon mutagenesis and subsequent experiments that involved heterologous expression identified two operons associated with enhanced adherence. E. coli strains transformed with the 10a or 25b operon adhered to the surface of intestinal epithelium and colonized the mouse intestine more vigorously than did the control strain. This study has revealed the genetic determinants of unknown commensals (probably resembling Bacteroides species) that enhance the ability of the bacteria to colonize the murine bowel.

Recent trends in studies on botanical fungicides in agriculture.

Plants are attacked by various phytopathogenic fungi. For many years, synthetic fungicides have been used to control plant diseases. Although synthetic fungicides are highly effective, their repeated use has led to problems such as environmental pollution, development of resistance, and residual toxicity. This has prompted intensive research on the development of biopesticides, including botanical fungicides. To date, relatively few botanical fungicides have been registered and commercialized. However, many scientists have reported isolation and characterization of a variety of antifungal plant derivatives. Here, we present a survey of a wide range of reported plant-derived antifungal metabolites.

Activation of cholera toxin production by anaerobic respiration of trimethylamine N-oxide in Vibrio cholerae.

Vibrio cholerae is a gram-negative bacterium that causes cholera. Although the pathogenesis caused by this deadly pathogen takes place in the intestine, commonly thought to be anaerobic, anaerobiosis-induced virulence regulations are not fully elucidated. Anerobic growth of the V. cholerae strain, N16961, was promoted when trimethylamine N-oxide (TMAO) was used as an alternative electron acceptor. Strikingly, cholera toxin (CT) production was markedly induced during anaerobic TMAO respiration. N16961 mutants unable to metabolize TMAO were incapable of producing CT, suggesting a mechanistic link between anaerobic TMAO respiration and CT production. TMAO reductase is transported to the periplasm via the twin arginine transport (TAT) system. A similar defect in both anaerobic TMAO respiration and CT production was also observed in a N16961 TAT mutant. In contrast, the abilities to grow on TMAO and to produce CT were not affected in a mutant of the general secretion pathway. This suggests that V. cholerae may utilize the TAT system to secrete CT during TMAO respiration. During anaerobic growth with TMAO, N16961 cells exhibit green fluorescence when stained with 2',7'-dichlorofluorescein diacetate, a specific dye for reactive oxygen species (ROS). Furthermore, CT production was decreased in the presence of an ROS scavenger suggesting a positive role of ROS in regulating CT production. When TMAO was co-administered to infant mice infected with N16961, the mice exhibited more severe pathogenic symptoms. Together, our results reveal a novel anaerobic growth condition that stimulates V. cholerae to produce its major virulence factor.

Vitamin B12-mediated restoration of defective anaerobic growth leads to reduced biofilm formation in Pseudomonas aeruginosa.

Pseudomonas aeruginosa undergoes cell elongation and forms robust biofilms during anaerobic respiratory growth using nitrate (NO(3)(-)) as an alternative electron acceptor. Understanding the mechanism of cell shape change induced upon anaerobiosis is crucial to the development of effective treatments against P. aeruginosa biofilm infection. Here, we uncovered the molecular basis of anaerobiosis-triggered cell elongation and identified vitamin B(12) to be a molecule that can reinstate defective anaerobic growth of P. aeruginosa. The ratio of total cellular DNA content to protein content was significantly decreased in the PAO1 strain grown under anaerobic conditions, indicating that DNA replication is impaired during anaerobic growth. Anaerobic growth of PAO1 reached a higher cell density in the presence of vitamin B(12), an essential coenzyme of class II ribonucleotide reductase. In addition, cell morphology returned to a normal rod shape and transcription of stress-response genes was downregulated under the same anaerobic growth conditions. These results suggest that vitamin B(12), the production of which was suppressed during anaerobic growth, can restore cellular machineries for DNA replication and therefore facilitate better anaerobic growth of P. aeruginosa with normal cell division. Importantly, biofilm formation was substantially decreased when grown with vitamin B(12), further demonstrating that anaerobiosis-induced cell elongation is responsible for robust biofilm formation. Taken together, our data reveal mechanistic details of a morphological change that naturally occurs during anaerobic growth of P. aeruginosa and illustrates the ability of vitamin B(12) to modulate the biofilm-forming capacity of P. aeruginosa under such condition.

Potent in vivo antifungal activity against powdery mildews of pregnane glycosides from the roots of Cynanchum wilfordii.

Two new pregnane glycosides, kidjoranine 3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 4)-α-L-cymaropyranosyl-(1 → 4)-ß-D-cymaropyranosyl-(1→4)-α-L-diginopyranosyl-(1 → 4)-ß-D-cymaropyranoside (5) and caudatin 3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranosyl-(1 → 4)-α-L-cymaropyranosyl-(1 → 4)-ß-D-cymaropyranosyl-(1 → 4)-α-L-diginopyranosyl-(1 → 4)-ß-D-cymaropyranoside (6), were isolated from the roots of Cynanchum wilfordii along with four known compounds (1-4). The antifungal activities of the six compounds against barley powdery mildew caused by Blumeria graminis f. sp. hordei were compared to the antifungal activity of polyoxin B. The caudatin glycosides (1, 4, and 6) showed stronger antifungal activities than polyoxin B, whereas kidjoranine glycosides (2, 3, and 5) had weaker activities than polyoxin B. A wettable powder-type formulation (C. wilfordii-WP20) of the ethyl acetate extract from C. wilfordii roots prohibited the development of barley powdery mildew much more effectively than the commercial fungicide polyoxin B-WP10. In addition, C. wilfordii-WP20 effectively controlled strawberry powdery mildew caused by Sphaerotheca humuli under greenhouse conditions. Thus, the crude extract containing the pregnane glycosides can be used as a botanical fungicide for the environmentally benign control of powdery mildews.

A multicenter epidemiological study of acne vulgaris in Korea.

BACKGROUND: Acne is a common skin disorder that affects both adolescents and adults. However, few epidemiological studies on this condition have been conducted in Asia. OBJECTIVES: The purpose of this study was to analyze the incidence of acne and to identify its demographic and clinical features and aggravating factors. In addition, we examined the relationships between these factors. METHODS: Epidemiological and clinical data were obtained, using a self-administered questionnaire, from patients who visited 17 general hospitals and from the consulting dermatologists. RESULTS: A total of 1236 patients were involved in this study. Acne first developed and presented most commonly on the forehead and cheeks, although the cheeks were more severely affected. Significant associations were found between the clinical, epidemiological, and behavioral characteristics of acne patients according to several factors, such as sex, age at onset, previous treatment history, and family history. The present study indicates that stress, lack of sleep, smoking, alcohol consumption, and menstruation aggravate acne. CONCLUSIONS: This study presents the demographic features and clinical characteristics of acne sufferers in Korea. This large-scale analysis provides a useful overview of acne in Korea.

Anaerobiosis-induced loss of cytotoxicity is due to inactivation of quorum sensing in Pseudomonas aeruginosa.

Pseudomonas aeruginosa, an opportunistic pathogen of clinical importance, causes chronic airway infections in patients with cystic fibrosis (CF). Current literature suggests that pockets with reduced oxygen tension exist in the CF airway mucus. However, virulence features of this opportunistic pathogen under such conditions are largely unknown. Cell-free supernatant of the standard laboratory P. aeruginosa strain PAO1 obtained from anaerobic culture, but not aerobic culture, failed to kill A549 human airway epithelial cells. Further investigation revealed that this reduced cytotoxicity upon anaerobiosis was due to the suppressed secretion of elastase, a virulence factor controlled by P. aeruginosa quorum sensing (QS). Both a lacZ-reporter fusion assay and quantitative real-time PCR (RT-PCR) analysis demonstrated that transcription of the elastase-encoding lasB gene was substantially decreased during anaerobic growth compared with aerobic growth. Moreover, transcription of other genes controlled by the LasI/R QS system, such as rhlR, vqsR, mvfR, and rsaL, was also repressed under the same anaerobic growth conditions. Importantly, synthesis of 3-oxo-C(12)-HSL (PAI-1), an autoinducer molecule that mediates induction of the LasI/R QS system, was >22-fold decreased during anaerobic growth while C(4)-HSL (PAI-2), which mediates RhlI/R QS, was nondetectable under the same growth conditions. Transcription of the lasB gene was restored by exogenous supplementation with autoinducers, with PAI-2 more effective than PAI-1 or Pseudomonas quinolone signal (PQS) at restoring transcription of the lasB gene. Together, these results suggest that anaerobiosis deprives P. aeruginosa of the ability to regulate its virulence via QS and this misregulation attenuates the pathogenic potential of this important pathogen.

Inhibitory effects of broccoli extract on Escherichia coli O157:H7 quorum sensing and in vivo virulence.

Broccoli extract (BE) has numerous beneficial effects on human health including anticancer activity. Quorum sensing (QS), mediated by self-produced autoinducer (AI) molecules, is a key process for the production of virulence determinants in pathogenic bacteria. BE suppressed AI-2 synthesis and AI-2-mediated bacterial motility in a dose-dependent manner in Escherichia coli O157:H7. In addition, expression of the ler gene that regulates AI-3 QS system was also diminished in response to treatment with BE. Furthermore, in an in vivo efficacy test using Caenorhabditis elegans as a host organism, C. elegans fed on E. coli O157:H7 in the presence of BE survived longer than those fed solely on the pathogenic bacteria. Quantitative real-time PCR analysis indicated that quercetin was the most active among the tested broccoli-derived compounds in downregulating virulence gene expression, while treatment with myricetin significantly suppressed the expression of the eae gene involved in type III secretion system. These data suggest that BE and its flavonoid constituents can inhibit expression of QS-associated genes, thereby downregulating the virulence attributes of E. coli O157:H7 both in vitro and in vivo. This study clearly elucidates BE's QS-inhibitory activity and suggests that BE has the potential to be developed as an anti-infective agent.

Clinical and histological evaluation of 1% nadifloxacin cream in the treatment of acne vulgaris in Korean patients.

OBJECTIVES: Nadifloxacin is a fluoroquinolone with broad-spectrum antibacterial activity. Although it is used as an acne treatment in some European countries, it has not been used to treat Korean acne patients. We aimed to evaluate the clinical efficacy and safety of 1% nadifloxacin cream and the histological changes it incurs when used to treat mild to moderate facial acne in Korean patients. METHODS: An eight-week, randomized, prospective, split-face, double-blind, vehicle-controlled trial was performed. All participants were treated with 1% nadifloxacin cream on one-half of the face and vehicle cream on the other, twice per day for eight weeks. RESULTS: At final visits, inflammatory acne lesions were reduced by 70% on nadifloxacin-treated skin and increased by 13.5% on vehicle-treated skin; non-inflammatory acne lesions showed reductions of 48.1 and 10.1%, respectively. A significant difference was observed between the two treatments at four weeks. Histopathological examinations of the acne lesions showed decreased inflammation and interleukin-8 expression but no change in transforming growth factor-ß expression in nadifloxacin-treated skin compared with vehicle-treated skin after eight weeks of treatment. CONCLUSIONS: Nadifloxacin 1% cream is an effective, safe, and well-tolerated topical treatment for Korean patients with mild to moderate acne vulgaris. Histopathological changes after nadifloxacin treatment were well correlated with clinical outcomes. Therefore, nadifloxacin can be used as an effective and safe treatment option in the management of mild to moderate acne in Asian subjects.