Investigating the synergistic antibacterial effects of chlorogenic and p-coumaric acids on Shigella dysenteriae.

Chlorogenic acid (CGA) is a well-known plant secondary metabolite exhibiting multiple physiological functions. The present study focused on screening for synergistic antibacterial combinations containing CGA. The combination of CGA and p-coumaric acid (pCA) exhibited remarkably enhanced antibacterial activity compared to that when administering the treatment only. Scanning electron microscopy revealed that a low-dose combination treatment could disrupt the Shigella dysenteriae cell membrane. A comprehensive analysis using nucleic acid and protein leakage assay, conductivity measurements, and biofilm formation inhibition experiments revealed that co-treatment increased the cell permeability and inhibited the biofilm formation substantially. Further, the polyacrylamide protein- and agarose gel-electrophoresis indicated that the proteins and DNA genome of Shigella dysenteriae severely degraded. Finally, the synergistic bactericidal effect was established for fresh-cut tomato preservation. This study demonstrates the remarkable potential of strategically selecting antibacterial agents with maximum synergistic effect and minimum dosage exhibiting excellent antibacterial activity in food preservation.

The effect of mesenchymal stem cell conditioned medium incorporated within chitosan nanostructure in clearance of common gastroenteritis bacteria in-vitro and in-vivo.

Gastroenteritis infection is a major public health concern worldwide, especially in developing countries due to the high annual mortality rate. The antimicrobial and antibiofilm activity of human mesenchymal stem cell-derived conditioned medium (hMSCsCM) encapsulated in chitosan nanoparticles (ChNPs) was studied in vitro and in vivo against common gastroenteritis bacteria. The synthesized ChNPs were characterized using Zeta potential, scanning electron microscopy (SEM), and dynamic light scattering (DLS) techniques. HMSC-derived conditioned medium incorporated into chitosan NPs (hMSCsCM-ChNPs) composite was fabricated by chitosan nanoparticles loaded with BM-MSCs (positive for CD73 and CD44 markers). The antimicrobial and antibiofilm activity of composite was investigated against four common gastroenteritis bacteria (Campylobacter jejuni ATCC29428, Salmonella enteritidis ATCC13076, Shigella dysenteriae PTCC1188, and E. coli ATCC25922) in-vitro and in-vivo. Majority of ChNPs (96%) had an average particle size of 329 nm with zeta potential 7.08 mV. The SEM images confirmed the synthesis of spherical shape for ChNPs and a near-spherical shape for hMSCsCM-ChNPs. Entrapment efficiency of hMSCsCM-ChNPs was 75%. Kinetic profiling revealed that the release rate of mesenchymal stem cells was reduced following the pH reduction. The antibacterial activity of hMSCsCM-ChNPs was significantly greater than that of hMSCsCM and ChNPs at dilutions of 1:2 to 1:8 (P < 0.05) against four common gastroenteritis bacteria. The number of bacteria present decreased more significantly in the group of mice treated with the hMSCsCM-ChNPs composite than in the groups treated with hMSCsCM and ChNPs. The antibacterial activity of hMSCsCM against common gastroenteritis bacteria in an in vivo assay decreased from > 106 CFU/ml to approximately (102 to 10) after 72 h. Both in vitro and in vivo assays demonstrated the antimicrobial and antibiofilm activities of ChNPs at a concentration of 0.1% and hMSCsCM at a concentration of 1000 µg/ml to be inferior to that of hMSCsCM-ChNPs (1000 µg/ml + 0.1%) composite. These results indicated the existence of a synergistic effect between ChNPs and hMSCsCM. The designed composite exhibited notable antibiofilm and antibacterial activities, demonstrating optimal release in simulated intestinal lumen conditions. The utilization of this composite is proposed as a novel treatment approach to combat gastroenteritis bacteria in the context of more challenging infections.

An integrated in-silico approach for drug target identification in human pathogen Shigella dysenteriae.

Shigella dysenteriae, is a Gram-negative bacterium that emerged as the second most significant cause of bacillary dysentery. Antibiotic treatment is vital in lowering Shigella infection rates, yet the growing global resistance to broad-spectrum antibiotics poses a significant challenge. The persistent multidrug resistance of S. dysenteriae complicates its management and control. Hence, there is an urgent requirement to discover novel therapeutic targets and potent medications to prevent and treat this disease. Therefore, the integration of bioinformatics methods such as subtractive and comparative analysis provides a pathway to compute the pan-genome of S. dysenteriae. In our study, we analysed a dataset comprising 27 whole genomes. The S. dysenteriae strain SD197 was used as the reference for determining the core genome. Initially, our focus was directed towards the identification of the proteome of the core genome. Moreover, several filters were applied to the core genome, including assessments for non-host homology, protein essentiality, and virulence, in order to prioritize potential drug targets. Among these targets were Integration host factor subunit alpha and Tyrosine recombinase XerC. Furthermore, four drug-like compounds showing potential inhibitory effects against both target proteins were identified. Subsequently, molecular docking analysis was conducted involving these targets and the compounds. This initial study provides the list of novel targets against S. dysenteriae. Conclusively, future in vitro investigations could validate our in-silico findings and uncover potential therapeutic drugs for combating bacillary dysentery infection.

Identification of vaccine and drug targets in Shigella dysenteriae sd197 using reverse vaccinology approach.

Shigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.

Evaluation of the Anti-Shigellosis Activity of Dietary Isothiocyanates in Galleria mellonella Larvae.

Cruciferous vegetables, widely present in daily diets, are a rich source of organosulfur compounds with proven health benefits, especially chemopreventive or antioxidative effects. Isothiocyanate derivatives (ITCs) exhibit a broad spectrum of biological and pharmacological activity and recently, their antibacterial properties have been of particular importance. Here, we have focused on the anti-shigellosis activity of sulforaphane (SFN) and phenethyl ITC (PEITC). The genus Shigella causes gastroenteritis in humans, which constitutes a threat to public health. Production of a potent Stx toxin by S. dysenteriae type 1 results not only in more severe symptoms but also in serious sequela, including the hemolytic uremic syndrome. Here, we present evidence that two aliphatic and aromatic ITCs derivatives, SFN and PEITC, have an effective antibacterial potency against S. dysenteriae, also negatively regulating the stx gene expression. The molecular mechanism of this effect involves induction of the global stress-induced stringent response. ITCs also inhibit bacterial virulence against the Vero and HeLa cells. We present evidence for the therapeutic effect of sulforaphane and phenethyl ITC against a S. dysenteriae infection in the Galleria mellonella larvae model. Thus, our results indicate that isothiocyanates can be effectively used to combat dangerous bacterial infections.

Activity of the lyases LysSSE1 and HolSSE1 against common pathogenic bacteria and their antimicrobial efficacy in biofilms.

Bacillary dysentery is a common foodborne disease with an exaggerated mortality rate because of Shigella infection. With the increasing severity of Shigella infection, lyase has been considered as the most promising alternative to antimicrobial agents, owing to the emergence of resistant bacteria and the difficulty in disrupting and eliminating bacterial biofilms. In this study, we cloned and characterised HolSSE1 and LysSSE1, holin, and lysozyme from the S. dysenteriae phage SSE1 with extended bacterial host range against common gram-negative and gram-positive bacteria. In addition, the efficacy of HolSSE1 and LysSSE1 in removing bacterial biofilms was observed on polystyrene surfaces. Moreover, synergistic bacteriostasis was observed when they were used together. Alignment and structural model analysis showed that both HolSSE1 and LysSSE1 are T4 phage proteins that have not yet been identified. Therefore, HolSSE1 and LysSSE1 can be promising biocontrol agents for the prevention and treatment of various pathogenic infections.

Antimicrobial and antioxidant activity of catechin-3-o-rhamnoside isolated from the stem bark of Lannea kerstingii Engl. and K. Krause (Anacardiaceae).

Various epidemiological researches have shown that consumption of vegetables and fruits are essential to maintain health and prevent diseases but the emergence of more and more drug resistance bacteria has led to high mortality. Thus the study of the antimicrobial and antioxidant activities of a flavonoid (Catechin-3-o-rhamnoside) isolated for the first time from Lannea kerstingii. Catechin-3-o-rhamnoside was isolated using dry vacuum liquid chromatography. It was characterized using 1H-NMR, 13C-NMR and 2D NMR spectra. The antimicrobial activity was determined using agar diffusion and broth dilution method. Antioxidant activity was determined through reaction of the compound with DPPH radical. The compound was active against, Methicillin Resistant Staphylococcus aureus, S. aureus, B. subtilis, E. coli, K. pneumoniae, S. typhi, S. dysentariae, C. albicans and C. tropicalis with zone of inhibition ranging from 22.0±0.1 to 35.0±0.2mm and inactive against vancomycin resistant enterococci, Proteus mirabilis and C. ulcerans. The MIC ranged from 6.25 to 12.5µg/ml while the MBC/MFC ranged from 12.5 to 50.0µg/ml. The compound showed a high radical scavenging activity with EC50 of 46.87µg/ml. These results show a potential lead drug for resistant bacteria and natural antioxidants.

Epidemic and molecular characterization of fluoroquinolone-resistant Shigella dysenteriae 1 isolates from calves with diarrhea.

BACKGROUND: The widespread distribution of antimicrobial-resistant Shigella has become a recurrent challenge in many parts of the developing world. Previous studies indicate that the host of Shigella has expanded from humans to animals. This study aimed to investigate the prevalence of fluoroquinolone resistance and associated molecular characterization of S. dysenteriae 1 isolated from calves. RESULTS: All 38 unduplicated S. dysenteriae 1 isolates were collected from calves in Gansu Province from October 2014 to December 2016. According to MLST and PFGE analysis, these isolates were separated into 4 and 28 genotypes, respectively. The most common STs identified were ST228 (34.21%, 13/38) and ST229 (39.47%, 15/38), which were first found in the present study. All isolates harbored virulence genes, and the incidence of the seven virulence genes were ipaH (100%), ipaBCD (92.11%), stx (73.68%), ial (57.89%), sen (28.95%), set1A and set1B (0%). According to the results of antimicrobial susceptibilities, 76.32% (29/38) were resistant to fluoroquinolone and showed multidrug resistance. In a study on the polymorphism of quinolone resistance-determining region (QRDR) of gyrA/B and parC/E genes, we identified two mutations in gyrA (Ser83 → Leu and Asp87 → Asn) and parC (Ser80 → Ile and Ser83 → Leu), respectively. Among them, 55.17% (16/29) of resistant strains had the gyrA point mutations (Ser83 → Leu) and parC point mutation (Ser83 → Leu). Moreover, 41.38% (12/29) of isolates had all five point mutations of gyrA and parC. In addition, the prevalence of the plasmid-mediated quinolone resistance (PMQR) determinant genes was also investigated. All 29 fluoroquinolone-resistant isolates were positive for the aac (6')-Ib-cr gene but negative for qepA, except for SD001. In addition, only 6 (20.69%, 6/29) isolates harbored the qnr gene, including two with qnrB (6.90%, 2/29) and four with qnrS (13.79%, 4/29). CONCLUSION: Given the increased common emergence of multidrug resistant isolates, uninterrupted surveillance will be necessary to understand the actual epidemic burden and control this infection.

An in-vitro study on a novel six-phage cocktail against multi-drug resistant-ESBL Shigella in aquatic environment.

Shigella spp. are water-borne pathogens responsible for mild to severe cases bacilli dysentery all around the world known as Shigellosis. The progressively increasing of antibiotic resistance among Shigella calls for developing and establishing novel alternative therapeutic methods. The present study aimed to evaluate a novel phage cocktail of lytic phages against extended spectrum beta lactamase isolates of Shigella species in an aquatic environment. The phage cocktail containing six novel Shigella specific phages showed a broad host spectrum. The cocktail was very stable in aquatic environment. The cocktail resulted in about 99% decrease in the bacterial counts in the contaminated water by several species and strains of Shigella such as Shigella sonnei, Shigella flexneri and Shigella dysenteriae. Achieving such a high efficiency in this in-vitro study demonstrates a high potential for in-vivo and in-situ application of this phage cocktail as a bio-controlling agent against Shigella spp. contamination and infections.

Two new phthalide derivatives from the endophytic fungus Penicillium vulpinum isolated from Sophora tonkinensis.

Two new phthalide derivatives, (-)-3-carboxypropyl-7-hydroxyphthalide (1) and (-)-3-carboxypropyl-7-hydroxyphthalide methyl ester (2), were isolated from the endophytic fungus Penicillium vulpinum isolated from the Chinese medicinal plant Sophora tonkinensis. Their structures were elucidated using spectroscopic methods, mainly on 1D and 2D NMR. Compound 1 exhibited medium antibacterial activities against Bacillus subtilis, Shigella dysenteriae and Enterobacter areogenes with MIC values of 12.5-25 µg/mL, and 2 showed a medium inhibition to E. areogenes with MIC value of 12.5 µg/mL.

Ag impregnated sub-micrometer crystalline jute cellulose particles: Catalytic and antibacterial properties.

This work discussed the preparation of Ag nanoparticles (AgNPs) and AgNPs impregnated sub-micrometer crystalline jute cellulose (SCJC) particles using a green synthetic bioreduction method. The ultimate nanocomposite particles were named as SCJC/Ag. The crystalline structure of AgNPs was maintained in SCJC/Ag nanocomposte particles. The catalytic efficiency of SCJC/Ag nanocomposite particles were evaluated for the degradation of congo red (CR) and methylene blue (MB) using NaBH4 as reducing agent. A complete degradation of 20 mL of each CR (0.1 mM) and MB (0.05 mM) dye solution was achieved within 14 min when 0.005 mg mL-1 of SCJC/Ag nanocomposite particles was employed. SCJC/Ag nanocomposite particles also exhibited moderate antibacterial activities against Staphylococcus aureus, Escherichia coli, Shigella dysenteriae and Shigella boydii and the results were comparable with those of the reference AgNPs. SCJC/Ag nanocomposite particles were the most effective against Escherichia coli (E. coli) with minimum inhibitory concentration of 0.014 mg mL-1.

Effects of Curcumin and Silymarin on the Shigella dysenteriae and Campylobacter jejuni In vitro.

OBJECTIVE: Antimicrobial properties of silymarin and curcumin have been assessed against several infectious agents. The aim of this study was to investigate the anti-apoptotic and antibacterial effects of both compounds on the expression of genes among Shigella dysenteriae ATCC 12022 and Campylobacter jejuni subsp. jejuni strain ATCC 33560 standard strains. METHODS: S. dysenteriae and C. jejuni standard strains were prepared from reference laboratory. Additionally, two clinical multidrug-resistant (MDR) isolates were adopted. Silymarin and curcumin stocks were purchased from Sigma Corporation (USA), and after preparation of dilutions (0.5-512 µg/ml), the minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) were determined. Furthermore, the effect of 100 µg/ml of each compound was also evaluated on the expression of two gyrB and 16S rRNA housekeeping genes by quantitative real-time PCR (qRT-PCR). RESULTS: Silymarin MIC and MBC were 512 µg/ml and > 512 µg/ml against S. dysenteriae and > 512µg/ml against C. jejuni standard strains, respectively. Moreover, curcumin MIC and MBC concentrations were 256 µg/ml and 512 µg/ml, respectively for ATCC strains. Silymarin down-expressed the expression of gyrB gene in S. dysenteriae and gyrB and 16srRNA gene in C. jejuni significantly (p < 0.05) compared with unexposed strains. In addition, curcumin could down-express the both gyrB and 16S rRNA genes in both strains significantly (p < 0.05). For two MDR clinical isolates, both MIC and MBC of compounds were > 512 µg/ml. Addition of 100 µg/ml curcumin and silymarin to ampicillin (10 µg/ml) lowered the MIC of MDR S. dysenteriae to 256 µg/ml and 512 µg/ml, respectively. However, no MIC change was observed with regard to C. jejuni. CONCLUSION: In this study, curcumin and silymarin could inhibit the growth of S. dysenteriae and C. jejuni and 100 µg/ml sub-MIC levels exhibited the suppression of housekeeping genes. Combating pathogenic bacteria by compounds alternative to antibiotics in the era of antibiotic resistance is a proper strategy, though more studies using combinations of them are needed.

Development of quinolone resistance and prevalence of different virulence genes among Shigella flexneri and Shigella dysenteriae in environmental water samples.

The purpose of this study was to find out the mechanism of quinolone resistance in Shigella sp. isolated from environmental water samples from various parts of Kolkata, India. Out of 196 Shigella sp. isolated from 2014 to 2017, we selected 32 Shigella isolates for antimicrobial susceptibility tests. The minimum inhibitory concentrations (MIC) for quinolones ranged from 30 to 50 µg ml-1 for ofloxacin, 5-20 µg ml-1 for ciprofloxacin and 20-30 µg ml-1 for norfloxacin. A few amino acid changes were found in quinolone resistance determining region (QRDR) of gyrA. Mutations in gyrA lead to a higher increment of MIC of quinolones. Among the plasmid-mediated (PMQR) quinolone resistance genes investigated, qnrB and aac(6')-lb-cr genes were found in all isolates. qnrA and qnrS were found in 25% and 62% of the isolates, respectively. ipaH gene was found in all of the isolates followed by the presence of other virulence genes ial, sen and stx1. Almost all the isolates having high MICs showed efflux pump activity in drug accumulation assay. All the mechanisms may or may not be present in a single strain. Several types of efflux pumps, presence of PMQR genes and mutations in drug target site of QRDR region may play the crucial role for resistance in our isolates.

Combinations of Alchornea cordifolia, Cassytha filiformis and Pterocarpus santalinoides in diarrhoegenic bacterial infections.

OBJECTIVES: This study examines the rationale, if any, behind combining the extracts from the fruits of Alchornea cordifolia and Pterocarpus santalinoides and aerial parts of Cassytha filiformis in the traditional treatment of diarrhoegenic bacterial infections. RESULTS: Four diarrhoegenic bacterial isolates: Salmonella typhi, Shigellae dysenteriae, Escherichia coli and Staphylococcus aureus were used and their antibiotic susceptibility screening showed that they were multi-antibiotic resistant. The extracts exhibited activity against all the test isolates with minimum inhibitory concentration values ranging from 3.125 to 12.5 mg/mL. From the checkerboard assay, the fractional inhibitory concentration indices showed that C. filiformis has antagonistic and indifference activities in combination with either P. santalinoides or A. cordifolia. This showed that the combination of extracts from the fruits of A. cordifolia and P. santalinoides and aerial parts of C. filiformis is counterproductive and invalidates any claim for positive results in the management of diarrhoegenic bacterial infections.

Synthesis, characterization and use of iron oxide nano particles for antibacterial activity.

In this decade, the use of nano particles (NPs) against bacterial growth is increasing day by day due to remarkable alternative properties compared to molecular antibiotics. Thus, the use of iron oxide nanoparticles (IONPs) has proven one of the most important transition metals oxide-based remedy in nanotechnological advances and biological applications due to enriched biocompatibility of iron. In this study synthesis of IONPs was carried out via co-precipitation method. The crystallographic morphology of the synthesized particles was studied via X-ray diffraction which revealed cubic structure of the particles, whereas, the spinal shaped morphology of the prepared NPs was confirmed from scanning electron microscopy. Likewise, the presence of the major elements in the sample was determined through energy dispersive X-ray analysis characterization. Bactericidal effect of the NPs was assessed at pre-defined concentrations (50 and 100 µg/ml) against Gram +ve bacteria Staphylococcus aureus, Gram -ve bacteria Shigella dysentry and Escherichia coli. Bacterial strains, which demonstrate the potential of NPs. The purpose of this study was assessing the structure of the synthesized NPs for protective effect against harmful bacterial activity.

Effectiveness of aqueous and hydroalcoholic extracts of Acanthospermum australe (Loefl) Kuntze against diarrhea-inducing bacteria / Eficácia de extratos aquosos e hidroalcoólicos de Acanthospermum australe (Loefl) Kuntze contra bactérias indutoras de diarreia

Abstract Leaves and roots of Acanthospermum australe (Asteraceae) have been used in Brazilian folk medicine for the treatment of various ailments including diarrhea, skin diseases, blennorrhagia, dyspepsia, parasitic worms and malaria. The aim of study was to characterize the chemical profiles of the aqueous and hydroalcoholic extracts of leaves and roots of A. australe, and to evaluate their antimicrobial activities against diarrhea-inducing bacteria (Enterococcus faecalis, Shigella dysenteriae and Yersinia enterocolitica), as well as their cytotoxic properties. Aqueous leaf extracts were obtained by infusion, while aqueous root extracts were obtained by decoction. The hydroalcoholic leaf and root extracts were prepared by maceration in 90% ethanol for 3 days. Antimicrobial activity was assessed using standard techniques and cytotoxicity was evaluated using Chinese hamster ovary cells CHO-K1. Chemical analysis revealed the presence of tannins, flavonoids, saponins and phenolic compounds in the extracts. Although root extracts were not effective against E. faecalis, leaf extracts at concentrations of 20 mg/mL exhibited bactericidal activities against this microorganism. The hydroalcoholic root extract was unique in presenting a bactericidal effect against S. dysenteriae. None of the extracts showed bacteriostatic or bactericidal activities against Y. enterocolitica. The results presented herein demonstrate that the Gram-positive E. faecalis and the Gram-negative S. dysenteriae were susceptible to A. australe extracts, although bacteriostatic/bactericidal activities were only observed at concentrations considered too high for clinical application. Our results support the ethnopharmacological use of A. australe in the treatment of gastrointestinal disorders, particularly diarrhea caused by infectious bacteria, although further studies are required to determine the anti-diarrhea effects and the toxicities of the extracts in vivo.

Resumo Folhas e raízes de Acanthospermum australe (Asteraceae) têm sido usadas na medicina popular brasileira para o tratamento de várias doenças, incluindo diarreia, doenças de pele, blenorragia, dispepsia, vermes parasitas e malária. O objetivo deste estudo foi caracterizar os perfis químicos dos extratos aquosos e hidroalcoólicos das raízes e folhas de A. australe, e avaliar as suas atividades antimicrobianas contra as bactérias indutoras de diarreia (Enterococcus faecalis, Shigella dysenteriae e Yersinia enterocolitica), bem como sua citotoxicidade. Os extratos aquosos de folhas foram obtidos por infusão, enquanto que os extratos aquosos de raízes foram obtidos por decocção. Os extratos hidroalcoólicos de folhas e raízes foram preparados por maceração em etanol a 90% durante 3 dias. A atividade antimicrobiana foi avaliada utilizando técnicas padrão e a citotoxicidade foi avaliada utilizando células de ovário de hamster chinês CHO-K1. A análise química revelou a presença de taninos, flavonóides, saponinas e compostos fenólicos nos extratos. Apesar de extratos de raiz não foram eficazes contra E. faecalis, extratos de folhas em concentrações de 20 mg/mL apresentaram atividades bactericidas contra este microrganismo. O extrato hidroalcoólico de raiz foi o único a apresentar um efeito bactericida contra S. dysenteriae. Nenhum dos extratos apresentaram atividades bacteriostáticas ou bactericidas contra Y. enterocolitica. Os resultados apresentados demonstram que a bactéria Gram-positiva E. faecalis e a Gram-negativa S. dysenteriae foram suscetíveis aos extratos de A. australe, embora as atividades bacteriostáticos/bactericidas tenham sido apenas observados em concentrações consideradas elevadas para aplicação clínica. Os nossos resultados apoiam a utilização de etnofarmacológica de A. australe no tratamento de perturbações gastrointestinais, especialmente diarreia causadas por bactérias infecciosas, embora sejam necessários mais estudos para determinar os efeitos anti-diarreia e as toxicidades dos extratos in vivo.

Antimicrobial resistance profiles of Shigella dysenteriae isolated from travellers returning to the UK, 2004-2017.

PURPOSE: Antimicrobial resistance (AMR) profiles of 754 strains of Shigella dysenteriae isolated between 2004 and 2017 from UK travellers reporting symptoms of gastrointestinal (GI) disease were reviewed to look for evidence of emerging AMR associated with travellers' diarrhoea. METHODOLOGY: A travel history was provided for 72.7 % (548/754) of cases, of which 90.9 % (498/548) reported travel outside the UK within 7 days of onset of symptoms, and 9.1 % (50/498) reported no travel in that time frame. During the course of this study, whole genome sequencing (WGS) was implemented for GI disease surveillance, and we compared phenotypic AMR profiles with those derived from WGS data (n=133).Results/Key findings. The phenotypic and genotypic AMR results correlated well, with 90.1 % (121/133) isolates having concordant results to 10 classes of antimicrobials. Resistance to the first-line drugs commonly used in the treatment of shigellosis was observed throughout the study (ampicillin, 54.1%; chloramphenicol, 33.7 %; sulphonamides, 76.0 %; trimethoprim, 80.0%). Between 2004 and 2017, resistance to all classes of antimicrobials (except the phenicols) increased. The proportion of isolates exhibiting reduced susceptibility to ciprofloxacin increased from 3.8 % in 2004 to 75.7 % in 2017, and this was significantly associated with cases reporting travel to Asia compared to Africa (P<0.001). Of the 201 sequenced isolates, 3.0 % (20/201) had either blaCTX-M-15 or blaCMY-4. CONCLUSIONS: Increasing MDR, along with resistance to the fluroquinolones and the third generation cephalosporins, in Shigella dysenteriae causing travellers' diarrhoea provides further evidence for the need to regulatethe use of antimicrobial agents and continuous monitoring of emerging AMR.

Serotype Distribution and Antimicrobial Resistance of Shigella Species in Bangui, Central African Republic, from 2002 to 2013.

Shigella is a major cause of severe diarrhea in children less than the age of 5 years in sub-Saharan Africa. The aim of this study was to describe the (sub-)serotype distribution and antimicrobial susceptibility of Shigella serogroups from Centrafrican patients with diarrhea between 2002 and 2013. We collected 443 Shigella isolates in total. The most common serogroups were Shigella flexneri (N = 243, 54.9%), followed by Shigella sonnei (N = 90, 20.3%) and Shigella dysenteriae (N = 72, 16.3%). The high diversity of (sub-)serotypes of S. flexneri and S. dysenteriae may impede the development of an efficient vaccine. Rates of resistance were high for ampicillin, chloramphenicol, tetracycline, and cotrimoxazole but low for many other antimicrobials, confirming recommendations for the use of third-generation cephalosporins (only one organism resistant) and fluoroquinolones (no resistance). However, the detection of one extended-spectrum beta-lactamase-producing Shigella organism highlights the need for continued monitoring of antimicrobial drug susceptibility.

Synthesis and antimicrobial activity of new amino derivatives of pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine.

Annulated thienopyrimidine derivatives attracted big interest of the scientific community due to their broad spectrum of biological activities among which are the inhibition of phosphodiesterase, antiproliferative and antimicrobial activities. As a continuation of our studies on the synthesis and biological activity of fused thieno[3,2-d]pyrimidine derivatives, the goal of this paper is the synthesis and study of the properties of compounds containing different heterocycles such as fused thieno[2,3-b]pyridine and tetrazolo[1,5-c]pyrimidine in the same molecule. Thus, starting from the ethyl 1-amino-5-isopropyl-8,8-dimethyl-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate 1, efficient methods for obtaining new 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidines 6 and thieno[2,3-e]tetrazolo[1,5-c]pyrimidine 8 are described. The spectroscopic results showed that compound 8 in the solid state is exclusively in the tetrazolo tautomeric form, while in solution an azide-tetrazole equilibrium is present 8A/T. The possible antimicrobial activity of newly synthesized compounds against some gram-positive and gram-negative bacilli strains has been evaluated. The biological tests evidenced that some of them showed promising antimicrobial activity. Two compounds showed similar activity to the one of the used reference drug. The study of structure-activity relationships revealed that the activity of a compound depends mostly on the nature of substituent R1R2. According to the predicted docking studies our compounds could be DnaG inhibitors.

Promotion of quality standard of Chinese herbal medicine by the integrated and efficacy-oriented quality marker of Effect-constituent Index.

BACKGROUND: Multiple constituents have been applied currently as markers to control the quality of Chinese herbal medicine (CHM). However, those constituents are isolated from each other, failed to present their contribution differences to the bioeffect of CHM. Besides, a CHM for different clinic uses is often controlled by the same quality marker (Q-marker), which cannot correlate its efficacies differentially. PURPOSE: The study aims to promote the quality standard of CHM by the integrated and efficacy-oriented Q-marker of Effect-constituent Index (ECI). METHODS: With Coptidis Rhizoma (C. Rhizoma) as a case study, the Q-marker of ECI based on the integration of bioeffect and active constituents was developed. According to the efficacies of C. Rhizoma, we investigated its antibacterial and antineoplastic effects by microcalorimetry and MTT assay, respectively. High performance liquid chromatography was performed to determine the active constituents of C. Rhizoma extract simultaneously. ECIS of inhibition on Shigella dysenteriae (S. dysenteriae) and ECIH of inhibition on HepG2 cells were established by multi-indicator synthetic evaluation method. The organoleptic evaluation scores of C. Rhizoma samples were given by Delphi method. RESULTS: The correlation analysis showed that ECIS and ECIH were significantly correlated with the inhibiting effects of C. Rhizoma extract on the growth of S. dysenteriae (P < 0.01) and proliferation of HepG2 cells (P < 0.01), respectively. Moreover, ECI showed a good ability to distinguish and predict the bioeffect-based quality grade, whereas the organoleptic evaluation and chemical analysis failed to achieve it. Plus, some samples with lower ECIS showed higher ECIH and vice versa. CONCLUSIONS: The Q-marker of ECI is useful to associate different pharmacologic effects of C. Rhizoma containing multiple active constituents, which is beneficial for the improvement of quality standard of the CHM in an integrated, convenient, and differentiated way.