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1.
Pansong Zhang Qiao Guo Zhihua Wei Qin Yang Zisheng Guo Lixin Shen Kangmin Duan Lin Chen 《Molecules (Basel, Switzerland)》2021,26(6)
Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections. 相似文献
2.
Resistance to conventional antibiotics has raised worldwide attention. Notably, Methicillin‐resistant Staphylococcus aureus (MRSA) has become one of the most life‐threatening health concerns. Although effective against bacterial infections, conventional antibiotics have also showed a series of side effects such as gut microbiota imbalance. An alternative is in urgent need in order to combat bacterial infections. Antivirulence represents a new approach to circumvent these shortcomings, which focuses on disarming the “weapons” for pathogenicity without much selective pressure on bacterial survival. In this review, we place emphasis on the chemical modulation of biosynthesis, assembly, function and the regulation of some major virulence factors in S. aureus, which we hope will help the development of antivirulence modulators. 相似文献
3.
Boris Pejin Ana Ciric Ivo Karaman Mladen Horvatovic Jasmina Glamoclija Milos Nikolic 《Natural product research》2016,30(16):1847-1850
The antibiofilm and possible antiquorum sensing effects against the strain Pseudomonas aeruginosa PAO1 of five crude extracts of the freshwater bryozoan Hyalinella punctata (Hancock, 1850) were evaluated in vitro for the first time. H. punctata ethyl acetate extract (HpEtAc) exhibited the highest antibiofilm activity reducing the biofilm formation of P. aeruginosa PAO1 in the range of 80.63–88.13%. While all tested extracts reduced the twitching motility of the aforementioned bacterial strain, HpEtAc showed to be the most effective. Finally, at a concentration of 0.5 MIC, the same extract mostly inhibited the production of pyocyanin by P. aeruginosa PAO1 (71.53%). In comparison both with the positive controls used (streptomycin and ampicillin, 67.13 and 69.77%, respectively), HpEtAc was found to inhibit pyocyanin in a higher extent. An extensive chemical characterisation of this particular extract may result in isolation and identification of novel lead compounds targeting P. aeruginosa, an opportunistic human pathogen. 相似文献
4.
Victor M. Balcão Sérgio V. P. Barreira Thiago M. Nunes Marco V. Chaud Matthieu Tubino Marta M. D. C. Vila 《Applied biochemistry and biotechnology》2014,172(3):1194-1214
Bacteriophage particles have been reported as potentially useful in the development of diagnosis tools for pathogenic bacteria as they specifically recognize and lyse bacterial isolates thus confirming the presence of viable cells. One of the most representative microorganisms associated with health care services is the bacterium Pseudomonas aeruginosa, which alone is responsible for nearly 15 % of all nosocomial infections. In this context, structural and functional stabilization of phage particles within biopolymeric hydrogels, aiming at producing cheap (chromogenic) bacterial biosensing devices, has been the goal of a previous research effort. For this, a detailed knowledge of the bacterial diffusion profile into the hydrogel core, where the phage particles lie, is of utmost importance. In the present research effort, the bacterial diffusion process into the biopolymeric hydrogel core was mathematically described and the theoretical simulations duly compared with experimental results, allowing determination of the effective diffusion coefficients of P. aeruginosa in the agar and calcium alginate hydrogels tested. 相似文献
5.
Dávid Szamosvári Dr. Thomas Böttcher 《Angewandte Chemie (International ed. in English)》2017,56(25):7271-7275
The pathogen Pseudomonas aeruginosa produces over 50 different quinolones, 16 of which belong to the class of 2-alkyl-4-quinolone N-oxides (AQNOs) with various chain lengths and degrees of saturation. We present the first synthesis of a previously proposed unsaturated compound that is confirmed to be present in culture extracts of P. aeruginosa, and its structure is shown to be trans-Δ1-2-(non-1-enyl)-4-quinolone N-oxide. This compound is the most active agent against S. aureus, including MRSA strains, by more than one order of magnitude whereas its cis isomer is inactive. At lower concentrations, the compound induces small-colony variants of S. aureus, reduces the virulence by inhibiting hemolysis, and inhibits nitrate reductase activity under anaerobic conditions. These studies suggest that this unsaturated AQNO is one of the major agents that are used by P. aeruginosa to modulate competing bacterial species. 相似文献
6.
Hashimoto MC Prates RA Kato IT Núñez SC Courrol LC Ribeiro MS 《Photochemistry and photobiology》2012,88(3):590-595
Pseudomonas aeruginosa is considered one of the most important pathogens that represent life‐threatening risk in nosocomial environments, mainly in patients with severe burns. Antimicrobial photodynamic therapy (aPDT) has been effective to kill bacteria. The purpose of this study was to develop a burn wound and bloodstream infection model and verify aPDT effects on it. In vitro, we tested two wavelengths (blue and red LEDs) on a clinical isolate of P. aeruginosa strain with resistance to multiple antibiotics using HB:La+3 as photosensitizer. Verapamil® associated to aPDT was also studied. In vivo, P. aeruginosa‐infected burned mice were submitted to aPDT. Bacterial counting was performed on local infection and bloodstream. Survival time of animals was also monitored. In this study, aPDT was effective to reduce P. aeruginosa in vitro. In addition, Verapamil® assay showed that HB:La+3 is not recognized by ATP‐binding cassete (ABC) efflux pump mechanism. In the in vivo study, aPDT was able to reduce bacterial load in burn wounds, delay bacteremia and keep the bacterial levels in blood 2–3 logs lower compared with an untreated group. Mice survival was increased on 24 h. Thus, this result suggests that aPDT may also be a novel prophylactic treatment in the care of burned patients. 相似文献
7.
Jiao Xia Zou Wisely Chua Dr. Zheng Ser Shi Mei Wang Grace Shu Hui Chiang Kavitha Sanmugam Boon Yeow Tan Dr. Radoslaw M. Sobota Prof. Dr. Hao Li 《Angewandte Chemie (International ed. in English)》2023,62(33):e202307553
Ceramidases (CDases) are important in controlling skin barrier integrity by regulating ceramide composition and affording downstream signal molecules. While the functions of epidermal CDases are known, roles of neutral CDases secreted by skin-residing microbes are undefined. Here, we developed a one-step fluorogenic substrate, S-B , for specific detection of bacterial CDase activity and inhibitor screening. We identified a non-hydrolyzable substrate mimic, C6 , as the best hit. Based on C6 , we designed a photoaffinity probe, JX-1 , which efficiently detects bacterial CDases. Using JX-1 , we identified endogenous low-abundance PaCDase in a P. aeruginosa monoculture and in a mixed skin bacteria culture. Harnessing both S-B and JX-1 , we found that CDase activity positively correlates with the relative abundance of P. aeruginosa and is negatively associated with wound area reduction in clinical diabetic foot ulcer patient samples. Overall, our study demonstrates that bacterial CDases are important regulators of skin ceramides and potentially play a role in wound healing. 相似文献
8.
Recent decades have revealed that many bacterial species are capable of communicating with each other, and this observation
has been largely responsible for a paradigm shift in microbiology. Whereas it was previously believed that bacteria lived
as individual cells, it is now acknowledged that bacteria preferentially live in communities in the form of primitive organisms
in which the behavior of individual cells is coordinated by cell–cell communication, known as quorum sensing (QS). Bacteria
use QS for regulation of the processes involved in their interaction with each other, their environment, and, particularly,
higher organisms We have focused on Pseudomonas aeruginosa, an opportunistic pathogen producing more than 30 QS-regulated virulence factors. P. aeruginosa causes several types of nosocomial infection, and lung infection in cystic fibrosis (CF) patients. We review the role of
QS in the protective mechanisms of P. aeruginosa and show how disruption of the QS can be used as an approach to control this cunning aggressor. 相似文献
9.
Application of Fragment‐Based Screening to the Design of Inhibitors of Escherichia coli DsbA 下载免费PDF全文
Dr. Luke A. Adams Dr. Pooja Sharma Dr. Biswaranjan Mohanty Olga V. Ilyichova Dr. Mark D. Mulcair Dr. Martin L. Williams Ellen C. Gleeson Dr. Makrina Totsika Dr. Bradley C. Doak Dr. Sofia Caria Dr. Kieran Rimmer Dr. James Horne Dr. Stephen R. Shouldice Mansha Vazirani Dr. Stephen J. Headey Brent R. Plumb Prof. Jennifer L. Martin Dr. Begoña Heras Dr. Jamie S. Simpson Dr. Martin J. Scanlon 《Angewandte Chemie (International ed. in English)》2015,54(7):2179-2184
The thiol‐disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram‐negative bacteria. DsbA substrates include proteins involved in bacterial virulence. In the absence of DsbA, many of these proteins do not fold correctly, which renders the bacteria avirulent. Thus DsbA is a critical mediator of virulence and inhibitors may act as antivirulence agents. Biophysical screening has been employed to identify fragments that bind to DsbA from Escherichia coli. Elaboration of one of these fragments produced compounds that inhibit DsbA activity in vitro. In cell‐based assays, the compounds inhibit bacterial motility, but have no effect on growth in liquid culture, which is consistent with selective inhibition of DsbA. Crystal structures of inhibitors bound to DsbA indicate that they bind adjacent to the active site. Together, the data suggest that DsbA may be amenable to the development of novel antibacterial compounds that act by inhibiting bacterial virulence. 相似文献
10.
Muropeptides in Pseudomonas aeruginosa and their Role as Elicitors of β‐Lactam‐Antibiotic Resistance 下载免费PDF全文
Dr. Mijoon Lee Supurna Dhar Dr. Stefania De Benedetti Dr. Dusan Hesek Dr. Bill Boggess Dr. Blas Blázquez Prof. Kalai Mathee Prof. Shahriar Mobashery 《Angewandte Chemie (International ed. in English)》2016,55(24):6882-6886
Muropeptides are a group of bacterial natural products generated from the cell wall in the course of its turnover. These compounds are cell‐wall recycling intermediates and are also involved in signaling within the bacterium. However, the identity of these signaling molecules remains elusive. The identification and characterization of 20 muropeptides from Pseudomonas aeruginosa is described. The least abundant of these metabolites is present at 100 and the most abundant at 55,000 molecules per bacterium. Analysis of these muropeptides under conditions of induction of resistance to a β‐lactam antibiotic identified two signaling muropeptides (N‐acetylglucosamine‐1,6‐anhydro‐N‐acetylmuramyl pentapeptide and 1,6‐anhydro‐N‐acetylmuramyl pentapeptide). Authentic synthetic samples of these metabolites were shown to activate expression of β‐lactamase in the absence of any β‐lactam antibiotic, thus indicating that they serve as chemical signals in this complex biochemical pathway. 相似文献
11.
A novel series of 3,6-disubstituted coumarin derivatives were synthesized by the reaction of ethyl-2-(3-acetyl-2-oxo-2H-chromen-6-yl)-4-methylthiazole-5-carboxylate with thiosemicarbazide and various phenacyl bromides / 3-(2-bromoacetyl)-2H-chromen-2-ones / 2-(2-bromoacetyl)-3H-benzo[f]chromen-3-one in ethanol having catalytic amount of acetic acid under reflux conditions with good yields. All the synthesized compounds were fully characterized by spectral studies and evaluated for their in vitro antibacterial activity against Pseudomonas aeruginosa, Bacillus subtilis (Gram positive), Escherichia coli, and Azatobacter (Gram negative) bacterial strains. Activity results revealed that the compound 6h against Escherichia coli and compound 6i against Pseudomonas aeruginosa and Escherichia coli have shown maximum zones of inhibition. Remaining compounds showed moderate to good activity against all the tested bacterial strains compared with the standard drug cefotaxime. 相似文献
12.
Surfaces with antibacterial and hydrophilic properties are very attractive to cardiovascular applications. The objective of this study was to synthesize and immobilize a novel antibacterial and hydrophilic polymer onto surface of polyvinylchloride via an effective and mild surface coating technique. The surface coated with a terpolymer constructed with N‐vinylpyrrolidone, 3,4‐dichloro‐5‐hydroxy‐2(5H)‐furanone derivative, and succinimide residue was evaluated with cell adhesion, bacterial adhesion, and bacterial viability. 3T3 mouse fibroblast cells and two bacteria species were used to evaluate surface adhesion and antibacterial activity. Results showed that the polymer‐modified polyvinylchloride surface exhibited not only significantly decreased 3T3 fibroblast cell adhesion with a 66% to 87% reduction but also significantly decreased bacterial adhesion with 69% to 87% and 52% to 74% reduction of Pseudomonas aeruginosa and Staphylococcus aureus attachment, respectively, as compared with original polyvinylchloride. Furthermore, the modified polyvinylchloride surfaces exhibited significant antibacterial functions by inhibiting bacterial growth (75%‐84% and 78–94% inhibition of P aeruginosa and S aureus, respectively, as compared to original polyvinylchloride) and killing bacteria. These results demonstrate that covalent polymer attachment conferred antifouling and antibacterial properties to the polyvinylchloride surface. 相似文献
13.
Combining Topology and Sequence Design for the Discovery of Potent Antimicrobial Peptide Dendrimers against Multidrug‐Resistant Pseudomonas aeruginosa 下载免费PDF全文
Michaela Stach Thissa N. Siriwardena Dr. Thilo Köhler Prof. Dr. Christian van Delden Priv.‐Doz. Dr. Tamis Darbre Prof. Dr. Jean‐Louis Reymond 《Angewandte Chemie (International ed. in English)》2014,53(47):12827-12831
Multidrug‐resistant opportunistic bacteria, such as Pseudomonas aeruginosa, represent a major public health threat. Antimicrobial peptides (AMPs) and related peptidomimetic systems offer an attractive opportunity to control these pathogens. AMP dendrimers (AMPDs) with high activity against multidrug‐resistant clinical isolates of P. aeruginosa and Acinetobacter baumannii were now identified by a systematic survey of the peptide sequences within the branches of a distinct type of third‐generation peptide dendrimers. Combined topology and peptide sequence design as illustrated here represents a new and general strategy to discover new antimicrobial agents to fight multidrug‐resistant bacterial pathogens. 相似文献
14.
Since considerable intrigue has been focused on azetidinone (β-lactam) compounds for their wide range antimicrobial activity, the present study focuses on the synthesis of new series of azetidinone compounds. The reaction between the novel azomethine and α-haloester in the presence of Zn impetus and benzene resulted into the formation of desired azetidinone derivative by [2+2] cycloaddition involving imine–ketene. The reaction has also been studied in the presence of diverse Lewis acids such as Zn(OTf)2, ZnCl2, Cu(OTf)2, TiCl4, and BF3.Et2O. The effect of such Lewis acids also enhance the yield of the desired product. Moreover, the structure of the isolated products was also affirmed by spectral analysis (Fourier-transform infrared [FT-IR] spectroscopy, proton nuclear magnetic resonance [1H NMR], carbon-13 nuclear magnetic resonance [13C NMR], and high-resolution mass spectrometry [HRMS]). Furthermore, the antibacterial activity of synthesized compounds has been screened in vitro against different pathogenic bacterial and fungus species. Inspection of the results uncovered that all of the newly synthesized compounds individually display varying degrees of inhibitory impacts on the development of the tested bacterial species, thus, they might be considered as medication possibility for bacterial pathogens. The azomethine exhibited an expansive range of antibacterial activity against Gram-negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumannii and Gram-positive Staphylococcus aureus bacterial strains and antifungal activity against Candida albicans, Candida tropicalis, and Candida parapsilosis bacterial strain. The result demonstrated that the β-lactam subordinates have good antibacterial and antifungal activities on microscopic organisms. 相似文献
15.
Capillary electrophoresis approaches have been utilized for the study of bacteria under specific experimental conditions.
The main objective within our research work was to study electrophoretic behaviors of Pseudomonas aeruginosa by means of capillary electrophoresis with UV and fluorescence detection. Edwardsiella tarda and Enteropathogenic escherichia coli were also included in the study. The results showed that proper pretreatment (vortexing or sonication) for each bacterial
sample before injection was necessary to disperse the clusters of cells, which is helpful to observe the single peaks and
better peak shape of bacteria during electrophoresis. Apart from this, it was found that ionic strength of buffer affected
mobilities of Pseudomonas aeruginosa as a result of increasing of buffer concentration from 25 mM to 150 mM. Moreover, sharp and single peaks were still observed
without significant increase of noise in the concentration range. Eventually, mixtures of bacteria were well separated under
optimized separation conditions with UV and fluorescence detection. In the mean time, comparison of concentration sensitivities
for Pseudomonas aeruginosa by UV and fluorescence detection was made. Blue light emitting diode induced fluorescence detection was found to be more
sensitive (8.5-fold higher) than UV detection with home-made fluorescence detection system. Generally, proposed CE methods for the analysis of bacteria could be potentially valuable for the monitoring of bacteria contamination in real life. 相似文献
16.
Victor Markus Karina Golberg Kerem Teral Nazmi Ozer Esti Kramarsky-Winter Robert S. Marks Ariel Kushmaro 《Molecules (Basel, Switzerland)》2021,26(6)
Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date. 相似文献
17.
Dr. Giuliana Niro Stefanie C. Weck Prof. Dr. Christian Ducho 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(70):16875-16887
To overcome bacterial resistances, the need for novel antimicrobial agents is urgent. The class of so-called nucleoside antibiotics furnishes promising candidates for the development of new antibiotics, as these compounds block a clinically unexploited bacterial target: the integral membrane protein MraY, a key enzyme in cell wall (peptidoglycan) biosynthesis. Nucleoside antibiotics exhibit remarkable structural diversity besides their uridine-derived core motifs. Some sub-classes also show specific selectivities towards different Gram-positive and Gram-negative bacteria, which are poorly understood so far. Herein, the synthesis of a novel hybrid structure is reported, derived from the 5′-defunctionalized uridine core moiety of muraymycins and the peptide chain of sansanmycin B, as a new scaffold for the development of antimicrobial agents. The reported muraymycin–sansanmycin hybrid scaffold showed nanomolar activity against the bacterial target enzyme MraY, but displayed no significant antibacterial activity against S. aureus, E. coli, and P. aeruginosa. 相似文献
18.
Tsukasa Ikeda Yuki Inoue Akihito Suehiro Hirofumi Ikeshoji Takenori Ishida Noboru Takiguchi Akio Kuroda Junichi Kato Hisao Ohtake 《Journal of inclusion phenomena and macrocyclic chemistry》2002,44(1-4):381-382
Inclusion complex formation between cyclodextrin and autoinducer of gram negative bacteria in aqueous solution was investigated by 1D 1H-NMR and ROESY spectra. An inhibitioneffect was observed on autoinducer activities of quorum sensing in Pseudomonas aeruginosa by adding cyclodextrins to the bacterial culture medium. 相似文献
19.
Dr. Palanisamy Ravichandiran Prof. Maciej Masłyk Dr. Sunirmal Sheet Dr. Monika Janeczko Dr. Dhanraj Premnath Prof. Ae Rhan Kim Prof. Byung-Hyun Park Prof. Myung-Kwan Han Prof. Dong Jin Yoo 《ChemistryOpen》2019,8(5):589-600
1,4-Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4-naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram-positive and five Gram-negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus (S. aureus; 30–70 μg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Salmonella bongori (S. bongori; 70–150 μg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time-kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds. 相似文献
20.
Shaked Uzi-Gavrilov Zohar Tik Omer Sabti Prof. Michael M. Meijler 《Angewandte Chemie (International ed. in English)》2023,62(29):e202300585
Chemical communication between competing bacteria in multi-species environments often enables both species to adapt and survive, and perhaps even thrive. P. aeruginosa and S. aureus are two bacterial pathogens found in natural biofilms, especially in the lungs of cystic fibrosis (CF) patients, where recent studies showed that there is often cooperation between the two species, leading to increased disease severity and antibiotic resistance. However, the mechanisms behind this cooperation are poorly understood. In this study, we analyzed co-cultured biofilms in various settings, and we applied untargeted mass spectrometry-based metabolomics analyses, combined with synthetic validation of candidate compounds. We unexpectedly discovered that S. aureus can convert pyochelin into pyochelin methyl ester, an analogue of pyochelin with reduced affinity for iron (III). This conversion allows S. aureus to coexist more readily with P. aeruginosa and unveils a mechanism underlying the formation of robust dual-species biofilms. 相似文献