Antibacterial activity of silver‐doped manganese dioxide nanoparticles on multidrug‐resistant bacteria

BACKGROUND: As a result of evolution of multiple drug resistance in human pathogens (bacteria) there is increasing demand for novel antibacterial agents, and recently, due to their high antibacterial and catalytic activities, metal nanoparticles have attracted the attention of researchers and medical microbiologists worldwide. RESULTS: Ni‐, Ce‐ and Ag‐doped MnO₂ nanoparticles were synthesized by a co‐precipitation method. Antibacterial activity of these synthesized nanoparticles on methicillin‐resistant Staphylococcus aureus and lead‐resistant Pseudomonas aeruginosa strain 4EA was investigated using a disc diffusion method. Only Ag‐doped MnO₂ nanoparticles showed an antibacterial property against methicillin‐resistant Staphylococcus aureus and lead‐resistant Pseudomonas aeruginosa strain 4EA at low levels of 60 µg/disc and 85 µg/disc, respectively. Scanning electron microscopy and transmission electron microscopy (SEM‐TEM) coupled with energy dispersive X‐ray (EDX) analysis revealed the nano‐size and composition of these synthesized nanoparticles. CONCLUSION: It was confirmed through a disc diffusion method that chemically synthesized silver doped MnO₂ nanoparticles have antibacterial activity against multidrug‐resistant Staphylococcus aureus and lead‐resistant Pseudomonas aeruginosa strain 4EA at low levels therefore these nanoparticles can be employed to fight and prevent infections caused by multidrug‐resistant bacterial pathogens. © 2012 Society of Chemical Industry     

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

A series of benzimidazole–quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2‐fluorobenzyl derivative 5 b (ethyl 7‐chloro‐6‐fluoro‐1‐[[1‐[(2‐fluorophenyl)methyl]benzimidazol‐2‐yl]methyl]‐4‐oxo‐quinoline‐3‐carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep‐2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV–DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b . Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug‐resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.     

Active Efflux Influences the Potency of Quorum Sensing Inhibitors in Pseudomonas aeruginosa

Many bacteria regulate gene expression through a cell–cell signaling process called quorum sensing (QS). In proteobacteria, QS is largely mediated by signaling molecules known as N‐acylated L ‐homoserine lactones (AHLs) and their associated intracellular LuxR‐type receptors. The design of non‐native small molecules capable of inhibiting LuxR‐type receptors (and thereby QS) in proteobacteria is an active area of research, and numerous lead compounds are AHL derivatives that mimic native AHL molecules. Much of this previous work has focused on the pathogen Pseudomonas aeruginosa, which controls an arsenal of virulence factors and biofilm formation through QS. The MexAB‐OprM efflux pump has been shown to play a role in the secretion of the major AHL signal in P. aeruginosa, N‐(3‐oxododecanoyl) L ‐homoserine lactone. In the current study, we show that a variety of non‐native AHLs and related derivatives capable of inhibiting LuxR‐type receptors in P. aeruginosa display significantly higher potency in a P. aeruginosa Δ(mexAB‐oprM) mutant, suggesting that MexAB‐OprM also recognizes these compounds as substrates. We also demonstrate that the potency of 5,6‐dimethyl‐2‐aminobenzimidazole, recently shown to be a QS and biofilm inhibitor in P. aeruginosa, is not affected by the presence/absence of the MexAB‐OprM pump. These results have implications for the use of non‐native AHLs and related derivatives as QS modulators in P. aeruginosa and other bacteria, and provide a potential design strategy for the development of new QS modulators that are resistant to active efflux.     

Chemical Synthesis and Biological Screening of 2‐Aminoimidazole‐Based Bacterial and Fungal Antibiofilm Agents

A collection of 2‐aminoimidazole/triazole amides has been synthesized and screened for antibiofilm activity. This class of small molecules was found to modulate the biofilm activity of Pseudomonas aeruginosa, a multidrug‐resistant strain of Acinetobacter baumannii (MDRAB), a methicillin‐resistant Staphylococcus aureus strain (MRSA), Escherichia coli, Rhodospirillum salexigens, Staphylococcus epidermidis, Vibrio vulnificus, and vancomycin‐resistant Enterococcus faecium as well as the yeast Candida albicans and Cryptococcus neoformans. Furthermore, lead compounds were found to not lyse red blood cells at active concentrations.     

The importance of the trans-enamine intermediate as a β-lactamase inhibition strategy probed in inhibitor-resistant SHV β-lactamase variants

The ability of bacteria to express inhibitor‐resistant (IR) β‐lactamases is stimulating the development of novel inhibitors of these enzymes. The 2′β‐glutaroxypenicillinate sulfone, SA2‐13, was previously designed to enhance the stabilization of the deacylation‐refractory, trans‐enamine inhibitory intermediate. To test whether this mode of inhibition can overcome different IR mutations, we determined the binding mode of SA2‐13 through X‐ray crystallography, obtaining co‐crystals of the inhibitor–protein complex by soaking crystals of the IR sulfhydryl variable (SHV) β‐lactamase variants S130G and M69V with the inhibitor. The 1.45 Å crystal structure of the S130G SHV:SA2‐13 complex reveals that SA2‐13 is still able to form the stable trans‐enamine intermediate similar to the wild‐type complex structure, yet with its carboxyl linker shifted deeper into the active site in the space vacated by the S130G mutation. In contrast, data from crystals of the M69V SHV:SA2‐13 complex at 1.3 Å did not reveal clear inhibitor density indicating that this IR variant disfavors the trans‐enamine conformation, likely due to a subtle shift in A237.     

A comparative study of the bactericidal effect of photocatalytic oxidation by TiO2 on antibiotic‐resistant and antibiotic‐sensitive bacteria

BACKGROUND: In recent decades, the increase in antibiotic‐resistant bacteria has become one of the most significant problems in public health. Titanium dioxide (TiO₂) has the potential to inactivate antibiotic‐resistant bacteria. RESULTS: In this study, TiO₂ that had been activated by ultraviolet A (UV‐A) irradiation was used to inactivate the following three antibiotic‐resistant bacteria in suspension: methicillin‐resistant Staphylococcus aureus (MRSA), multidrug‐resistant Acinetobacter baumannii (MDRAB) and vancomycin‐resistant Enterococcus faecalis (VRE). For comparison, the following antibiotic‐sensitive strains were used as controls: S. aureus (MSSA), A. baumannii (MDSAB), E. faecalis (VSE), Escherichia coli and the bacteriophage MS2. Results demonstrated that MSSA and MRSA were equally susceptible to TiO₂ photocatalysis, and the susceptibility of MDRAB was double that of MDSAB (P < 0.05). The susceptibility of VSE was 2.4 times that of VRE (P < 0.05). The results obtained from multiple regression analysis indicated that TiO₂ reaction time had the greatest influence on microbial survival following TiO₂ exposure in the presence of UV‐A. CONCLUSION: The development of antibiotic resistance does not appear to be correlated to increased resistance to TiO₂ photocatalysis, but TiO₂ in the presence of UV‐A still effectively reduces the number of antibiotic‐resistant microbes in suspension by 1–3 logs. Copyright © 2010 Society of Chemical Industry     

Scaffold‐Hopping of Multicationic Amphiphiles Yields Three New Classes of Antimicrobials

Quaternary ammonium compounds (QACs) are a vital class of antiseptics. Recent investigations into their construction are uncovering novel and potent multicationic variants. Based on a trisQAC precedent, we have implemented a scaffold‐hopping approach to develop alternative QAC architectures that display 1–3 long alkyl chains in specific projections from cyclic and branched core structures bearing 3–4 nitrogen atoms. The preparation of 30 QAC structures allowed for correlation of scaffold structure with antimicrobial activity. We identified QACs with limited conformational flexibility that have improved bioactivity against planktonic bacteria as compared to their linear counterparts. We also confirmed that resistance, as evidenced by an increased minimum inhibitory concentration (MIC) for methicillin‐resistant Staphylococcus aureus (MRSA) compared to methicillin‐susceptible Staphylococcus aureus (MSSA), can reduce efficacy up to 64‐fold for monocationic QACs. Differentiation of antimicrobial and anti‐biofilm activity, however, was not observed, suggesting that these compounds utilize a non‐specific mode of eradication.     

Synthesis and Antiplasmodial Activity of Novel Chloroquine Analogues with Bulky Basic Side Chains

Chloroquine is commonly used in the treatment and prevention of malaria, but Plasmodium falciparum, the main species responsible for malaria‐related deaths, has developed resistance against this drug. Twenty‐seven novel chloroquine (CQ) analogues characterized by a side chain terminated with a bulky basic head group, i.e., octahydro‐2H‐quinolizine and 1,2,3,4,5,6‐hexahydro‐1,5‐methano‐8H‐pyrido[1,2‐a][1,5]diazocin‐8‐one, were synthesized and tested for activity against D‐10 (CQ‐susceptible) and W‐2 (CQ‐resistant) strains of P. falciparum. Most compounds were found to be active against both strains with nanomolar or sub‐micromolar IC₅₀ values. Eleven compounds were found to be 2.7‐ to 13.4‐fold more potent than CQ against the W‐2 strain; among them, four cytisine derivatives appear to be of particular interest, as they combine high potency with low cytotoxicity against two human cell lines (HMEC‐1 and HepG2) along with easier synthetic accessibility. Replacement of the 4‐NH group with a sulfur bridge maintained antiplasmodial activity at a lower level, but produced an improvement in the resistance factor. These compounds warrant further investigation as potential drugs for use in the fight against malaria.     

Ceramide in Pseudomonas aeruginosa infections

Cystic fibrosis (CF), the most common autosomal recessive disorder, at least in western countries, is caused by mutations of the cystic fibrosis transmembranous conductance regulator (CFTR) molecule and affects approximately 80,000 patients in Europe and the USA. Most, if not all, CF patients develop a chronic pulmonary infection with Pseudomonas aeruginosa. At present it is unknown why CF patients are highly sensitive to P. aeruginosa infections, and most importantly, no curative treatment for CF is available. P. aeruginosa infection results in an activation of the enzyme acid sphingomyelinase which catalyzes the release of ceramide from sphingomyelin in the cell membrane. Ceramide forms large ceramide‐enriched membrane domains that are required for internalization of bacteria, induction of cell death in infected cells and a controlled release of cytokines from infected cells. Ceramide‐enriched membrane platforms seem to serve the reorganization of receptors and intracellular signaling molecules involved in the infection of mammalian cells with P. aeruginosa. The significance of the acid sphingomyelinase and ceramide for the infection of mammalian cells with P. aeruginosa was demonstrated on mice genetically deficient for the acid sphingomyelinase. Further studies with N. gonorrhoeae, S. aureus and rhinoviruses indicate that ceramide‐enriched membrane domains are also important for the infection of mammalian cells with other bacterial and viral pathogens, suggesting a general role of these membrane domains in infectious biology.     

Structure–Activity Relationships of 2‐Sufonylpyrimidines as Quorum‐Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa

Drug‐resistant Pseudomonas aeruginosa (PA) strains are on the rise, making treatment with current antibiotics ineffective. Hence, circumventing resistance or restoring the activity of antibiotics by novel approaches is of high demand. Targeting the Pseudomonas quinolone signal quorum sensing (PQS‐QS) system is an intriguing strategy to abolish PA pathogenicity without affecting the viability of the pathogen. Herein we report the structure–activity relationships of 2‐sulfonylpyrimidines, which were previously identified as dual‐target inhibitors of the PQS receptor PqsR and the PQS synthase PqsD. The SAR elucidation was guided by a combined approach using ligand efficiency and ligand lipophilicity efficiency to select the most promising compounds. In addition, the most effective inhibitors were rationally modified by the guidance of QSAR using Hansch analyses. Finally, these inhibitors showed the capacity to decrease biofilm mass and extracellular DNA, which are important determinants for antibiotic resistance.     

Ozone Inactivation of Pseudomonas aeruginosa,Escherichia coli,Shigella sonnei and Salmonella typhimurium in Water.

Based on the properties of ozone as a strong germicidal agent, inactivation kinetics of Pseudomonas aeruginosa, Escherichia coli, Shigella sonnei and Salmonella typhimurium towards ozone in water were studied. The values of 90% inactivation (t₉₀) obtained varied from 0.20 minutes (2.4 mg/L, Escherichia coli ATCC 25922) to 8.33 minutes (0.39 mg/L, Pseudomonas aeruginosa wild strain). First order inactivation kinetics with respect to both the concentrations of ozone and microorganisms were found, resulting an overall second order inactivation kinetics. The ATCC strains showed to be the most sensitive toward ozone among all. Meanwhile, the environmental isolation of Pseudomonas aeruginosa was the most resistant and Escherichia coli the most sensitive wild strain. The longest time required to achieve total inactivation was 35 minutes.     

Biological Evaluation of Potent Triclosan‐Derived Inhibitors of the Enoyl–Acyl Carrier Protein Reductase InhA in Drug‐Sensitive and Drug‐Resistant Strains of Mycobacterium tuberculosis

New triclosan (TRC) analogues were evaluated for their activity against the enoyl–acyl carrier protein reductase InhA in Mycobacterium tuberculosis (Mtb). TRC is a well‐known inhibitor of InhA, and specific modifications to its positions 5 and 4′ afforded 27 derivatives; of these compounds, seven derivatives showed improved potency over that of TRC. These analogues were active against both drug‐susceptible and drug‐resistant Mtb strains. The most active compound in this series, 4‐(n‐butyl)‐1,2,3‐triazolyl TRC derivative 3 , had an MIC value of 0.6 μg mL^?1 (1.5 μM ) against wild‐type Mtb. At a concentration equal to its MIC, this compound inhibited purified InhA by 98 %, and showed an IC₅₀ value of 90 nM . Compound 3 and the 5‐methylisoxazole‐modified TRC 14 were able to inhibit the biosynthesis of mycolic acids. Furthermore, mc²4914, an Mtb strain overexpressing inhA, was found to be less susceptible to compounds 3 and 14 , supporting the notion that InhA is the likely molecular target of the TRC derivatives presented herein.     

Metabolomics Comparison of Drug-Resistant and Drug-Susceptible Pseudomonas aeruginosa Strain (Intra- and Extracellular Analysis)

Pseudomonas aeruginosa is a common human pathogen belonging to the ESKAPE group. The multidrug resistance of bacteria is a considerable problem in treating patients and may lead to increased morbidity and mortality rate. The natural resistance in these organisms is caused by the production of specific enzymes and biofilm formation, while acquired resistance is multifactorial. Precise recognition of potential antibiotic resistance on different molecular levels is essential. Metabolomics tools may aid in the observation of the flux of low molecular weight compounds in biochemical pathways yielding additional information about drug-resistant bacteria. In this study, the metabolisms of two P. aeruginosa strains were compared—antibiotic susceptible vs. resistant. Analysis was performed on both intra- and extracellular metabolites. The ¹H NMR method was used together with multivariate and univariate data analysis, additionally analysis of the metabolic pathways with the FELLA package was performed. The results revealed the differences in P. aeruginosa metabolism of drug-resistant and drug-susceptible strains and provided direct molecular information about P. aeruginosa response for different types of antibiotics. The most significant differences were found in the turnover of amino acids. This study can be a valuable source of information to complement research on drug resistance in P. aeruginosa.     

Mass Spectrometry Based Metabolomics to Identify Potential Biomarkers for Resistance in Barley against Fusarium Head Blight (<Emphasis Type="Italic">Fusarium graminearum</Emphasis>)

Resistance in Triticeae to fusarium head blight (FHB) is quantitatively inherited. Metabolomics as a tool was used to better understand the mechanisms of resistance and to identify potential FHB resistance biomarker metabolites in barley. Five FHB-resistant two-row barley genotypes (CIho 4196, Zhedar-1, Zhedar-2, Fredrickson, and Harbin-2r) and one FHB-susceptible genotype (CH 9520–30) were each inoculated with either pathogen-suspension or mock-solution. Disease severity, quantified as the proportion of spikelets diseased, varied among genotypes, being the greatest in CH 9520–30. Spikelets were sampled, metabolites extracted with aqueous methanol, and analyzed using an LC-ESI-LTQ-Orbitrap system. A pair wise, resistant vs. susceptible, t-test identified 1774 significant treatment peaks. Canonical discriminant analysis of peak abundance allowed the genotypes to be sorted into three clusters: (i) CH9520-30, (ii) Harbin-2r, (iii) the remaining four genotypes. The t-test was further used to identify resistance-related (RR) and pathogenesis-related (PR) metabolites. The pathogen-produced virulence factor deoxynivalenol (DON), and its detoxification product, DON-3-O-glucoside (D3G) were designated as resistance indicator (RI) metabolites. Metabolites (RR, PR, or RI) occurring in at least two resistant genotypes, showing a two-fold or greater abundance in resistant vs. susceptible lines, and also known to have plant defense functions were selected as potential FHB resistance biomarker metabolites. These included phenylalanine, p-coumaric acid, jasmonate, linolenic acid, total DON produced (TDP), and the proportion of DON converted to D3G (PDC). Total DON was the lowest in CIho 4196, while PDC was the highest in Zhedar-2. The application of RR, PR, and RI metabolites as potential biomarkers to enhance resistance is discussed.     

Isolation and Identification of Phenanthrene Degrading Bacteria from the Soil around Oil Company of Andimeshk and Investigation of Their Growth Kinetics

Polycyclic aromatic hydrocarbons are particularly important due to large distribution in the environment, high toxicity and their carcinogen and mutagen properties. The purpose of this study was isolation and identification of phenanthrene degrading bacteria from the soil around Oil Company of Andimeshk (Iran) and investigation of their growth kinetics. Sampling from three stations was done at two seasons, spring and summer. Phenanthrene degrading bacteria were isolated from soil using enrichment method. Bacterial identification was performed by biochemical tests and 16S rRNA gene sequencing. Minimum inhibitory concentrations (MIC) were determined at various concentrations of phenanthrene. Bacterial biodegradation rate was determined using HPLC analysis. Finally, the growth kinetics of resistant bacteria was determined with culturing at concentrations of 0.5–0.8 g/l of phenanthrene. According to biochemical and molecular tests Pseudomonas aeruginosa strain SBL, Bacillus cereus strain Z4B-11, Staphylococcus epidermidis, and Micrococcus luteus were identified as phenanthrene degrading bacteria. The results showed that P. aeruginosa SBL and B. cereus Z4B-11 with the greatest amount of MIC are the most phenanthrene resistant bacteria, respectively. These two strains degraded 70% and 50% of phenanthrene after one week of incubation, respectively. The most growth in different concentrations of phenanthrene belonged to P. aeruginosa SBL and B. cereus Z4B-11 while the least growth belonged to S. epidermidis and M. luteus, respectively. It could be concluded that two new strains SBL and Z4B-11 which were isolated in the soil around Oil Company of Andimeshk have relatively high potential to be used for bioremediation of phenanthrene.     

Chaperone Activity of Bicyclic Nojirimycin Analogues for Gaucher Mutations in Comparison with N‐(n‐nonyl)Deoxynojirimycin

Gaucher disease (GD), the most prevalent lysosomal storage disorder, is caused by mutations of lysosomal β‐glucosidase (acid β‐Glu, β‐glucocerebrosidase); these mutations result in protein misfolding. Some inhibitors of this enzyme, such as the iminosugar glucomimetic N‐(n‐nonyl)‐1‐deoxynojirimycin (NN‐DNJ), are known to bind to the active site and stabilize the proper folding for the catalytic form, acting as “chemical chaperones” that facilitate transport and maturation of acid β‐Glu. Recently, bicyclic nojirimycin (NJ) analogues with structure of sp² iminosugars were found to behave as very selective, competitive inhibitors of the lysosomal β‐Glu. We have now evaluated the glycosidase inhibitory profile of a series of six compounds within this family, namely 5‐N,6‐O‐(N′‐octyliminomethylidene‐NJ (NOI‐NJ), the 6‐thio and 6‐amino‐6‐deoxy derivatives (6S‐NOI‐NJ and 6N‐NOI‐NJ) and the corresponding galactonojirimycin (GNJ) counterparts (NOI‐GNJ, 6S‐NOI‐GNJ and 6N‐NOI‐GNJ), against commercial as well as lysosomal glycosidases. The chaperone effects of four selected candidates (NOI‐NJ, 6S‐NOI‐NJ, 6N‐NOI‐NJ, and 6S‐NOI‐GNJ) were further evaluated in GD fibroblasts with various acid β‐Glu mutations. The compounds showed enzyme enhancement on human fibroblasts with N188S, G202R, F213I or N370S mutations. The chaperone effects of the sp² iminosugar were generally stronger than those observed for NN‐DNJ; this suggests that these compounds are promising candidates for clinical treatment of GD patients with a broad range of β‐Glu mutations, especially for neuronopathic forms of Gaucher disease.     

Rhamnolipids: Production in bacteria other than Pseudomonas aeruginosa

Rhamnolipids produced by Pseudomonas aeruginosa are the most studied biosurfactants due to their potential applications in a wide variety of industries and the high levels of their production. However, even though these biosurfactants are already produced at an industrial scale, the fact that P. aeruginosa is an opportunistic pathogen impose a restriction for its large scale production due to the intrinsic health hazard of the process. Other bacterial species that have been reported to be rhamnolipid producers are the pathogens Burkholderia mallei and B. pseudomallei, and recently the non‐pathogenic B. thailandensis. This short review presents information on rhamnolipid production by bacteria different from P. aeruginosa, as well as some approaches that have been taken to produce rhamnolipids using non‐pathogenic bacteria by genetic engineering of different bacteria. The low frequency of occurrence of rhamnolipid production among natural isolates that are not P. aeruginosa or Burkholderia, as well as the absence of orthologs of the genes involved in rhamnolipid synthesis (rhl genes) among the hundreds of sequenced bacterial genomes, suggest that the rare reported cases of these type of rhamnolipid‐producing bacteria have acquired this trait through horizontal gene transfer either from P. aeruginosa or from a member of Burkholderia.     

Targeting the Central Pocket of the Pseudomonas aeruginosa Lectin LecA

Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate-binding proteins are central to the initial and later persistent infection processes, i. e. bacterial adhesion and biofilm formation. The biofilm matrix is a major resistance determinant and protects the bacteria against external threats such as the host immune system or antibiotic treatment. Therefore, the development of drugs against the P. aeruginosa biofilm is of particular interest to restore efficacy of antimicrobials. Carbohydrate-based inhibitors for LecA and LecB were previously shown to efficiently reduce biofilm formations. Here, we report a new approach for inhibiting LecA with synthetic molecules bridging the established carbohydrate-binding site and a central cavity located between two LecA protomers of the lectin tetramer. Inspired by in silico design, we synthesized various galactosidic LecA inhibitors with aromatic moieties targeting this central pocket. These compounds reached low micromolar affinities, validated in different biophysical assays. Finally, X-ray diffraction analysis revealed the interactions of this compound class with LecA. This new mode of action paves the way to a novel route towards inhibition of P. aeruginosa biofilms.     

Atomic‐Resolution Structure of a Class C β‐Lactamase and Its Complex with Avibactam

β‐Lactamases (BLs) are important antibiotic‐resistance determinants that significantly compromise the efficacy of valuable β‐lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non‐β‐lactam BL inhibitor introduced into clinical practice. Ceftazidime–avibactam represents one of the few last‐resort antibiotics available for the treatment of infections caused by near‐pandrug‐resistant bacteria. TRU‐1 is a chromosomally encoded AmpC‐type BL of Aeromonas enteropelogenes, related to the FOX‐type BLs and constitutes a good model for class C BLs. TRU‐1 crystals provided ultrahigh‐resolution diffraction data for the native enzyme and for its complex with avibactam. A comparison of the native and avibactam‐bound structures revealed new details in the conformations of residues relevant for substrate and/or inhibitor binding. Furthermore, a comparison of the TRU‐1 and Pseudomonas aeruginosa AmpC avibactam‐bound structures revealed two inhibitor conformations that were likely to correspond to two different states occurring during inhibitor carbamylation/recyclization.     

Synthesis and study of antimicrobial activity of bioconjugates of silver nanoparticles and endogenous antibiotics

Bioconjugates of silver nanoparticles and antimicrobial peptides of the bactenecin family, which are endogenous antibiotics, have been synthesized. The biological activity of the prepared bioconjugates has been evaluated. It has been established that the conjugates of silver nanoparticles with the peptide G-Bac3.4 exhibit an antimicrobial activity, including the activity with respect to the strain Pseudomonas aeruginosa resistant to traditional antibiotics and the strain Staphylococcus aureus (MRSA ATCC 33591) resistant to methicillin. It has been demonstrated that the complexes of silver nanoparticles with antimicrobial peptides do not possess a pronounced membranolytic effect inherent in peptides. The results obtained have made it possible to draw the conclusion that the properties of the synthesized conjugates differ from those characteristic of constituting peptides and silver nanoparticles.