scholarly journals Variation in genome content and predatory phenotypes betweenBdellovibriosp. NC01 isolated from soil andB. bacteriovorustype strain HD100

2019 ◽  
Author(s):  
Laura E. Williams ◽  
Nicole Cullen ◽  
Joseph A. DeGiorgis ◽  
Karla J. Martinez ◽  
Justina Mellone ◽  
...  
Keyword(s):  
Horizontal Gene Transfer ◽  
Type Strain ◽  
Bacterial Infections ◽  
Clinical Applications ◽  
Gram Negative Bacteria ◽  
Ecological Significance ◽  
Gram Negative ◽  
E Coli ◽  
Predatory Bacteria ◽  
Genome Content

AbstractThe range of naturally occurring variation in the ability ofBdellovibriostrains to attack and kill Gram-negative bacteria is not well understood. Defining phenotypic and associated genotypic variation amongBdellovibriowill clarify how divergent lineages within this genus impact microbial communities and will inform development of predatory bacteria as biocontrol agents to combat bacterial infections. We isolatedBdellovibriosp. NC01 from soil and compared its genome and predatory phenotypes toB. bacteriovorustype strain HD100. Based on analysis of 16S rRNA gene sequences and average amino acid identity, NC01 belongs to a different species than HD100. Genome-wide comparisons and individual gene analyses indicated that eight NC01 genome regions were likely acquired by horizontal gene transfer (HGT), further supporting an important role for HGT inBdellovibriogenome evolution. Within these regions, multiple protein-coding sequences were assigned predicted functions related to transcriptional regulation and transport; however, most were annotated as hypothetical proteins. Compared to HD100, NC01 has a limited prey range and killsE. coliML35 less efficiently. Whereas HD100 drastically reduces the ML35 population and then maintains low prey population density, NC01 causes a smaller reduction in ML35, after which the prey population recovers, accompanied by a decrease in NC01. In addition, NC01 forms turbid plaques on lawns of ML35, in contrast to clear plaques formed by HD100. Characterizing variation in interactions betweenBdellovibrioand Gram-negative bacteria, such as observed with NC01 and HD100, is important for understanding the ecological significance of predatory bacteria and evaluating their effectiveness in clinical applications.ImportanceBdellovibrioattack and kill Gram-negative bacteria; however, not allBdellovibriostrains are equally efficient at killing the same Gram-negative bacteria. Defining howBdellovibriovary in predatory phenotypes and how this phenotypic variation relates to differences in genotype is important for understanding the ecological significance of predatory bacteria and evaluating their effectiveness in biocontrol of bacterial infections. We determined variation in genome content and predatory phenotypes, including prey range and predation efficiency, betweenBdellovibriosp. NC01 isolated from soil andB. bacteriovorustype strain HD100. NC01 is phylogenetically divergent from HD100, with eight regions of unique gene content likely acquired by horizontal gene transfer. Compared to HD100, the prey range of NC01 is limited, and it was less efficient at killing a strain ofE. coli. These differences may have important implications for how each strain impacts microbial communities in different environments and for the effectiveness of each in clinical applications.

scholarly journals Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R againstEscherichia coli

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3168 ◽  
Author(s):  
Diana Machado ◽  
Laura Fernandes ◽  
Sofia S. Costa ◽  
Rolando Cannalire ◽  
Giuseppe Manfroni ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Bacterial Infections ◽  
Efflux Pump ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Gram Negative ◽  
E Coli ◽  
Efflux Pump Inhibitors

Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone – PQQ4R), againstEscherichia coli,by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ). The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux inE. colireducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentrations. The time-kill studies showed that PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity associated with a fast decrease of the intracellular ATP levels. The results also indicated that the mode of action of PQQ4R involves the destabilization of theE. coliinner membrane potential and ATP production impairment, ultimately leading to efflux pump inhibition by interference with the energy required by the efflux systems. At bactericidal concentrations, membrane permeabilization increases and finally ATP is totally depleted leading to cell death. Since drug resistance mediated by the activity of efflux pumps depends largely on the proton motive force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future adjuvants of conventional therapy againstE. coliand other Gram-negative bacteria, especially their multidrug resistant forms. Their major limitation is the high toxicity for human cells at the concentrations needed to be effective against bacteria. Their future molecular optimization to improve the efflux inhibitory properties and reduce relative toxicity will optimize their potential for clinical usage against multi-drug resistant bacterial infections due to efflux.

scholarly journals Phylogenomics, Epigenomics, Virulome, and Mobilome of Gram-negative Bacteria Co-resistant to Carbapenems and Polymyxins: A One-Health Systematic Review and Meta-analyses

2021 ◽  
Author(s):  
Winnie Thabisa Ramaloko ◽  
John Osei Sekyere
Keyword(s):  
Bacterial Infections ◽  
One Health ◽  
Phylogenetic Analyses ◽  
Restriction Enzymes ◽  
Type I ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Meta Analyses ◽  
Restriction Modification

Gram-negative bacteria (GNB) continue to develop resistance against important antibiotics including last-resort ones such as carbapenems and polymyxins. An analysis of GNB with co-resistance to carbapenems and polymyxins from a One Health perspective is presented. Data of species name, country, source of isolation, resistance genes (ARGs), plasmid type, clones, and mobile genetic elements (MGEs) were deduced from 129 articles from January 2016 to March 2021. Available genomes and plasmids were obtained from PATRIC and NCBI. Resistomes and methylomes were analysed using BAcWGSTdb and REBASE whilst Kaptive was used to predict capsule typing. Plasmids and other MEGs were identified using MGE Finder and ResFinder. Phylogenetic analyses were done using RAxML and annotated with MEGA 7. A total of 877 isolates, 32 genomes and 44 plasmid sequences were analysed. Most of these isolates were reported in Asian countries and were isolated from clinical, animal, and environmental sources. Colistin resistance was mostly mediated by mgrB inactivation, while OXA-48/181 was the most reported carbapenemase. IncX and IncI were the most common plasmids hosting carbapenemases and mcr genes. The isolates were co-resistant to other antibiotics, with floR (chloramphenicol) and fosA3 (fosfomycin) being common; E. coli ST156 and K. pneumoniae ST258 strains were common globally. Virulence genes and capsular KL-types were also detected. Type I, II, III and IV restriction modification systems were detected, comprising various MTases and restriction enzymes. The escalation of highly resistant isolates drains the economy due to untreatable bacterial infections, which leads to increasing global mortality rates and healthcare costs.

Bacterial Pattern of Community acquired Urinary Tract Infections: A Challenge for Antimicrobial Resistance

2021 ◽  
Vol 30 (3) ◽  
pp. 153-162
Author(s):  
Nader A. Nemr ◽  
Rania M. Kishk ◽  
Mohammed Abdou ◽  
Hassnaa Nassar ◽  
Noha M Abu bakr Elsaid ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Diffusion Method ◽  
Gram Negative Bacteria ◽  
Isolation And Identification ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Tract Infections

Background: Urinary tract infection (UTI) is considered one of the most common bacterial infections seen in health care. To our knowledge, there is no available antimicrobial resistance surveillance system for monitoring of community-acquired UTIs (CA- UTIs) in our country. Objectives: we aimed to discuss the bacterial pattern and resistance profile of CA-UTIs in Ismailia, Egypt. Methods: This cross-sectional study included 400 patients suffering from symptoms of acute UTIs. Urine specimens were collected by clean-catch mid-stream method, examined microscopically and inoculated immediately on blood agar and MacConkey's agar plates. Colony counting, isolation and identification of the urinary pathogens were performed by the conventional biochemical tests according to the isolated organism. Antibiotic susceptibility testing was performed by Kirby Bauer disk diffusion method. Interpretation was performed according to Clinical Laboratory Standard Institute (CLSI) guidelines. Results: out of 400 specimens, 136 of them revealed no bacterial growth or insignificant bacteriuria. Most of participants with UTI were females (81.8%) (p=0.008) and 54.5% of them were married (P=0.1). Gram negative bacteria were more common than Gram positive representing 66 % and 34% respectively. E. coli was the most common isolated organism (39%) followed by S. aureus (32%), K. Pneumoniae and Pseudomonas (10.5% for each), Proteus (6%) and Enterococci (2%). E. coli isolates showed the highest susceptibility to imipenem, meropenem, amikacin, nitrofurantoin, levofloxacin and ciprofloxacin. Most of our patients were diabetics (64.8%) (p=0.004). The mean ± SD of HbA1c was 6.4±2.0 with 4 to 12.6 range, S.E was 0.1 and 95% C.I was 6.2- 6.7. The highest mean ± SD of HbA1c was in S. aureus infections. Conclusion: Gram negative bacteria were most common than Gram positive with predominance of E. coli with significant relation to the presence of diabetes.

Ability of Bdellovibrio bacteriovorus 109J to Lyse Gram-Negative Food-Borne Pathogenic and Spoilage Bacteria

1995 ◽  
Vol 58 (2) ◽  
pp. 160-164 ◽  
Author(s):  
PINA M. FRATAMICO ◽  
RICHARD C. WHITING
Keyword(s):  
Coli Strain ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Bdellovibrio Bacteriovorus ◽  
Gram Negative ◽  
E Coli ◽  
Food Borne Pathogens ◽  
Food Borne ◽  
Spoilage Bacteria ◽  
Predatory Bacteria

Bdellovibrios are a group of aerobic, predatory bacteria which attack, penetrate and grow in many species of gram-negative bacteria, causing the lysis of the invaded prey organism. Bdellovibrio bacteriovorus strain 109J varied in its ability to lyse 32 bacterial strains comprising six genera of food-borne pathogens and spoilage organisms. The reduction in the levels of the prey bacteria ranged from 0.1 to 7.7 log-values after 7 h of incubation at 30°C. Escherichia coli strain 2239-69 (pathogenic serotype 026:H11) was lysed most effectively at temperatures between 30 and 37°C, however, lysis also occurred at 12 and 19°C when the incubation period was extended to 24 h. Bdellovibrio bacteriovorus was effective in reducing the level of E. coli 2239-69 at pH 5.6 to 8.6. Increasing the Bdellovibrio: E. coli ratio resulted in a more rapid E. coli reduction. This study demonstrated the potential usefulness of bdellovibrios for the biological control of pathogenic and spoilage organisms in foods.

scholarly journals Prey range and genome evolution ofHalobacteriovorax marinuspredatory bacteria from an estuary

2017 ◽  
Author(s):  
Brett G. Enos ◽  
Molly K. Anthony ◽  
Joseph A. DeGiorgis ◽  
Laura E. Williams
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Codon Usage ◽  
Genome Evolution ◽  
Genome Analysis ◽  
Regulation Of Gene Expression ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Predatory Bacteria ◽  
The Impact

AbstractBackgroundHalobacteriovoraxare saltwater-adapted predatory bacteria that attack Gram-negative bacteria and therefore may play an important role in shaping microbial communities. To understand the impact ofHalobacteriovoraxon ecosystems and develop them as biocontrol agents, it is important to characterize variation in predation phenotypes such as prey range and investigate the forces impactingHalobacteriovoraxgenome evolution across different phylogenetic distances.ResultsWe isolatedH. marinusBE01 from an estuary in Rhode Island usingVibriofrom the same site as prey. Small, fast-moving attack phase BE01 cells attach to and invade prey cells, consistent with the intraperiplasmic predation strategy ofH. marinustype strain SJ. BE01 is a prey generalist, forming plaques onVibriostrains from the estuary as well asPseudomonasfrom soil andE. coli. Genome analysis revealed that BE01 is very closely related to SJ, with extremely high conservation of gene order and amino acid sequences. Despite this similarity, we identified two regions of gene content difference that likely resulted from horizontal gene transfer. Analysis of modal codon usage frequencies supports the hypothesis that these regions were acquired from bacteria with different codon usage biases compared toHalobacteriovorax. In BE01, one of these regions includes genes associated with mobile genetic elements, such as a transposase not found in SJ and degraded remnants of an integrase occurring as a full-length gene in SJ. The corresponding region in SJ included unique mobile genetic element genes, such as a site-specific recombinase and bacteriophage-related genes not found in BE01. Acquired functions in BE01 include thedndoperon, which encodes a pathway for DNA modification that may protect DNA from nucleases, and a suite of genes involved in membrane synthesis and regulation of gene expression that was likely acquired from anotherHalobacteriovoraxlineage.ConclusionsOur results support previous observations thatHalobacteriovoraxprey on a broad range of Gram-negative bacteria. Genome analysis suggests strong selective pressure to maintain the genome in theH. marinuslineage represented by BE01 and SJ, although our results also provide further evidence that horizontal gene transfer plays an important role in genome evolution in predatory bacteria.

scholarly journals Antibacterial activity of ethanolic leaf extract of Aquilaria malaccensis against multidrug-resistant Gram-negative pathogen

Food Research ◽  
2020 ◽  
Vol 4 (6) ◽  
pp. 1962-1968
Author(s):  
N.I.M. Jihadi ◽  
Y.Z.H-Y. Hashim ◽  
N.A. Rahim ◽  
K.M. Kamal ◽  
N.M. Noor ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Leaf Extract ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Aquilaria Malaccensis ◽  
Crude Leaf Extract

The rapid emergence of resistant Gram-negative bacteria and the limited discovery of novel antibiotic is a global healthcare challenge. Many medicinal plants with potent bioactivities have been developed for the treatment of bacterial infections. Aquilaria malaccensis exhibits wide applications from perfumes and aromatic foods ingredients and great potential in medicines. In this study, crude leaf extract of A. malaccensis was evaluated for its antibacterial activity against several pathogenic Gram-negative bacteria. The leaves were processed and extracted by Soxhlet method using ethanol as the solvent. The antibacterial activity of the crude extract was tested by disc diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Acinetobacter baumannii (ATCC 19606), Klebsiella pneumoniae (ATCC 10031 and ATCC 700603) and Escherichia coli (ATCC 1129). Using the optimized method, the Soxhlet extract produced a yield of 178.41 mg/g. Treatment of the extract at 200 mg/mL displayed the largest inhibition zones of 14.0 mm and 9.7 mm against A. baumannii and K. pneumoniae ATCC 10031, respectively. In contrast, against E. coli and K. pneumoniae ATCC 700603, smaller zones of inhibitions of 3.3 mm were demonstrated. The MIC values of the extract were 32 mg/mL against A. baumannii and K. pneumoniae ATCC 10031 and 64 mg/mL against E. coli and K. pneumoniae ATCC 700603. The MBC values of the extract were consistent with the MIC values for all the bacteria investigated. Overall, this study was the first to show antibacterial activity of A. malaccensis leaves extract particularly against A. baumannii and K. pneumoniae and potentially develop for the treatment of resistant bacteria.

Characterizing and Overcoming Resistance to Aminomethylspectinomycins in Gram-negative Bacteria

2021 ◽  
Author(s):  
◽  
Nisha Das ◽  
Keyword(s):  
Small Molecule ◽  
Legionella Pneumophila ◽  
Bacterial Infections ◽  
Enzyme Assay ◽  
Bacterial Species ◽  
Enteric Bacteria ◽  
Response Analysis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli

Spectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3")(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to modify and inactivate amSPCs has been examined by two unique biochemical assays, including an agar-based enzyme assay. Binding of APH (9)-Ia and ANT (3")(9) to spectinomycin and amSPCs has been studied using Thermal Denaturation assay and MicroScale Thermophoresis (MST). The microbiological role of these enzymes has been examined by minimum inhibitory concentration (MIC) shifts using an arabinose inducible expression of APH (9)-Ia and ANT (3")(9) in E.coli K12 and JW ΔtolC strains. Our agar-based enzyme assay shows the inactivation of spectinomycin by APH(9)-Ia. Phosphorylated spectinomycin and adenylated spectinomycin products upon incubation with APH(9)-Ia and ANT(3",9), respectively, have been identified using MALDI-MS. APH(9)-Ia induction studies in E. coli tolC knock-out strains reveal a MIC increase against spectinomycin in the presence of 2% arabinose compared to no shift with amSPCs. ANT (3")(9) showed an increase in MIC against spectinomycin as well as amSPCs. In conclusion, amSPCs are not inactivated by APH (9)-Ia in vivo but are inactivated by ANT (3")(9). Most Gram-negative bacteria isolated in clinics possess one or more AMEs. By overcoming modification by AMEs, amSPCs can be a valuable tool in overcoming resistance in Gram-negative bacterial infections. We also conducted a high throughput screen of a polar small molecule library against two multi-drug resistant clinical isolates of Escherichia coli that encode aminoglycoside modifying enzyme for small molecule potentiators of amSPCs to yield 12 possible potentiating molecules that have been confirmed by dose-response analysis. Future work as a continuation of this project will involve further analysis of any existing synergy between the potentiating molecules and amSPCs and target validation of these potentiators.

Disinfection of Fruits with Activated Water

2019 ◽  
Vol 10 ◽  
pp. 1864-1872
Author(s):  
Prof. Teodora P. Popova
Keyword(s):  
Antimicrobial Activity ◽  
Aqueous Solutions ◽  
Antimicrobial Properties ◽  
The Other ◽  
Gram Negative Bacteria ◽  
High Antimicrobial Activity ◽  
Gram Negative ◽  
E Coli ◽  
Number Of Microorganisms ◽  
Lower Effect

The effect of ionized aqueous solutions (anolytes and catholyte) in the processing of fruits (cherries, morellos, and strawberries) for decontamination has been tested. Freshly prepared analytes and catholyte without the addition of salts were used, as well as stored for 7 months anolytes, prepared with 0.5% NaCl and a combination of 0.5% NaCl and 0.5% Na2CO3. The anolyte prepared with a combination of 0.5% NaCl and 0.5% Na2CO3, as well as the anolyte obtained with 0.5% NaCl, exhibit high antimicrobial activity against the surface microflora of strawberries, cherries, and sour cherries. They inactivate E. coli for 15 minutes. The other species of the fam. Enterobacteriaceae were also affected to the maximum extent, as is the total number of microorganisms, especially in cherries and sour cherries. Even stored for 7 months, they largely retain their antimicrobial properties. Anolyte and catholyte, obtained without the addition of salts, showed a lower effect on the total number of microorganisms, but had a significant effect on Gram-negative bacteria, and especially with regard to the sanitary indicative E. coli.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

Structure-Activity Relationship and Antimicrobial Evaluation of N-Phenylpyrazole Curcumin Derivatives

2020 ◽  
Vol 16 (4) ◽  
pp. 481-488
Author(s):  
Heli Sanghvi ◽  
Satyendra Mishra
Keyword(s):  
Antibacterial Activity ◽  
Gram Negative Bacteria ◽  
Pyrazole Derivatives ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Curcumin Derivatives ◽  
Structure Activity ◽  
Electron Donating Groups ◽  
Derivatives Of

Background: Curcumin, one of the most important pharmacologically significant natural products, has gained significant consideration among scientists for decades since its multipharmacological activities. 1, 3-Dicarbonyl moiety of curcumin was found to be accountable for the rapid degradation of curcumin molecule. The aim of present work is to replace 1, 3-dicarbonyl moiety of curcumin by pyrazole and phenylpyrazole derivatives with a view to improving its stability and to investigate the role of substitution in N-phenylpyrazole curcumin on its antibacterial activity against both Gram-positive as well as Gram-negative bacteria. Methods: Pyrazole derivatives of curcumin were prepared by heating curcumin with phenyhydrazine/ substituted phenyhydrazine derivatives in AcOH. The residue was purified by silica gel column chromatography. Structures of purified compounds were confirmed by 1H NMR and Mass spectroscopy. The synthesized compounds were evaluated for their antibacterial activity by the microdilution broth susceptibility test method against gram positive (S. aureus) and gram negative (E. coli). Results: Effects of substitution in N-phenylpyrazole curcumin derivatives against S. aureus and E. coli were studied. The most active N-(3-Nitrophenylpyrazole) curcumin (12) exhibits twenty-fold more potency against S. aureus (MIC: 10μg/mL)) and N-(2-Fluoroophenylpyrazole) curcumin (5) fivefold more potency against E. coli (MIC; 50 μg/mL) than N-phenylpyrazole curcumin (4). Whereas, a remarkable decline in anti-bacterial activity against S. aureus and E. coli was observed when electron donating groups were incorporated in N-phenylpyrazole curcumin (4). Comparative studies of synthesized compounds suggest the effects of electron withdrawing and electron donating groups on unsubstituted phenylpyrazole curcumin (4). Conclusion: The structure-activity relationship (SAR) results indicated that the electron withdrawing and electron donating at N-phenylpyrazole curcumin played key roles for their bacterial inhibitory effects. The results of the antibacterial evaluation showed that the synthesized pyrazole derivatives of curcumin displayed moderate to very high activity in S. aureus. In conclusion, the series of novel curcumin derivatives were designed, synthesized and tested for their antibacterial activities against S. aureus and E. coli. Among them, N-(3-Nitrophenylpyrazole curcumin; 12) was most active against S. aureus (Gram-positive) and N-(2-Fluoroophenylpyrazole) curcumin (5) against E. coli (Gram-negative) bacteria.

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