scholarly journals A Chimeric Cationic Peptide Composed of Human β-Defensin 3 and Human β-Defensin 4 Exhibits Improved Antibacterial Activity and Salt Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjing Yu ◽  
Nianzhi Ning ◽  
Ying Xue ◽  
Yanyu Huang ◽  
Feng Guo ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
A549 Cells ◽  
Multidrug Resistant ◽  
Salt Resistance ◽  
High Salt ◽  
Resistant Isolate ◽  
Klebsiella Pneumonia ◽  
Staphyloccocus Aureus

Human beta-defensins (hBDs) play an important role in the host defense against various microbes, showing different levels of antibacterial activity and salt resistance in vitro. It is of interest to investigate whether can chimeric hBD analogs enhanced antibacterial activity and salt resistance. In this study, we designed a chimeric human defensin, named H4, by combining sequences of human beta-defensin-3 (hBD-3) and human beta-defensin-4 (hBD-4), then evaluated its antibacterial activity, salt resistance, and cytotoxic effects. The result showed that the antibacterial activity of H4 against most tested strains, including Klebsiella pneumonia, Enterococcus faecalis, Staphyloccocus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumannii was significantly improved compared to that of hBD-3 and hBD-4. Notably, H4 exhibited significantly better antibacterial activity against multidrug resistant isolate A. baumannii MDR-ZJ06 than commonly used antibiotics. Chimeric H4 still showed more than 80% antibacterial activity at high salt concentration (150 μM), which proves its good salt tolerance. The cytotoxic effect assay showed that the toxicity of H4 to Hela, Vero, A549 cells and erythrocytes at a low dose (<10 μg/ml) was similar to that of hBD-3 and hBD-4. In conclusion, given its broad spectrum of antibacterial activity and high salt resistance, chimeric H4 could serve as a promising template for new therapeutic antimicrobial agents.

scholarly journals N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation

2020 ◽  
Vol 13 (12) ◽  
pp. 469
Author(s):  
Sergey N. Lavrenov ◽  
Elena B. Isakova ◽  
Alexey A. Panov ◽  
Alexander Y. Simonov ◽  
Viktor V. Tatarskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
Carbon Chain ◽  
Biological Evaluation ◽  
Carbon Chain Length ◽  
Klebsiella Pneumonia ◽  
Moderate Activity ◽  
Bacterial Strains ◽  
Reference Drug

The wide spread of pathogens resistance requires the development of new antimicrobial agents capable of overcoming drug resistance. The main objective of the study is to elucidate the effect of substitutions in tris(1H-indol-3-yl)methylium derivatives on their antibacterial activity and toxicity to human cells. A series of new compounds were synthesized and tested. Their antibacterial activity in vitro was performed on 12 bacterial strains, including drug resistant strains, that were clinical isolates or collection strains. The cytotoxic effect of the compounds was determined using an test with HPF-hTERT (human postnatal fibroblasts, immortalized with hTERT) cells. The activity of the obtained compounds depended on the carbon chain length. Derivatives with C5–C6 chains were more active. The minimum inhibitory concentration (MIC) of the most active compound on Gram-positive bacteria, including MRSA, was 0.5 μg/mL. Compounds with C5–C6 chains also revealed high activity against Staphylococcus epidermidis (1.0 and 0.5 μg/mL, respectively) and moderate activity against Gram-negative bacteria Escherichia coli (8 μg/mL) and Klebsiella pneumonia (2 and 8 μg/mL, respectively). However, they have no activity against Salmonella cholerasuis and Pseudomonas aeruginosa. The most active compounds revealed higher antibacterial activity on MRSA than the reference drug levofloxacin, and their ratio between antibacterial and cytotoxic activity exceeded 10 times. The data obtained provide a basis for further study of this promising group of substances.

scholarly journals Random Mutagenesis of theAspergillus oryzaeGenome Results in Fungal Antibacterial Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Cory A. Leonard ◽  
Stacy D. Brown ◽  
J. Russell Hayman
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Random Mutagenesis ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Antibacterial Compounds ◽  
Severe Infections

Multidrug-resistant bacteria cause severe infections in hospitals and communities. Development of new drugs to combat resistant microorganisms is needed. Natural products of microbial origin are the source of most currently available antibiotics. We hypothesized that random mutagenesis ofAspergillus oryzaewould result in secretion of antibacterial compounds. To address this hypothesis, we developed a screen to identify individualA. oryzaemutants that inhibit the growth of Methicillin-resistantStaphylococcus aureus(MRSA)in vitro. To randomly generateA. oryzaemutant strains, spores were treated with ethyl methanesulfonate (EMS). Over 3000 EMS-treatedA. oryzaecultures were tested in the screen, and one isolate, CAL220, exhibited altered morphology and antibacterial activity. Culture supernatant from this isolate showed antibacterial activity against Methicillin-sensitiveStaphylococcus aureus, MRSA, andPseudomonas aeruginosa, but notKlebsiella pneumoniaorProteus vulgaris. The results of this study support our hypothesis and suggest that the screen used is sufficient and appropriate to detect secreted antibacterial fungal compounds resulting from mutagenesis ofA. oryzae. Because the genome ofA. oryzaehas been sequenced and systems are available for genetic transformation of this organism, targeted as well as random mutations may be introduced to facilitate the discovery of novel antibacterial compounds using this system.

scholarly journals 1293. Sulbactam-durlobactam is active against recent, multi-drug resistant Acinetobacter baumannii clinical isolates from the Middle East

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S662-S662
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Samir Moussa ◽  
Meredith Hackel
Keyword(s):  
Antibacterial Activity ◽  
Middle East ◽  
Acinetobacter Baumannii ◽  
United Arab Emirates ◽  
Blood Stream ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Surveillance Systems ◽  
Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (Ab) is increasing at an alarming rate in certain regions of the world, including the Middle East. Sulbactam (SUL) has intrinsic antibacterial activity against Ab; however, the prevalence of β-lactamases in Ab has limited its therapeutic utility. Durlobactam (DUR, formerly ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases that restores SUL activity in vitro against MDR Ab. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, that is currently in Phase 3 clinical development. In global surveillance studies of >3600 isolates from 2012-2017, the MIC90 of SUL-DUR was 2 mg/L. Although surveillance systems to monitor MDR infections in the Middle East are currently being established, quantitative, prevalence-based data are not yet available. Therefore, the potency of SUL-DUR was determined against 190 recent, diverse Ab clinical isolates from this region. Methods 190 Ab isolates were collected between 2016 - 2018 from medical centers located in Israel (N = 47), Jordan (N = 36), Qatar (N = 13), Kuwait (N = 42), Lebanon (N = 8), Saudi Arabia (N = 24) and United Arab Emirates (N = 20). Seventy-five percent and 20.5% of these isolates were from respiratory and blood stream infections, respectively. Susceptibility to SUL-DUR and comparator agents was performed according to CLSI guidelines, and data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 86% carbapenem-resistant and 90% sulbactam-resistant (based on a breakpoint of 4 mg/L). The addition of SUL-DUR (fixed at 4 mg/L) decreased the sulbactam MIC90 from 64 mg/L to 4 mg/L. Only 3 isolates (1.6%) had SUL-DUR MIC values of > 4 mg/L. This potency was consistent across countries, sources of infection and subsets of resistance phenotypes. Conclusion SUL-DUR demonstrated potent antibacterial activity against recent clinical isolates of Ab from the Middle East, including MDR isolates. These data support the global development of SUL-DUR for the treatment of MDR Ab infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee) Sarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee)

scholarly journals An In Vitro Study on the Antimicrobial Properties of Essential Oil Modified Resin Composite against Oral Pathogens

Materials ◽  
2020 ◽  
Vol 13 (19) ◽  
pp. 4383
Author(s):  
Barbara Lapinska ◽  
Aleksandra Szram ◽  
Beata Zarzycka ◽  
Janina Grzegorczyk ◽  
Louis Hardan ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Antimicrobial Agents ◽  
Resin Composite ◽  
Antimicrobial Properties ◽  
In Vitro Study ◽  
Diffusion Method ◽  
Oral Pathogens

Modifying the composition of dental restorative materials with antimicrobial agents might induce their antibacterial potential against cariogenic bacteria, e.g., S.mutans and L.acidophilus, as well as antifungal effect on C.albicans that are major oral pathogens. Essential oils (EOs) are widely known for antimicrobial activity and are successfully used in dental industry. The study aimed at evaluating antibacterial and antifungal activity of EOs and composite resin material (CR) modified with EO against oral pathogens. Ten EOs (i.e., anise, cinnamon, citronella, clove, geranium, lavender, limette, mint, rosemary thyme) were tested using agar diffusion method. Cinnamon and thyme EOs showed significantly highest antibacterial activity against S.mutans and L.acidophilus among all tested EOs. Anise and limette EOs showed no antibacterial activity against S.mutans. All tested EOs exhibited antifungal activity against C.albicans, whereas cinnamon EO showed significantly highest and limette EO significantly lowest activity. Next, 1, 2 or 5 µL of cinnamon EO was introduced into 2 g of CR and microbiologically tested. The modified CR showed higher antimicrobial activity in comparison to unmodified one. CR containing 2 µL of EO showed the best antimicrobial properties against S.mutans and C.albicans, while CR modified with 1 µL of EO showed the best antimicrobial properties against L.acidophilus.

scholarly journals The Oxazolidinone Linezolid Inhibits Initiation of Protein Synthesis in Bacteria

1998 ◽  
Vol 42 (12) ◽  
pp. 3251-3255 ◽  
Author(s):  
Steve M. Swaney ◽  
Hiroyuki Aoki ◽  
M. Clelia Ganoza ◽  
Dean L. Shinabarger
Keyword(s):  
Protein Synthesis ◽  
Complex Formation ◽  
Antimicrobial Agents ◽  
Ribosomal Subunit ◽  
Multidrug Resistant ◽  
Binary Complex ◽  
Initiation Complex ◽  
Ribosomal Subunits ◽  
Bacterial Translation

ABSTRACT The oxazolidinones represent a new class of antimicrobial agents which are active against multidrug-resistant staphylococci, streptococci, and enterococci. Previous studies have demonstrated that oxazolidinones inhibit bacterial translation in vitro at a step preceding elongation but after the charging ofN-formylmethionine to the initiator tRNA molecule. The event that occurs between these two steps is termed initiation. Initiation of protein synthesis requires the simultaneous presence of N-formylmethionine-tRNA, the 30S ribosomal subunit, mRNA, GTP, and the initiation factors IF1, IF2, and IF3. An initiation complex assay measuring the binding of [3H]N-formylmethionyl-tRNA to ribosomes in response to mRNA binding was used in order to investigate the mechanism of oxazolidinone action. Linezolid inhibited initiation complex formation with either the 30S or the 70S ribosomal subunits fromEscherichia coli. In addition, complex formation withStaphylococcus aureus 70S tight-couple ribosomes was inhibited by linezolid. Linezolid did not inhibit the independent binding of either mRNA or N-formylmethionyl-tRNA toE. coli 30S ribosomal subunits, nor did it prevent the formation of the IF2–N-formylmethionyl-tRNA binary complex. The results demonstrate that oxazolidinones inhibit the formation of the initiation complex in bacterial translation systems by preventing formation of theN-formylmethionyl-tRNA–ribosome–mRNA ternary complex.

scholarly journals Assessment of Microbial Load of Un-pasteurized Fruit Juices and in vitro Antibacterial Potential of Honey Against Bacterial Isolates

2015 ◽  
Vol 9 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Muhammad Naeem Iqbal ◽  
Aftab Ahmad Anjum ◽  
Muhammad Asad Ali ◽  
Firasat Hussain ◽  
Shahzad Ali ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Viable Count ◽  
Fruit Juices ◽  
Microbial Load ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Street Vendors ◽  
Permissible Limits ◽  
Development Of Resistance

The development of resistance in bacteria against commonly used antibiotics/drugs is of considerable medical significance. Aim of this study was to determine the microbial load of un-pasteurized packed fruit juices sold in Lahore city and to determine antibacterial activity of five different honey samples against isolated bacteria. Unpasteurized fruit juice samples (n=60) were collected from street vendors. All the samples were subjected to Total viable count (TVC), Staphylococcal count (SC) and Coliform count (CC). One hundred and ten strains of bacteria were isolated from various fruit juices and identified on the basis of cultural characters, morphology and biochemical characters. Mean TVCs, SCs and CCs of juices (6.80±1.91, 5.45±1.06 and 3.25±1.25 log10 CFU/ml respectively) were non-significant with standard permissible limits (p<0.05). Among all the fruit juices, 66.66% of samples had TVC more than 4 log10 CFU/ml, 51.66% of samples had SC more than 3 log10 CFU/ml and 46.66% of samples had CC more than 2 log10 CFU/ml. Among the bacillus isolates purified, were Bacillus alvei, Bacillus subtilis, Bacillus polymyxa, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli and Enterobecter. All five different types of honey samples used in this study showed antibacterial activity against B. alvei, B. polymyxa, B. subtilis and S. aureus and no activity against P. aeruginosa, K. pneumonia, Enterobecter and E. coli. It is concluded that microbial load in unpasteurized fruit juices is significantly higher than standard permissible limits which insinuates its possible role in spoilage and food borne illnesses. Periodic monitoring of packed fruit juices should be carried out to make them safe for consumption. Honey can be used as an alternative for treatment of various infections, especially those caused by antibiotic resistant bacteria.

scholarly journals Formulation and Evaluation of Antibacterial Creams and Gels Containing Metal Ions for Topical Application

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mei X. Chen ◽  
Kenneth S. Alexander ◽  
Gabriella Baki
Keyword(s):  
Antibacterial Activity ◽  
Metal Ions ◽  
Copper Sulfate ◽  
Zinc Sulfate ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Minimum Effective Concentration ◽  
Organoleptic Characteristics

Background. Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. Objective. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the in vitro antibacterial activity of these metal ions in the formulations. Method. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. Conclusions. This study evaluated and confirmed the synergistic in vitro antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels.

scholarly journals Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae

2021 ◽  
Vol 11 ◽  
Author(s):  
Na Li ◽  
Yigang Zeng ◽  
Rong Bao ◽  
Tongyu Zhu ◽  
Demeng Tan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
S1 Nuclease ◽  
Isolation And Characterization ◽  
Comprehensive Knowledge ◽  
Future Challenges ◽  
Lactamase Gene

Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (blaKPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant K. pneumoniae isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of Podoviridae were isolated and characterized to evaluate the application of lytic phages against the MDR K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.

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