scholarly journals Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5035
Author(s):  
Sandra Patricia Rivera-Sánchez ◽  
Helen Astrid Agudelo-Góngora ◽  
José Oñate-Garzón ◽  
Liliana Janeth Flórez-Elvira ◽  
Adriana Correa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Genomic Dna ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Bacterial Strains ◽  
Scanning Calorimetry ◽  
Cationic Antimicrobial Peptide ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Membrane Models

Antimicrobial resistance reduces the efficacy of antibiotics. Infections caused by multidrug-resistant (MDR), Gram-negative bacterial strains, such as Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are a serious threat to global health. However, cationic antimicrobial peptides (CAMPs) are promising as an alternative therapeutic strategy against MDR strains. In this study, the inhibitory activity of a cationic peptide, derived from cecropin D-like (ΔM2), against MDRKp and MDRPa clinical isolates, and its interaction with membrane models and bacterial genomic DNA were evaluated. In vitro antibacterial activity was determined using the broth microdilution test, whereas interactions with lipids and DNA were studied by differential scanning calorimetry and electronic absorption, respectively. A strong bactericidal effect of ΔM2 against MDR strains, with minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) between 4 and 16 μg/mL, was observed. The peptide had a pronounced effect on the thermotropic behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane models that mimic bacterial membranes. Finally, the interaction between the peptide and genomic DNA (gDNA) showed a hyperchromic effect, which indicates that ΔM2 can denature bacterial DNA strands via the grooves.

scholarly journals A Novel Cecropin D-Derived Short Cationic Antimicrobial Peptide Exhibits Antibacterial Activity Against Wild-Type and Multidrug-Resistant Strains of Klebsiella pneumoniae and Pseudomonas aeruginosa

2020 ◽  
Vol 16 ◽  
pp. 117693432093626
Author(s):  
Iván Darío Ocampo-Ibáñez ◽  
Yamil Liscano ◽  
Sandra Patricia Rivera-Sánchez ◽  
José Oñate-Garzón ◽  
Ashley Dayan Lugo-Guevara ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Health Concern ◽  
Wild Type ◽  
Cationic Antimicrobial Peptide ◽  
Promising Alternative ◽  
Resistant Strains

Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae are a serious worldwide public health concern due to the ineffectiveness of empirical antibiotic therapy. Therefore, research and the development of new antibiotic alternatives are urgently needed to control these bacteria. The use of cationic antimicrobial peptides (CAMPs) is a promising candidate alternative therapeutic strategy to antibiotics because they exhibit antibacterial activity against both antibiotic susceptible and MDR strains. In this study, we aimed to investigate the in vitro antibacterial effect of a short synthetic CAMP derived from the ΔM2 analog of Cec D-like (CAMP-CecD) against clinical isolates of K pneumoniae (n = 30) and P aeruginosa (n = 30), as well as its hemolytic activity. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of CAMP-CecD against wild-type and MDR strains were determined by the broth microdilution test. In addition, an in silico molecular dynamic simulation was performed to predict the interaction between CAMP-CecD and membrane models of K pneumoniae and P aeruginosa. The results revealed a bactericidal effect of CAMP-CecD against both wild-type and resistant strains, but MDR P aeruginosa showed higher susceptibility to this peptide with MIC values between 32 and >256 μg/mL. CAMP-CecD showed higher stability in the P aeruginosa membrane model compared with the K pneumoniae model due to the greater number of noncovalent interactions with phospholipid 1-Palmitoyl-2-oleyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG). This may be related to the boosted effectiveness of the peptide against P aeruginosa clinical isolates. Given the antibacterial activity of CAMP-CecD against wild-type and MDR clinical isolates of P aeruginosa and K pneumoniae and its nonhemolytic effects on human erythrocytes, CAMP-CecD may be a promising alternative to conventional antibiotics.

scholarly journals CHLOROFORM FRACTION OF PARKIA JAVANICA BARK POSSESSES ANTIBACTERIAL ACTIVITY AGAINST MULTIDRUG RESISTANT GRAM NEGATIVE BACTERIA PREDOMINANTLY FOUND IN SKIN WOUND

2018 ◽  
Vol 8 (5) ◽  
pp. 184-189
Author(s):  
S Saha ◽  
P Karmakar ◽  
Samir Kumar Sil
Keyword(s):  
Antibacterial Activity ◽  
Cell Damage ◽  
Multidrug Resistant ◽  
Skin Wound ◽  
Lag Phase ◽  
Klebsiella Pneumonia ◽  
Chloroform Fraction ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Antimicrobial Substances

Aim: To evaluate the antibacterial activity of Parkia javanica against gram negative MDR bacterial strains which are predominantly found in skin wound. Methods: The 5 different solvent fractions of Parkia javanica were screened for antibacterial activity against gram negative multi drug resistant bacterial strains namely Enterobacter aerugenes, Pseudomonas aeruginosa and Klebsiella pneumonia by serial dilution technique. Growth kinetics study was performed and percentage of ROS production was measured by NBT reduction assay. Results: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were obtained with a range of IC100 0.08-0.31 mg/ml in case of MDR bacterial strains. The lag phase of all extract treated bacteria is extended compared to untreated cells. The normalized % of ROS is increased in presence of Parkia javanica extract. Conclusions: This study suggests that, chloroform fraction of Parkia javanica possesses promising antimicrobial substances which are having activity against MDR bacterial strains and ROS induced bacterial cell damage could be the possible mediator of its antimicrobial activity. Keywords:   Parkia javanica, antibacterial activity, MDR bacterial strains, growth curve, ROS.

scholarly journals ANTIBACTERIAL ACTIVITY OF FOMITOPSIS BETULINA CULTURAL LIQUID

2019 ◽  
Vol 6 ◽  
pp. 10-16 ◽  
Author(s):  
Tetiana Krupodorova ◽  
Victor Barshteyn ◽  
Elena Pokas
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Clinical Isolates ◽  
Bacterial Strains ◽  
Bacterial Diseases ◽  
E Coli ◽  
Pharmaceutical Industries ◽  
Fomitopsis Betulina

The antibacterial activity of Fomitopsis betulina cultural liquid (native, native concentrated, lyophilized, dried) against standard bacteria (Escherichia coli АТСС 25922, Pseudomonas aeruginosa АТСС 27853, Staphylococcus aureus АТСС 25923), and clinical isolates (Acinetobacter baumannii 50/1496 MBL, A. baumannii 88/2995 MBL, E. coli 116/3196 KPC, Klebsiella pneumoniae 6/509 ESBL, AmpC, KPC, P. aeruginosa 99/3066 MBL, P. aeruginosa 125/3343 MBL, S. haemoliticus 22/824 MRSA, S. aureus 134/3569 MRCNS) has been evaluated by the serial dilutions method. The antibacterial activity of F. betulina against S. haemoliticus and A. baumannii has been found for the first time. All samples of F. betulina cultural liquid demonstrated the inhibitory effect against standard bacterial strains at the minimum bactericidal concentration (MBC) ranging from >2.0 up to 18.75 mg/ml, and against multidrug-resistant clinical isolates with MBC from 7.8 up to 48.42 mg/ml. The dried F. betulina cultural liquid showed the highest antimicrobial activity against standard bacteria and clinical isolates, except A. baumannii 50/1496 MBL, while native concentrated cultural liquid was the most effective against this pathogen. The study showed that the antibacterial activity of the cultural liquid of F. betulina was improved by concentration and drying. The results obtained indicate that F. betulina cultural liquid contains alternative antimicrobial agents, useful for the treatment of bacterial diseases and might be a perspective substance for the pharmaceutical industries

scholarly journals Gram-scale synthesis of splat-shaped Ag–TiO2 nanocomposites for enhanced antimicrobial properties

2020 ◽  
Vol 11 ◽  
pp. 1119-1125
Author(s):  
Mohammad Jaber ◽  
Asim Mushtaq ◽  
Kebiao Zhang ◽  
Jindan Wu ◽  
Dandan Luo ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Inhibition Zone ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Negative ◽  
E Coli ◽  
Contagious Diseases ◽  
Good Biocompatibility

The control over contagious diseases caused by pathogenic organisms has become a serious health issue. The extensive usage of antibiotics has led to the development of multidrug-resistant bacterial strains. In this regard, metal-oxide-based antibacterial nanomaterials have received potential research interest due to the efficient prevention of microorganism growth. In this study, splat-shaped Ag–TiO2 nanocomposites (NCs) were synthesized on the gram scale and the enhanced antibacterial properties of TiO2 in the presence of silver were examined. The formation of Ag–TiO2 NCs was analyzed through various characterization techniques. The cell viability experimental results demonstrated that the Ag–TiO2 NCs have good biocompatibility. The antibacterial activity of the prepared Ag–TiO2 NCs was tested against the Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacterial strains. The Ag–TiO2 NCs exhibited promising and superior antibacterial properties compared to TiO2 nanospheres as confirmed by the bacterial growth and inhibition zone. The improvement in the antibacterial activity was attributed to the synergistic effect of the hybrid nature of TiO2 nanoparticles in the presence of Ag.

scholarly journals Broad-Spectrum Bactericidal Activity of a Synthetic Random Copolymer Based on 2-Methoxy-6-(4-Vinylbenzyloxy)-Benzylammonium Hydrochloride

2021 ◽  
Vol 22 (9) ◽  
pp. 5021
Author(s):  
Anna Maria Schito ◽  
Gabriela Piatti ◽  
Debora Caviglia ◽  
Guendalina Zuccari ◽  
Silvana Alfei
Keyword(s):  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Random Copolymer ◽  
Multidrug Resistant ◽  
Water Soluble ◽  
Ammonium Salts ◽  
Gram Negative ◽  
Minimal Inhibitory Concentrations ◽  
Bacterial Membranes ◽  
Different Strains

Low-molecular-weight organic ammonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Unfortunately, short-term functionality and high toxicity limit their clinical application. On the contrary, the equivalent macromolecular ammonium salts, derived from the polymerization of monomeric ammonium salts, have demonstrated improved antibacterial potency, a lower tendency to develop resistance, higher stability, long-term activity, and reduced toxicity. A water-soluble non-quaternary copolymeric ammonium salt (P7) was herein synthetized by copolymerizing 2-methoxy-6-(4-vinylbenzyloxy)-benzylammonium hydrochloride monomer with N, N-di-methyl-acrylamide. The antibacterial activity of P7 was assessed against several multidrug-resistant (MDR) clinical isolates of both Gram-positive and Gram-negative species. Except for colistin-resistant Pseudomonas aeruginosa, most isolates were susceptible to P7, also including some Gram-negative bacteria with a modified charge in the external membrane. P7 showed remarkable antibacterial activity against isolates of Enterococcus, Staphylococcus, Acinetobacter, and Pseudomonas, and on different strains of Escherichia coli and Stenotrophomonas maltophylia, regardless of their antibiotic resistance. The lowest minimal inhibitory concentrations (MICs) observed were 0.6–1.2 µM and the minimal bactericidal concentrations (MBC) were frequently overlapping with the MICs. In 24-h time–kill and turbidimetric studies, P7 displayed a rapid non-lytic bactericidal activity. P7 could therefore represent a novel and potent tool capable of counteracting infections sustained by several bacteria that are resistant to the presently available antibiotics.

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)

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