scholarly journals Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii

2018 ◽  
Vol 19 (10) ◽  
pp. 3041 ◽  
Author(s):  
Min Kim ◽  
Na Kang ◽  
Su Ko ◽  
Jonggwan Park ◽  
Eunji Park ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
High Stability ◽  
Therapeutic Agents ◽  
Antibiofilm Activity ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Biofilm Inhibition ◽  
Antibiotic Resistant

Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted to investigate the antibacterial activity of magainin 2 against Acinetobacter baumannii. Magainin 2 showed excellent antibacterial activity against A. baumannii strains and high stability at physiological salt concentrations. This peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity. Biofilm inhibition and elimination were significantly induced in all A. baumannii strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the bacterial outer and inner membranes. Collectively, these results suggest that magainin 2 is an effective antimicrobial and antibiofilm agent against A. baumannii strains.

scholarly journals Lysophosphatidylcholine Potentiates Antibacterial Activity of Polymyxin B

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Jitender Yadav ◽  
Sana Ismaeel ◽  
Ayub Qadri
Keyword(s):  
Antibacterial Activity ◽  
Polymyxin B ◽  
Resistant Bacteria ◽  
Bacterial Membrane ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Drug Resistant Bacteria

ABSTRACT Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of Salmonella and at least two other Gram-negative bacteria in vitro. This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

scholarly journals Enhanced Antibacterial Activity of Meropenem against Extensively Drug-Resistant Acinetobacter baumannii by Myrtaceae Plant Extracts

2020 ◽  
Vol 17 (11) ◽  
pp. 1168-1176
Author(s):  
Dennapa SAELOH ◽  
Monton VISUTTHI ◽  
Marisa LEEHA ◽  
Surasak LIMSUWAN ◽  
Supayang Piyawan VORAVUTHIKUNCHAI
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Drug Resistant ◽  
Microdilution Method ◽  
Extensively Drug Resistant ◽  
Resistant Phenotype ◽  
Bacterial Growth Inhibition ◽  
Mic Value

Acinetobacter baumannii (A. baumannii) has been known as a major cause of nosocomial bacterial infections worldwide. The bacteria are increasingly associated with a broad spectrum of antibiotic resistance, and this has become a widespread concern in a variety of hospitals.Antibiotic development and alternative treatment have become priorities for the treatment of bacterial infections.This study investigated the efficacy of meropenem in combination with five ethanolic extracts of plants in Myrtaceae against extensively drug-resistant (XDR) A. baumannii. The resistant phenotype was previously determined by microdilution method. XDR-A. baumannii strains showed resistance to meropenem with the minimum inhibitory concentration (MIC) in a range of 16 - 128 µg/mL, whereas the MIC value of all extracts, including Calistemon lancealatus, Eucalyptus citridora, Rhodomytus tomentasa, Syzygium cumini, and Xanthortemon chrysanthus, was over 1,000 µg/mL. Interestingly, all extracts potentiated the activity of the antibiotic by reducing the MIC values of the antibiotic. Xanthortemon chrysanthus extract displayed excellent synergism against the bacteria by decreasing the MIC value of the drug greater than 8-fold. In addition, the extract, at concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL, obviously increased the inhibitory effect of meropenem (1/4´MIC) against A. baumannii. The percentage of bacterial growth inhibition by combination was 87.9, 88.8, 91.8, 93.6, 99.9, and 100, respectively. The results supported that the extract could improve the activity of ineffective antibiotics against drug-resistant pathogens.Therefore, the findings may serve as therapeutic options for XDR-A. baumannii infections in the future.

scholarly journals Antibacterial Activity of Prismatomeris tetrandra K. Schum Root Extract against Antibiotic Resistance Bacteria

2018 ◽  
Vol 16 (5) ◽  
pp. 341-348
Author(s):  
On-Anong SOMSAP
Keyword(s):  
Antibacterial Activity ◽  
Antibiotic Resistance ◽  
Culture Broth ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
Root Extract ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Positive Bacteria ◽  
Colony Forming Units

Antibiotic resistance bacteria has become an increasing problem now today due to many factors. This study investigates the efficacy of Prismatomeris tetrandra K. Schum root extract as a new source of antibacterial activity for antibiotic resistant bacteria using agar well diffusion method. The results showed that S. aureus TISTR517 exhibited more sensitivity to P. tetrandra K. Schum root extract than other Gram-positive bacteria indicator strains. On the other hand, Gram-negative bacteria exhibited resistance to P. tetrandra K. Schum root extract. The study further showed the activity between P. tetrandra K. Schum root extract and gentamycin (10 µg), it revealed that MRSA142 was resistant to gentamycin (10µg) but sensitive to P. tetrandra K. Schum root extract. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was evaluated by using S. aureus TISTR517 and MRSA142 as indicator strains. The MIC value was 0.59 mg/mL and 1.17 mg/mL for S. aureus TISTR517 and MRSA142, respectively. MBC assay demonstrated that the MBC value was 9.75 mg/mL and 150 mg/mL for S. aureus TISTR517 and MRSA142 respectively. The mode of action was investigated with the presence of P. tetrandra K. Schum root extract in the culture broth. The action of P. tetrandra K. Schum root extract was revealed of bacteriostatic activity due to the Optical density (OD) at 600 nm and Colony-Forming Units (CFU) of indicator strains were continuously decreased.

scholarly journals Antibacterial activity of Taxodium ascendens Diterpenes against Methicillin-resistant Staphylococcus aureus

2014 ◽  
Vol 9 (8) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Courtney M. Starks ◽  
Vanessa L. Norman ◽  
Russell B. Williams ◽  
Matt G. Goering ◽  
Stephanie M. Rice ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Methicillin Resistant

One new and seven known diterpenes were identified from an antibacterial chromatographic fraction of Taxodium ascendens. Of these, demethylcryptojaponol (2), 6-hydroxysalvinolone (3), hydroxyferruginol (4), and hinokiol (5) demonstrated potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). These compounds represent a class of synthetically accessible compounds that could be further developed for treatment of drug-resistant bacterial infections.

scholarly journals 694. In vitro Antibacterial Activity of Sulbactam–Durlobactam (ETX2514SUL) Against 121 Recent Acinetobacter baumannii Isolated from Patients in India

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S314
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Tarun Mathur ◽  
Ian Morrissey
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Package Insert ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
In Vitro Antibacterial Activity ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant Acinetobacter baumannii is increasing at an alarming rate in Southeast Asia and other parts of the world. Sulbactam (SUL) has intrinsic antibacterial activity against A. baumannii; however, the prevalence of β-lactamases in this species has limited its therapeutic use. Durlobactam (ETX2514, DUR) is a novel β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases. DUR restores SUL in vitro activity against multidrug-resistant A. baumannii. Against >3,600 globally diverse, clinical isolates from 2012–2017, addition of 4 mg/L DUR reduced the SUL MIC90 from >32 to 2 mg/L. SUL-DUR is currently in Phase 3 clinical development for the treatment of infections caused by carbapenem-resistant Acinetobacter spp.The goal of this study was to determine the activity of SUL-DUR and comparator antibiotics (amikacin (AMK), ampicillin-sulbactam (AMP-SUL), cefoperazone-sulbactam (CFP-SUL) and meropenem (MEM)) against A. baumannii isolated from hospitalized patients in India. Methods A total of 121 clinical A. baumannii isolates from multiple hospital settings and infection sources were collected between 2016–2019 from six geographically diverse hospitals in India. Species identification was performed by MALDI-TOF. Susceptibility of these isolates to SUL-DUR (10µg/10µg) and comparator antibiotics was determined by disk diffusion using CLSI methodology and interpretive criteria, except for CFP-SUL, for which resistance was defined using breakpoints from the CFP-SUL package insert. Results As shown in Table 1, resistance of this collection of isolates to marketed agents was extremely high. In contrast, based on preliminary breakpoint criteria, only 11.5% of isolates were resistant to SUL-DUR. Conclusion The in vitro antibacterial activity of SUL-DUR was significantly more potent than comparator agents against multidrug-resistant A. baumannii isolates collected from diverse sites in India. These data support the continued development of SUL-DUR for the treatment of antibiotic-resistant infections caused by A. baumannii. Disclosures All authors: No reported disclosures.

scholarly journals N-alkylimidazolium Salts Functionalized with p-Coumaric and Cinnamic Acid: A Study of Their Antimicrobial and Antibiofilm Effects

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3484
Author(s):  
Oscar Forero-Doria ◽  
Ramiro Araya-Maturana ◽  
Anggela Barrientos-Retamal ◽  
Luis Morales-Quintana ◽  
Luis Guzmán
Keyword(s):  
Antibacterial Activity ◽  
Cinnamic Acid ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Good Alternative ◽  
Antibiofilm Activity ◽  
Coumaric Acid ◽  
Cinnamic Acids ◽  
Gram Positive Bacteria ◽  
Therapeutic Alternatives

The bacterial resistance to antibiotics has compromised the therapies used for bacterial infections. Nowadays, many strategies are being carried out to address this problem. Among them, the use of natural compounds like cinnamic and p-coumaric acids stands out. Nevertheless, their utilization is limited because of their unfavorable physicochemical properties. Due to the lack of new therapeutic alternatives for bacterial infections, novel strategies have emerged, such as the use of ionic liquids; given that they can show a broad spectrum of antibacterial activity, this is why we herein report the antibacterial and antibiofilm activity of a series of N-alkylimidazolium salts functionalized with p-coumaric and cinnamic acids. The results from this study showed better antibacterial activity against Gram-positive bacteria, with a predominance of the salts derived from coumaric acid and a correlation with the chain length. Additionally, a lower efficacy was observed in the inhibition of biofilm formation, highlighting the antibiofilm activity against Staphylococcus aureus, which decreased the production of the biofilm by 52% over the control. In conclusion, we suggest that the salts derived from p-coumaric acid are good alternatives as antibacterial compounds. Meanwhile, the salt derived from cinnamic acid could be a good alternative as an antibiofilm compound.

scholarly journals Removing Legionella pneumophila and biofilms from water supply systems using plant essential oils

2017 ◽  
Vol 7 (1) ◽  
pp. 67-73
Author(s):  
Ozgur Ceylan ◽  
Bulent Turasay
Keyword(s):  
Antibacterial Activity ◽  
Essential Oils ◽  
Legionella Pneumophila ◽  
Biofilm Formation ◽  
Thymus Vulgaris ◽  
Water Supply Systems ◽  
Antibiofilm Activity ◽  
Biofilm Inhibition ◽  
Thyme Oil ◽  
Lemon Oil

Antibacterial and antibiofilm activities of sage (Salvia officinalis), thyme (Thymus vulgaris), peppermint (Mentha x piperita) and lemon (Citrus limonum) essential oils (EOs), supplied as commercial preparations, were investigated on Legionella pneumophila. Results showed that all EOs had antibacterial activity. Lemon oil demonstrated the best activity, with minimum inhibition concentration (MIC) and minimum bactericidal concentration values detected as 0.83–1.25 and 1.25–3.75 μL/mL, respectively. Antibiofilm activities of EOs were studied in two ways: (1) inhibition of biofilm formation at subMIC concentrations; and (2) eradication of preformed biofilms at MIC and subMIC concentrations. The highest biofilm inhibition values were 63.3, 45.5, 35.6 and 23%, and the highest eradication values were 34.2, 16.7, 39.4 and 31.9% for lemon oil, peppermint oil, sage oil and thyme oil, respectively. Lemon oil was detected to have the highest antibiofilm activity, as with antibacterial activity. The minimum antibiofilm activity was found for thyme oil. For all the EOs, the inhibition of biofilm formation was higher than the eradication of preformed biofilms at the same concentrations. The results suggested that EOs of lemon, peppermint, sage and thyme had the potential for being used in the removal of L. pneumophila from potable water systems, due to their antibacterial and antibiofilm activities.

scholarly journals Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Nadine Lemaître ◽  
Xiaofei Liang ◽  
Javaria Najeeb ◽  
Chul-Jin Lee ◽  
Marie Titecat ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Biosynthetic Pathway ◽  
Lipid A ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Bubonic Plague ◽  
Gram Negative ◽  
New Class

ABSTRACT The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of LpxC inhibitors against a wide variety of Gram-negative bacterial infections, including the most severe ones caused by Y. pestis and by multidrug-resistant and extensively drug-resistant carbapenemase-producing strains. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of LpxC inhibitors against a wide variety of Gram-negative bacterial infections, including the most severe ones caused by Y. pestis and by multidrug-resistant and extensively drug-resistant carbapenemase-producing strains.

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