Activity of Antimicrobial Peptides and Ciprofloxacin against Pseudomonas aeruginosa Biofilms

Pseudomonas aeruginosa is increasingly resistant to conventional antibiotics, which can be compounded by the formation of biofilms on surfaces conferring additional resistance. P. aeruginosa was grown in sub-inhibitory concentrations of the antimicrobial peptides (AMPs) melimine and Mel4 or ciprofloxacin for 30 consecutive days to induce the development of resistance. Antibiofilm effect of AMPs and ciprofloxacin was evaluated using crystal violet and live/dead staining with confocal microscopy. Effect on the cell membrane of biofilm cells was evaluated using DiSC(3)-5 dye and release of intracellular ATP and DNA/RNA. The minimum inhibitory concentration (MIC) of ciprofloxacin increased 64-fold after 30 passages, but did not increase for melimine or Mel4. Ciprofloxacin could not inhibit biofilm formation of resistant cells at 4× MIC, but both AMPs reduced biofilms by >75% at 1× MIC. At 1× MIC, only the combination of either AMP with ciprofloxacin was able to significantly disrupt pre-formed biofilms (≥61%; p < 0.001). Only AMPs depolarized the cell membranes of biofilm cells at 1× MIC. At 1× MIC either AMP with ciprofloxacin released a significant amount of ATP (p < 0.04), but did not release DNA/RNA. AMPs do not easily induce resistance in P. aeruginosa and can be used in combination with ciprofloxacin to treat biofilm.

Download Full-text

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

Current Medicinal Chemistry ◽

10.2174/0929867325666180117142142 ◽

2018 ◽

Vol 25 (21) ◽

pp. 2503-2519 ◽

Cited By ~ 4

Author(s):

Anne Kokel ◽

Marianna Torok

Keyword(s):

Side Effects ◽

Antimicrobial Peptides ◽

Potential Drug ◽

Green Technologies ◽

Specific Antibodies ◽

Structural Modifications ◽

Drug Candidates ◽

Induce Resistance ◽

Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

Download Full-text

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200427090912 ◽

2020 ◽

Vol 20 (14) ◽

pp. 1264-1273 ◽

Cited By ~ 1

Author(s):

Bruno Casciaro ◽

Floriana Cappiello ◽

Walter Verrusio ◽

Mauro Cacciafesta ◽

Maria Luisa Mangoni

Keyword(s):

Antimicrobial Peptides ◽

Inhibitory Concentration ◽

Multidrug Resistant ◽

Mechanisms Of Action ◽

New Drugs ◽

Lead Compounds ◽

Bacterial Pathogenicity ◽

Growth Inhibitory ◽

Resistant Strains ◽

Conventional Antibiotics

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

Download Full-text

Physicochemical and antimicrobial assessment of Iranian Propolis gathered in Qazvin province

Functional Foods in Health and Disease ◽

10.31989/ffhd.v10i2.689 ◽

2020 ◽

Vol 10 (2) ◽

pp. 82

Author(s):

Fatemeh Samieerad ◽

Nematollah Gheibi

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Minimum Inhibitory Concentration ◽

Thin Layer ◽

Inhibitory Concentration ◽

Minimum Bactericidal Concentration ◽

Antibacterial Effect ◽

Ethanol Extract ◽

Standard Strain ◽

Layer Chromatography

Background: Propolis is one of the useful bee colony products that have been used in traditional medicine for centuries. In this study, the physicochemical characters and their antibacterial effect of Iranian Propolis collected from Qazvin province was assessed.Methods: In this study, Thin Layer Chromatography and Vacuum Liquid Chromatography to detect different compounds of the extract have been used. In the initial evaluation of Propolis extract, it was found that the extract includes variable compounds with different polarity; so, the initial classification of extract with different polarity solvents was essential. Finally, 0.1 gr hydro alcoholic Propolis was injected to the HPLC by ultrasound. The antibacterial effect of Iranian ethanol extract Propolis was measured using a microdilution method against Pseudomonas aeruginosa: P. aeruginosa and Staphylococcus aureus: S.aureus standard strains and the minimum bactericidal and inhibitory concentration were defined.Results: Primary analysis of the ethanol extract by analytical Thin Layer Chromatography, demonstrated the presence of flavonoid and phenol in it. Minimum inhibitory concentration and Minimum Bactericidal Concentration for Staphylococcus aureus: S.aureus standard strain was 2.5mg/ml. The same procedure was done for Pseudomonas aeruginosa: P. aeruginosa standard strain and the Minimum inhibitory concentration and Minimum Bactericidal Concentration were 50mg/ml of Propolis extracts. Conclusion: According to the results, the alcoholic extract of propolis from Qazvin province of Iran provides significant antimicrobial activity. Its powerful activity may be due to high total phenolic and flavonoid contents.Keywords: Iranian propolis, Antibacterial activity, Phenolic compounds, Flavonoid compound

Download Full-text

Antibacterial and Hemolytic Activity of Crotalus triseriatus and Crotalus ravus Venom

Animals ◽

10.3390/ani10020281 ◽

2020 ◽

Vol 10 (2) ◽

pp. 281

Author(s):

Adrian Zaragoza-Bastida ◽

Saudy Consepcion Flores-Aguilar ◽

Liliana Mireya Aguilar-Castro ◽

Ana Lizet Morales-Ubaldo ◽

Benjamín Valladares-Carranza ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibacterial Activity ◽

Minimum Inhibitory Concentration ◽

Hemolytic Activity ◽

Inhibitory Concentration ◽

Minimum Bactericidal Concentration ◽

The Other ◽

Medical Treatments ◽

First Time

Rattlesnakes have venoms with a complex toxin mixture comprised of polypeptides and proteins. Previous studies have shown that some of these polypeptides are of high value for the development of new medical treatments. The aim of the present study is to evaluate, in vitro, the antibacterial and hemolytic activity of Crotalus triseriatus and Crotalus ravus venoms. A direct field search was conducted to obtain Crotalus triseriatus and Crotalus ravus venom samples. These were evaluated to determine their antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa through the techniques of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Hemolytic activity was also determined. Antibacterial activity was determined for treatments (Crotalus triseriatus 2) CT2 and (Crotalus ravus 3) CR3, obtaining a Minimum Inhibitory Concentration of 50 µg/mL and a Minimum Bactericidal Concentration of 100 µg/mL against Pseudomonas aeruginosa. CT1 (Crotalus triseriatus 1), CT2, and CR3 presented hemolytic activity; on the other hand, Crotalus ravus 4 (CR4) did not show hemolytic activity. The results of the present study indicate for the first time that Crotalus triseriatus and Crotalus ravus venoms contain some bioactive compounds with bactericidal activity against Pseudomonas aeruginosa which could be used as alternative treatment in diseases caused by this pathogenic bacterium.

Download Full-text

Antimicrobial peptides and bacteriocins: alternatives to traditional antibiotics

Animal Health Research Reviews ◽

10.1017/s1466252308001497 ◽

2008 ◽

Vol 9 (2) ◽

pp. 227-235 ◽

Cited By ~ 143

Author(s):

Yongming Sang ◽

Frank Blecha

Keyword(s):

Antimicrobial Peptides ◽

Membrane Integrity ◽

Principal Component ◽

Protective Response ◽

Antimicrobial Drugs ◽

Induce Resistance ◽

Unicellular Organisms ◽

Conventional Antibiotics ◽

Multicellular Organisms ◽

Recent Attention

AbstractAntimicrobial peptides (AMPs) are ubiquitous, gene-encoded natural antibiotics that have gained recent attention in the search for new antimicrobials to combat infectious disease. In multicellular organisms, AMPs, such as defensins and cathelicidins, provide a coordinated protective response against infection and are a principal component of innate immunity in vertebrates. In unicellular organisms, AMPs, such as bacteriocins, function to suppress competitor species. Because many AMPs kill bacteria by disruption of membrane integrity and are thus thought to be less likely to induce resistance, AMPs are being extensively evaluated as novel antimicrobial drugs. This review summarizes and discusses the antibiotic properties of AMPs highlighting their potential as alternatives to conventional antibiotics.

Download Full-text

Serum Inhibitory and Bactericidal Activity of Ciprofloxacin following Intravenous Administration

DICP ◽

10.1177/106002808902300603 ◽

1989 ◽

Vol 23 (6) ◽

pp. 456-460

Author(s):

Michael N. Dudley ◽

Hilary D. Mandler ◽

Kenneth H. Mayer ◽

Stephen H. Zinner

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Minimum Inhibitory Concentration ◽

Bactericidal Activity ◽

Resistant Strain ◽

Inhibitory Concentration ◽

Minimum Bactericidal Concentration ◽

E Coli ◽

Dose Levels

Serum inhibitory and bactericidal titers were measured in nine healthy volunteers following single iv doses of ciprofloxacin 100, 150, and 200 mg. The median peak serum bactericidal titer (5 minutes following completion of a 30-minute infusion) against two highly susceptible strains of Escherichia coli ranged between 1:64 and 1:1024 and titers exceeded 1:8 for six hours for all dose levels. The bactericidal titers against two strains of Pseudomonas aeruginosa and a methicillin-resistant strain of Staphylococcus aureus were considerably lower, the median peak being 1:2 at all dose levels. Measured inhibitory and bactericidal titers at five minutes and one hour postinfusion were significantly greater than those predicted (measured serum ciprofloxacin concentration to minimum inhibitory concentration [MIC] or minimum bactericidal concentration [MBC]) for only one strain of E. coli. Intravenous doses of ciprofloxacin 100–200 mg produce high and sustained serum bactericidal titers against highly susceptible bacteria; considerably lower levels of activity are seen against bacteria having higher MICs and MBCs but still considered susceptible to the drug.

Download Full-text

In vitro Development of Resistance to Azithromycin in Pseudomonas aeruginosa

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v21i1.37904 ◽

2018 ◽

Vol 21 (1) ◽

pp. 42-46

Author(s):

Thanmin Jarana Thammi ◽

Md Masud Rana ◽

Farhanur Rahman ◽

Apu Banik ◽

Md Anwar Ul Islam

Keyword(s):

Pseudomonas Aeruginosa ◽

Inhibitory Concentration ◽

Bacterial Species ◽

Public Health Problem ◽

Pharmaceutical Journal ◽

Zone Of Inhibition ◽

Development Of Resistance ◽

Improper Use ◽

Vitro Development

Antimicrobial resistance has been considered as a growing public health problem all over the world. Due to improper use of antibiotics many bacterial species including the Pseudomonas aeruginosa become resistant. So, the objectives of this study were to determine the success or failure of antibiotic therapy. Tests were performed in vitro and measured the growth response of an isolated bacterium to a particular drug. This study determined the zone of inhibition, minimum inhibitory concentration (MIC) and time at which bacteria showed resistance. From sensitivity test, it showed that P. aeruginosa is sensitive to azithromycin antibiotic. MIC level of P. aeruginosa that was found from the analysis was 3 μg/ml and from further analysis it was found that P. aeruginosa grew resistance when it got up to 2.5 μg/ml concentration of antibiotic below MIC level for 24 hours. When the P. aeruginosa was treated with the concentration upto 2.5 μg/ml for 24 hours then it showed growth at the concentration of MIC level. It means that P. aeruginosa got the drug below MIC level for a certain period and became resistant to azithromycin.Bangladesh Pharmaceutical Journal 21(1): 42-46, 2018

Download Full-text