Nonspecific porins of the outer membrane of Gram-negative bacteria: Structure and functions

Novikova, O. D.; Solovyeva, T. F.

doi:10.1134/s1990747809010024

Cited by 13 publications

(10 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The highest MIC value was for P. aeruginosa with an MIC and MBC values of 5000 and 40000 µg/mL, respectively. As was explained earlier, vancomycin cannot penetrate the outer membrane of Gram-negative bacteria, due to its high molecular weight of about 1400 D and hydrophilicity (11,42,43). Gram-positive bacteria however, lack this outer membrane layer and therefore, as is confirmed by our results, vancomycin is effective against these bacteria while, it cannot show enough antibacterial effect on Gram-negative ones.…”

Section: Discussionsupporting

confidence: 79%

PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria

et al. 2018

View full text Add to dashboard Cite

Purpose: The antibacterial activity of some antibiotics is specific to either Gram-positive or Gram-negative bacteria. There are different mechanisms behind such insensitivities like inability of antibiotics to permeate through some bacterial membranes, as is the case for vancomycin in Gram-negative bacteria. The present investigation tries to overcome this problem by dendrimers, in order to make Gram-negative bacteria responsive to vancomycin. Methods: The effects of generations 3 (G3) and 5 (G5) polyamidoamine amine-terminated dendrimers (NH2-PAMAM), on the antibacterial activity of vancomycin, were evaluated. Vancomycin-PAMAM dendrimers complexes were prepared and their antibacterial activities were evaluated by determination of their “minimum inhibitory concentration (MIC)”, “minimum bactericidal concentration” and “fractional inhibitory concentration index” values against two Gram-positive and four Gram-negative bacteria, using broth micro-dilution method. The complexation of vancomycin and dendrimers was also assessed by in vitro release studies across dialysis tubing using a developed HPLC method. Results: Results showed that vancomycin solution was effective against Gram-positive bacteria, but, was not effective in Gram-negative ones. Vancomycin-PAMAM dendrimers exhibited significant antibacterial efficacy against Gram-negative bacteria resulting in a decline of vancomycin MIC values by about 2, 2, 4 and 64 times in E. coli, K. pneumonia, S. typhimurium and P. aeruginosa, respectively. Results also showed that enhanced effect by G5 is more than G3. Dendrimers did not affect antibacterial activity of vancomycin in Gram-positive bacteria, as no permeation problem exists here. Conclusions: The present study revealed that both G3 and G5 cationic PAMAM dendrimers are able to make Gram-negative bacteria sensitive to vancomycin, resulting in decline of MIC values up to 64 times, possibly by increasing its permeation through bacterial membrane. These results look promising for broadening the antibacterial spectrum of vancomycin and such a strategy might be used for increasing the overall life of antibiotics.

show abstract

Section: Discussionsupporting

confidence: 79%

PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Porins are proteins found in the membranes of Gram-negative bacteria, intended for passive diffusion of hydrophilic molecules with the molecular weight of no more than 600 Da. 40,41 They form transmembrane water-filled channels (or pores) that provide the exchange of low-molecular substances between cell and environment. ParELC3 is too large to fit and pass by these channels.…”

Section: Resultsmentioning

confidence: 99%

“…ParELC3 is too large to fit and pass by these channels. 41 . Thus, ParELC3 and its fluorescent derivatives were encapsulated in RL liposomes prepared by sonication to generate the respective nanosized unilamellar vesicles.…”

Section: Resultsmentioning

confidence: 99%

Rhamnolipid-Based Liposomes as Promising Nano-Carriers for Enhancing the Antibacterial Activity of Peptides Derived from Bacterial Toxin-Antitoxin Systems

Sanches¹,

Rocha²,

Bedoya³

et al. 2021

IJN

View full text Add to dashboard Cite

Background: Antimicrobial resistance poses substantial risks to human health. Thus, there is an urgent need for novel antimicrobial agents, including alternative compounds, such as peptides derived from bacterial toxin-antitoxin (TA) systems. ParELC3 is a synthetic peptide derived from the ParE toxin reported to be a good inhibitor of bacterial topoisomerases and is therefore a potential antibacterial agent. However, ParELC3 is inactive against bacteria due to its inability to cross the bacterial membranes. To circumvent this limitation we prepared and used rhamnolipid-based liposomes to carry and facilitate the passage of ParELC3 through the bacterial membrane to reach its intracellular target-the topoisomerases. Methods and Results: Small unilamellar liposome vesicles were prepared by sonication from three formulations that included 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and cholesterol. ParELC3 was loaded with high efficiency into the liposomes. Characterization by DLS and TEM revealed the appropriate size, zeta potential, polydispersity index, and morphology. In vitro microbiological experiments showed that ParELC3 loaded-liposomes are more efficient (29 to 11 µmol•L −1) compared to the free peptide (>100 µmol•L −1) at inhibiting the growth of standard E. coli and S. aureus strains. RL liposomes showed high hemolytic activity but when prepared with POPC and Chol this activity had a significant reduction. Independently of the formulation, the vesicles had no detectable cytotoxicity to HepG2 cells, even at the highest concentrations tested (1.3 mmol•L −1 and 50 µmol•L −1 for rhamnolipid and ParELC3, respectively). Conclusion: The present findings suggest the potential use of rhamnolipid-based liposomes as nanocarrier systems to enhance the bioactivity of peptides.

show abstract

“…Besides, these seven sequences showed varying degrees of antibacterial activities against tested bacteria, which indicated hydrophilic amino acids a vital role in adjusting the antibacterial spectrum. First, S1 and S2, which had higher value of H (H represented the total hydrophobicity (sum of all residue hydrophobicity indices) divided by number of residues), showed lower antimicrobial activity against the Gram-negative E. coli demonstrated that the hydrophobicity of cysteine (C) or tyrosine (Y) was too high for this sequence, which might prevent these two peptides from transporting through nonspecific transmembrane water-filled channels (or pores) of outer membrane of Gram-negative (Novikova and Solovyeva, 2009). Additionally, the non-activity of S3 indicated that the hydrophilicity of S3 might be not enough to break down the bacterial membrane because the high hydrophilicity of asparagine (N) decreased the total hydrophobicity of S3.…”

Section: Discussionmentioning

confidence: 99%

Peptides With Triplet-Tryptophan-Pivot Promoted Pathogenic Bacteria Membrane Defects

Chou

Зайцева

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

Development of probiotic-ineffective antimicrobial peptides (AMPs)-based coatings that can kill pathogenic bacteria at low concentrations but are essentially harmless (even high concentrations) to probiotic organisms is a relatively new trend for therapy against GI tract infections. In this study, a series of triplet-tryptophan-pivot peptides with various hydrophilic amino acids was constructed. One AMP in particular, S7, showed bactericidal activity against Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli and antibiotic-resistant Staphylococcus aureus, yet was shown to be harmless to Lactobacillus rhamnosus, a key GI tract commensal. Furthermore, antibacterial mechanism assays, drug resistance assays, and mouse model tests suggested that S7 was useful in a clinical setting as it proved to significantly reduce bacterial load and cytokines (TNF-α, IL-6; P < 0.05) with a low probability of resistance via bacterial membrane physical destruction and formation of intracellular ROS. Combined, the results show that a triplet-tryptophan-pivot peptide containing a pair of serine residues was an excellent pathogen-selective candidate for medical devices and was potentially useful in food preservation, crop protection, and human health.

show abstract

Nonspecific porins of the outer membrane of Gram-negative bacteria: Structure and functions

Cited by 13 publications

References 69 publications

PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria

PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria

Rhamnolipid-Based Liposomes as Promising Nano-Carriers for Enhancing the Antibacterial Activity of Peptides Derived from Bacterial Toxin-Antitoxin Systems

Peptides With Triplet-Tryptophan-Pivot Promoted Pathogenic Bacteria Membrane Defects

Contact Info

Product

Resources

About