scholarly journals The antibiotic negamycin crosses the bacterial cytoplasmic membrane by multiple routes

2021 ◽  
Author(s):  
Daniel Hörömpöli ◽  
Catherine Ciglia ◽  
Karl-Heinz Glüsenkamp ◽  
Lars Ole Haustedt ◽  
Hildegard Falkenstein-Paul ◽  
...  
Keyword(s):  
Cytoplasmic Membrane ◽  
Binding Mode ◽  
Blood Levels ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Target Interaction ◽  
Gram Positive Bacteria ◽  
Multiple Routes ◽  
Resistance Rates

Negamycin is a natural pseudo-dipeptide antibiotic with promising activity against Gram-negative and Gram-positive bacteria, including Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus, and good efficacy in infection models. It binds to ribosomes with a novel binding mode, stimulating miscoding and inhibiting ribosome translocation. We were particularly interested in studying how the small, positively charged natural product reaches its cytoplasmic target in Escherichia coli. Negamycin crosses the cytoplasmic membrane by multiple routes depending on environmental conditions. In a peptide-free medium, negamycin uses endogenous peptide transporters for active translocation, preferentially the dipeptide permease Dpp. However, in the absence of functional Dpp or in the presence of outcompeting nutrient peptides, negamycin can still enter the cytoplasm. We observed a contribution of the DppA homologs SapA and OppA, as well as of DtpD, a proton-dependent oligopeptide transporter. Calcium strongly improves the activity of negamycin against both Gram-negative and Gram-positive bacteria, especially at concentrations around 2.5 mM, reflecting human blood levels. Calcium forms a complex with negamycin and facilitates its interaction with negatively charged phospholipids in bacterial membranes. Moreover, decreased activity at acidic pH and under anaerobic conditions point to a role of the membrane potential in negamycin uptake. Accordingly, improved activity at alkaline pH could be linked to increased uptake of [3H]negamycin. The diversity of options for membrane translocation is reflected by low resistance rates. The example of negamycin demonstrates that membrane passage of antibiotics can be multi-faceted and that for cytoplasmic anti-Gram-negative drugs, understanding of permeation and target interaction are equally important.

scholarly journals Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum

2021 ◽  
Author(s):  
Erum Malik ◽  
David A. Phoenix ◽  
Timothy J. Snape ◽  
Frederick Harris ◽  
Jaipaul Singh ◽  
...  
Keyword(s):  
Helical Structure ◽  
Food Preservation ◽  
Forming Process ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria ◽  
Alkaline Conditions ◽  
Ph Dependent ◽  
Gram Negative Organisms

AbstractHere the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5–26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3–5.1 mN m−1) and lyse (↑ 15.1–32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1–23) in the N → C direction, with −  < µH > increasing overall from circa − 0.8 to − 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.

scholarly journals Effects of Antibacterial Peptide F1 on Bacterial Liposome Membrane Integrity

2021 ◽  
Vol 8 ◽  
Author(s):  
Qun Wang ◽  
Bo Peng ◽  
Mingyue Song ◽  
Abdullah ◽  
Jun Li ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Membrane Structure ◽  
Bacterial Membrane ◽  
Phospholipid Membranes ◽  
Phospholipid Membrane ◽  
Gram Positive ◽  
Liposome Membrane ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria

Previous studies from our lab have shown that the antimicrobial peptide F1 obtained from the milk fermentation by Lactobacillus paracasei FX-6 derived from Tibetan kefir was different from common antimicrobial peptides; specifically, F1 simultaneously inhibited the growth of Gram-negative and Gram-positive bacteria. Here, we present follow-on work demonstrating that after the antimicrobial peptide F1 acts on either Escherichia coli ATCC 25922 (E. coli) or Staphylococcus aureus ATCC 63589 (S. aureus), their respective bacterial membranes were severely deformed. This deformation allowed leakage of potassium and magnesium ions from the bacterial membrane. The interaction between the antimicrobial peptide F1 and the bacterial membrane was further explored by artificially simulating the bacterial phospholipid membranes and then extracting them. The study results indicated that after the antimicrobial peptide F1 interacted with the bacterial membranes caused significant calcein leakage that had been simulated by different liposomes. Furthermore, transmission electron microscopy observations revealed that the phospholipid membrane structure was destroyed and the liposomes presented aggregation and precipitation. Quartz Crystal Microbalance with Dissipation (QCM-D) results showed that the antimicrobial peptide F1 significantly reduced the quality of liposome membrane and increased their viscoelasticity. Based on the study's findings, the phospholipid membrane particle size was significantly increased, indicating that the antimicrobial peptide F1 had a direct effect on the phospholipid membrane. Conclusively, the antimicrobial peptide F1 destroyed the membrane structure of both Gram-negative and Gram-positive bacteria by destroying the shared components of their respective phospholipid membranes which resulted in leakage of cell contents and subsequently cell death.

Distinct antibacterial activity of a vertically aligned graphene coating against Gram-positive and Gram-negative bacteria

2020 ◽  
Vol 8 (28) ◽  
pp. 6069-6079
Author(s):  
Wei Wei ◽  
Jiurong Li ◽  
Zeyang Liu ◽  
Yuan Deng ◽  
Da Chen ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Gram Negative Bacteria ◽  
Antibacterial Mechanism ◽  
Si Substrate ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria ◽  
Graphene Coating ◽  
Vertically Aligned

The distinct antibacterial mechanism of vertical graphene Si toward bacteria. Vertical graphene kills Gram-positive bacteria through physical disruption and Si substrate kills Gram-negative bacteria by extracting electrons from bacterial membranes.

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

2018 ◽  
Vol 22 ◽  
pp. 10-21 ◽  
Author(s):  
Azadeh Serri ◽  
Arash Mahboubi ◽  
Afshin Zarghi ◽  
Hamid Reza Moghimi
Keyword(s):  
Antibacterial Activity ◽  
Inhibitory Concentration ◽  
In Vitro Release ◽  
Pamam Dendrimers ◽  
Dilution Method ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria

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.

scholarly journals Prevalence of Gram-negative and Gram-positive Bacteria and Antibiotic Resistance Rates at a Military Hospital in Riyadh Region

2021 ◽  
Vol 13 (4) ◽  
pp. 392-395
Author(s):  
Nehad Jaser Ahmed ◽  
Mohammad Abdalla ◽  
Hadeel Alahmadi ◽  
Abdul Haseeb ◽  
Amer Hayat Khan
Keyword(s):  
Antibiotic Resistance ◽  
Military Hospital ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Resistance Rates

CONTRIBUTION ON THE BEHAVIOR AND STRUCTURE OF THE CYTOPLASMIC MEMBRANE OF BACTERIA

1952 ◽  
Vol 30 (1) ◽  
pp. 86-105
Author(s):  
Roland Fischer ◽  
P. Larose
Keyword(s):  
Cytoplasmic Membrane ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Gram Staining ◽  
Composition And Structure ◽  
The One ◽  
Future Work ◽  
Positive State

The relations previously found to exist between the bactericidal activity of substances and their affinity for wool have been used as the basis for a further study of the similarity between Gram-negative bacteria and intact wool on the one hand, and between Gram-positive bacteria and degraded wool on the other. A porrespondence in behavior has been shown to exist in the case of Gram-staining, of the Eisenberg–Gutstein techniques, and of the Feulgen reaction. It was possible to produce with degraded wool a conversion from a Gram-positive state to a Gram-negative one (corresponding to that of intact wool) just as it is possible to carry out the similar conversion with Gram-positive bacteria by using oxidizing and/or acidic agents. Reconversion to the original Gram-positive state was also shown to be possible with reducing and/or alkaline agents. A mechanism is offered to explain the above findings and the respective cytochemical reactions characteristic of the cytoplasmic membrane of the bacteria. This mechanism is based on similarities in composition and structure (α-keratin) between the cytoplasmic membrane of Gram-positive bacteria and degraded wool, and the “cytoplasmic membrane” of Gram-negative bacteria and intact wool. Further possible similarities are pointed out. A new definition for bactericidal action is given in the light of these results. A direction for future work is indicated and discussed.

Ultrastructure of the cell wall and the mechanism of cellular division of a Gram-variable coccus

1971 ◽  
Vol 17 (3) ◽  
pp. 421-424 ◽  
Author(s):  
H. E. Gilleland Jr. ◽  
I. L. Roth ◽  
R. G. Eagon
Keyword(s):  
Cell Wall ◽  
Outer Membrane ◽  
Ultrastructural Study ◽  
Cytoplasmic Membrane ◽  
Gram Positive ◽  
Cellular Division ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Isolated Cell ◽  
Peptidoglycan Layer

An ultrastructural study of a Gram-variable coccus was carried out. The cell wall of this microorganism was composed of an inner peptidoglycan layer, a middle electron-transparent compartment, and an undulating trilayered outer membrane. This microorganism also possessed numerous mesosomes which were simple bulb-like invaginations of the cytoplasmic membrane. The mechanism of cellular division involved the formation of a septum by the cytoplasmic membrane and the inner layer of the cell wall. Membranous structures were associated with the developing septum throughout the process. The outer membrane of the cell wall did not invaginate with the inner layer but reformed as the completed septum began to split. In isolated cell wall preparations, no 2-keto-3-deoxyoctonate or heptose could be detected. It is suggested that the Gram-variable cocci previously classified as micrococci may represent a group that is intermediate between true Gram-negative and Gram-positive bacteria.

scholarly journals Analysis of pathogenic distribution and drug resistance of catheter-related blood stream infection in hemodialysis patients with vein tunneled cuffed catheter

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Wei Ren ◽  
Jun Jiang ◽  
Yan Wang ◽  
Yan Jin ◽  
Yuan Fang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Culture ◽  
Blood Stream ◽  
Resistance Rate ◽  
Penicillin G ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Positive Rate ◽  
Resistance Rates

The catheter related blood stream infections (CRBSI) in hemodialysis (HD) patients with vein tunneled cuffed catheter (TCC) and misuse of antibiotic in clinical practice seriously affected the prognosis of MHD patients. The present study aimed to investigate the pathogen distribution and drug resistance of CRBSI in HD patients with TCC to guide clinical empirical pharmacy. The clinical data of 75 HD patients with TCC diagnosed with CRBSI between January 2011 and March 2015 were retrospectively collected, and the distribution and drug resistance of pathogens were analyzed. In 75 HD patients with TCC diagnosed with CRBSI, there were 33 patients with positive blood culture, and the positive rate of blood culture was 44%. The majority of the 33 pathogens were Gram-positive bacteria (22 strains, accounting for 66.7%). Gram-positive cocci hardly resisted to vancomycin and linezolid, while the resistance rate to penicillin G nearly reached to 100%. Gram-negative bacilli had low resistance rates to carbapenems and quinolone antibiotics, and the resistance rate to cephalosporins antibioticsexceeding 50%. The positive rate of blood culture in 75 HD patients with TCC diagnosed with CRBSI is low. The pathogens resulting in CRBSI in HD patients are mainly Gram-positive bacteria which are significantly resistant to penicillin G, and have a low resistance rate to methicillin. Gram-negative bacteria have high resistance rates to commonly used antibiotics. The pathogen examination should be performed as early as possible and effective antibiotics should be chosen according to drug sensitivity test results in CRBSI in HD patients.

Microanatomy of the Periplasm of Bacillus Licheniformis

1971 ◽  
Vol 29 ◽  
pp. 262-263
Author(s):  
B.K. Ghosh
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Bacillus Licheniformis ◽  
External Environment ◽  
Permeability Barrier ◽  
Periplasmic Space ◽  
Modified Technique ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Periplasm of bacteria is the space outside the permeability barrier of plasma membrane but enclosed by the cell wall. The contents of this special milieu exterior could be regulated by the plasma membrane from the internal, and by the cell wall from the external environment of the cell. Unlike the gram-negative organism, the presence of this space in gram-positive bacteria is still controversial because it cannot be clearly demonstrated. We have shown the importance of some periplasmic bodies in the secretion of penicillinase from Bacillus licheniformis.In negatively stained specimens prepared by a modified technique (Figs. 1 and 2), periplasmic space (PS) contained two kinds of structures: (i) fibrils (F, 100 Å) running perpendicular to the cell wall from the protoplast and (ii) an array of vesicles of various sizes (V), which seem to have evaginated from the protoplast.

Rapid demonstration of septic or infectious arthritis due to Gram-negative bacteria

1992 ◽  
Vol 50 (1) ◽  
pp. 686-687
Author(s):  
Jacob S. Hanker ◽  
Paul R. Gross ◽  
Beverly L. Giammara
Keyword(s):  
Chronic Arthritis ◽  
Blood Cultures ◽  
Gram Negative Bacteria ◽  
Infectious Arthritis ◽  
Bacterial Arthritis ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Blood cultures are positive in approximately only 50 per cent of the patients with nongonococcal bacterial infectious arthritis and about 20 per cent of those with gonococcal arthritis. But the concept that gram-negative bacteria could be involved even in chronic arthritis is well-supported. Gram stains are more definitive in staphylococcal arthritis caused by gram-positive bacteria than in bacterial arthritis due to gram-negative bacteria. In the latter situation where gram-negative bacilli are the problem, Gram stains are helpful for 50% of the patients; they are only helpful for 25% of the patients, however, where gram-negative gonococci are the problem. In arthritis due to gram-positive Staphylococci. Gramstained smears are positive for 75% of the patients.

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