scholarly journals All d-Lysine Analogues of the Antimicrobial Peptide HPA3NT3-A2 Increased Serum Stability and without Drug Resistance

2020 ◽  
Vol 21 (16) ◽  
pp. 5632
Author(s):  
Jong-Kook Lee ◽  
Yoonkyung Park

Novel antibiotic drugs are urgently needed because of the increase in drug-resistant bacteria. The use of antimicrobial peptides has been suggested to replace antibiotics as they have strong antimicrobial activity and can be extracted from living organisms such as insects, marine organisms, and mammals. HPA3NT3-A2 ([Ala1,8] HPA3NT3) is an antimicrobial peptide that is an analogue of the HP (2–20) peptide derived from Helicobacter pylori ribosomal protein L1. Although this peptide was shown to have strong antimicrobial activity against drug-resistant bacteria, it also showed lower toxicity against sheep red blood cells (RBCs) and HaCaT cells compared to HPA3NT3. The l-Lys residues of HPA3NT3-A2 was substituted with d-Lys residues (HPA3NT3-A2D; [d-Lys2,5,6,9,10,15] HPA3NT3-A2) to prevent the cleavage of peptide bonds by proteolytic enzymes under physiological conditions. This peptide showed an increased half-life and maintained its antimicrobial activity in the serum against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (pathogen). Furthermore, the antimicrobial activity of HPA3NT3-A2D was not significantly affected in the presence of mono- or divalent ions (Na+, Mg2+, Ca2+). Finally, l- or d-HPA3NT3-A2 peptides exhibited the strongest antimicrobial activity against antibiotic-resistant bacteria and failed to induce resistance in Staphylococcus aureus after 12 passages.

2019 ◽  
Vol 7 (12) ◽  
pp. 5068-5083 ◽  
Author(s):  
Jong-Kook Lee ◽  
Loredana Mereuta ◽  
Tudor Luchian ◽  
Yoonkyung Park

Bacterial biofilms formed through secretion of extracellular polymeric substances (EPS) have been implicated in many serious infections and can increase antibiotic resistance by a factor of more than 1000.


2015 ◽  
Vol 31 (2) ◽  
pp. 137-142 ◽  
Author(s):  
N. Benmansour ◽  
A. Benmansour ◽  
F. El Hanbali ◽  
M. C. González-Mas ◽  
M. A. Blázquez ◽  
...  

2020 ◽  
Author(s):  
◽  
David Serunjogi ◽  
Kizito Muwonge

Background: Plant species such as the guava have been used in Uganda and elsewhere in the world to treat some of the medical conditions associated with bacteria, this is due to the increased number of drug resistant bacteria in the world. In this study, the antimicrobial activity of guava leaf extracts against some of the disease causing bacteria isolated from Kisubi hospital in Uganda is discussed. Methods: The guava leafs were collected from a plantation near Zika forest in Uganda (0°7′27″N 32°31′32″E / 0.12417°N 32.52556°E / 0.12417; 32.52556) and samples were put in a bag and transferred to the university laboratory where they were identified. The extracts were obtained by maceration using distilled water, 30%, 50% and 70 % methanol as the extraction solvents. Antimicrobial susceptibility testing was conducted using the disc diffusion method. Results: Gram-negative Escherichia coli was sensitive to the plant extract and synthetic commercial drugs such as trimethoprim-sulfamethozole, ciprofloxacin, and Gentamicin. Pseudomonas aeruginosa was resistant to all drugs. Streptococcus pneumonia and Staphylococcus aureus were all sensitive to the plant extracts with measurable inhibition zones. Conclusion: The Guava tree leaf crude extracts have antimicrobial activity against drug-resistant bacteria. More studies should be carried out to know the potency and the concentration of different plant origin extracts.


2015 ◽  
Vol 59 (5) ◽  
pp. 2835-2841 ◽  
Author(s):  
Qinghua Zhang ◽  
Yanzhao Xu ◽  
Qing Wang ◽  
Bolin Hang ◽  
Yawei Sun ◽  
...  

ABSTRACTWith the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activityin vitro. We evaluated the antimicrobial activities of P3 and an analog, JH-3, bothin vitroandin vivo. The MICs of P3 and JH-3 ranged from 3.125 μg/ml to 50 μg/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an α-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD50) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activities and relatively low toxicities in a mouse model, indicating that they may be useful for treating infections caused by drug-resistant bacteria.


MedChemComm ◽  
2018 ◽  
Vol 9 (6) ◽  
pp. 1017-1032
Author(s):  
Davide Carta ◽  
Paola Brun ◽  
Matteo Dal Pra ◽  
Giulia Bernabè ◽  
Ignazio Castagliuolo ◽  
...  

The new diflunisal aza-analogs multi-target approach is remarkable in the treatment of infections induced by multi-drug resistant bacteria. Diflunisal aza-analogs preserved the anti-inflammatory activity and significantly potentiated the antimicrobial activity of antibiotics.


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