Potent bactericidal activity of reduced cryptdin-4 derived from its hydrophobicity and mediated by bacterial membrane disruption

Amino Acids ◽  
2022 ◽  
Author(s):  
Yuji Sato ◽  
Yi Wang ◽  
Yuchi Song ◽  
Weiming Geng ◽  
Shaonan Yan ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Membrane Disruption ◽  
Bacterial Membrane

scholarly journals Alarmone Ap4A is elevated by aminoglycoside antibiotics and enhances their bactericidal activity

2019 ◽  
Vol 116 (19) ◽  
pp. 9578-9585 ◽  
Author(s):  
Xia Ji ◽  
Jin Zou ◽  
Haibo Peng ◽  
Anne-Sophie Stolle ◽  
Ruiqiang Xie ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Trna Synthetase ◽  
Aminoglycoside Antibiotics ◽  
Membrane Disruption ◽  
Bacterial Membrane ◽  
Bacterial Killing ◽  
Messenger Molecules ◽  
Increased Susceptibility

Second messenger molecules play important roles in the responses to various stimuli that can determine a cell's fate under stress conditions. Here, we report that lethal concentrations of aminoglycoside antibiotics result in the production of a dinucleotide alarmone metabolite–diadenosine tetraphosphate (Ap4A), which promotes bacterial cell killing by this class of antibiotics. We show that the treatment ofEscherichia coliwith lethal concentrations of kanamycin (Kan) dramatically increases the production of Ap4A. This elevation of Ap4A is dependent on the production of a hydroxyl radical and involves the induction of the Ap4A synthetase lysyl-tRNA synthetase (LysU). Ectopic alteration of intracellular Ap4A concentration via the elimination of the Ap4A phosphatase diadenosine tetraphosphatase (ApaH) and the overexpression of LysU causes over a 5,000-fold increase in bacterial killing by aminoglycosides. This increased susceptibility to aminoglycosides correlates with bacterial membrane disruption. Our findings provide a role for the alarmone Ap4A and suggest that blocking Ap4A degradation or increasing its synthesis might constitute an approach to enhance aminoglycoside killing potency by broadening their therapeutic index and thereby allowing lower nontoxic dosages of these antibiotics to be used in the treatment of multidrug-resistant infections.

Synthesis of antimicrobial cyclodextrins bearing polyarylamino and polyalkylamino groups via click chemistry for bacterial membrane disruption

2014 ◽  
Vol 50 (41) ◽  
pp. 5444 ◽  
Author(s):  
Hatsuo Yamamura ◽  
Yuuki Sugiyama ◽  
Kensuke Murata ◽  
Takanori Yokoi ◽  
Ryuji Kurata ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Membrane Disruption ◽  
Bacterial Membrane

scholarly journals Construction of Antibacterial N ‐Halamine Polymer Nanomaterials Capable of Bacterial Membrane Disruption for Efficient Anti‐Infective Wound Therapy

2019 ◽  
Vol 19 (4) ◽  
pp. 1970010 ◽  
Author(s):  
Yangyang Gao ◽  
Nan Song ◽  
Wenxin Liu ◽  
Alideertu Dong ◽  
Yan‐Jie Wang ◽  
...  
Keyword(s):  
Membrane Disruption ◽  
Bacterial Membrane ◽  
Wound Therapy

Construction of Antibacterial N ‐Halamine Polymer Nanomaterials Capable of Bacterial Membrane Disruption for Efficient Anti‐Infective Wound Therapy

2019 ◽  
Vol 19 (4) ◽  
pp. 1800453 ◽  
Author(s):  
Yangyang Gao ◽  
Nan Song ◽  
Wenxin Liu ◽  
Alideertu Dong ◽  
Yan‐Jie Wang ◽  
...  
Keyword(s):  
Membrane Disruption ◽  
Bacterial Membrane ◽  
Wound Therapy

scholarly journals Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption

2021 ◽  
Author(s):  
Chenlu Zhang ◽  
Zehan Hu ◽  
Abdul G Lone ◽  
Methinee Artami ◽  
Marshall Edwards ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bactericidal Activity ◽  
Skin Infection ◽  
Mouse Skin ◽  
Systemic Infection ◽  
Bacterial Membrane ◽  
Antimicrobial Proteins ◽  
Antimicrobial Function ◽  
Skin Commensals ◽  
Insight Into

Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Further, LPS injected into mouse skin triggered the expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through stimulation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa and skin commensals. Thus, Sprr1a-/-;Sprr2a-/- mice are more susceptible to MRSA and Pseudomonas aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.

scholarly journals Biomimetic Electronic Devices for Measuring Bacterial Membrane Disruption

2018 ◽  
Vol 30 (39) ◽  
pp. 1803130 ◽  
Author(s):  
Charalampos Pitsalidis ◽  
Anna-Maria Pappa ◽  
Mintu Porel ◽  
Christine M. Artim ◽  
Gregorio C. Faria ◽  
...  
Keyword(s):  
Electronic Devices ◽  
Membrane Disruption ◽  
Bacterial Membrane
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