scholarly journals The structure of the antimicrobial human cathelicidin LL-37 shows oligomerization and channel formation in the presence of membrane mimics

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Enea Sancho-Vaello ◽  
David Gil-Carton ◽  
Patrice François ◽  
Eve-Julie Bonetti ◽  
Mohamed Kreir ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
Bacterial Cell ◽  
Lipid Membranes ◽  
Bacterial Infections ◽  
Rational Design ◽  
Critical Role ◽  
Time Lapse ◽  
Dynamic Simulations ◽  
Bacterial Cell Death

Abstract The human cathelicidin LL-37 serves a critical role in the innate immune system defending bacterial infections. LL-37 can interact with molecules of the cell wall and perforate cytoplasmic membranes resulting in bacterial cell death. To test the interactions of LL-37 and bacterial cell wall components we crystallized LL-37 in the presence of detergents and obtained the structure of a narrow tetrameric channel with a strongly charged core. The formation of a tetramer was further studied by cross-linking in the presence of detergents and lipids. Using planar lipid membranes a small but defined conductivity of this channel could be demonstrated. Molecular dynamic simulations underline the stability of this channel in membranes and demonstrate pathways for the passage of water molecules. Time lapse studies of E. coli cells treated with LL-37 show membrane discontinuities in the outer membrane followed by cell wall damage and cell death. Collectively, our results open a venue to the understanding of a novel AMP killing mechanism and allows the rational design of LL-37 derivatives with enhanced bactericidal activity.

scholarly journals N-Acetyl-cysteine and Mechanisms Involved in Resolution of Chronic Wound Biofilm

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Xin Li ◽  
Jane Kim ◽  
Jiabin Wu ◽  
Alaa’ I Ahamed ◽  
Yinsheng Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Diabetic Mouse ◽  
Bacterial Survival ◽  
Bacterial Cell Death ◽  
Carboxylic Groups ◽  
Acetyl Cysteine

Chronic wounds are a major global health problem with the presence of biofilm significantly contributing to wound chronicity. Current treatments are ineffective in resolving biofilm and simultaneously killing the bacteria; therefore, effective biofilm-resolving drugs are needed. We have previously shown that, together with α-tocopherol, N-acetyl-cysteine (NAC) significantly improves the healing of biofilm-containing chronic wounds, in a diabetic mouse model we developed, by causing disappearance of the bacteria and breakdown of the extracellular polymeric substance (EPS). We hypothesize that NAC creates a microenvironment that affects bacterial survival and EPS integrity. To test this hypothesis, we developed an in vitro biofilm system using microbiome taken directly from diabetic mouse chronic wounds. For these studies, we chose mice in which chronic wound microbiome was rich in Pseudomonas aeruginosa (97%). We show that NAC at concentrations with pH < pKa causes bacterial cell death and breakdown of EPS. When used before biofilm is formed, NAC leads to bacterial cell death whereas treatment after the biofilm is established NAC causes biofilm dismantling accompanied by bacterial cell death. Mechanistically, we show that NAC can penetrate the bacterial membrane, increase oxidative stress, and halt protein synthesis. We also show that low pH is important for the actions of NAC and that bacterial death occurs independently of the presence of biofilm. In addition, we show that both the acetyl and carboxylic groups play key roles in NAC functions. The results presented here provide insight into the mechanisms by which NAC dismantles biofilm and how it could be used to treat chronic wounds after debridement (NAC applied at the start of culture) or without debridement (NAC applied when biofilm is already formed). This approach can be taken to develop biofilm from microbiome taken directly from human chronic wounds to test molecules that could be effective for the treatment of specific biofilm compositions.

scholarly journals Novel Quorum-Sensing Peptides Mediating Interspecies Bacterial Cell Death

mBio ◽  
2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Sathish Kumar ◽  
Ilana Kolodkin-Gal ◽  
Hanna Engelberg-Kulka
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Death ◽  
Bacillus Subtilis ◽  
Quorum Sensing ◽  
Bacterial Cell ◽  
Content Type ◽  
E Coli ◽  
New Class ◽  
Bacterial Cell Death ◽  
Induced Module

ABSTRACTEscherichia colimazEFis a toxin-antitoxin stress-induced module mediating cell death. It requires the quorum-sensing signal (QS) “extracellular death factor” (EDF), the penta-peptide NNWNN (EcEDF), enhancing the endoribonucleolytic activity ofE. colitoxin MazF. Here we discovered thatE. coli mazEF-mediated cell death could be triggered by QS peptides from the supernatants (SN) of the Gram-positive bacteriumBacillus subtilisand the Gram-negative bacteriumPseudomonas aeruginosa. In the SN ofB. subtilis, we found one EDF, the hexapeptide RGQQNE, calledBsEDF. In the SN ofP. aeruginosa, we found three EDFs: the nonapeptide INEQTVVTK, calledPaEDF-1, and two hexadecapeptides, VEVSDDGSGGNTSLSQ, calledPaEDF-2, and APKLSDGAAAGYVTKA, calledPaEDF-3. When added to a dilutedE. colicultures, each of these peptides acted as an interspecies EDF that triggeredmazEF-mediated death. Furthermore, though their sequences are very different, each of these EDFs amplified the endoribonucleolytic activity ofE. coliMazF, probably by interacting with different sites onE. coliMazF. Finally, we suggest that EDFs may become the basis for a new class of antibiotics that trigger death from outside the bacterial cells.IMPORTANCEBacteria communicate with one another via quorum-sensing signal (QS) molecules. QS provides a mechanism for bacteria to monitor each other’s presence and to modulate gene expression in response to population density. Previously, we addedE. coliEDF (EcEDF), the peptide NNWNN, to this list of QS molecules. Here we extended the group of QS peptides to several additional different peptides. The new EDFs are produced by two other bacteria,Bacillus subtilisandPseudomonas aeruginosa. Thus, in this study we established a “new family of EDFs.” This family provides the first example of quorum-sensing molecules participating in interspecies bacterial cell death. Furthermore, each of these peptides provides the basis of a new class of antibiotics triggering death by acting from outside the cell.

The extract of Hypericum ascyron L. induces bacterial cell death through apoptosis pathway

2015 ◽  
Vol 166 ◽  
pp. 205-210 ◽  
Author(s):  
Xiu-Mei Li ◽  
Xue-Gang Luo ◽  
Nan Wang ◽  
Hao Zhou ◽  
Chuan-Ling Si ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Apoptosis Pathway ◽  
Bacterial Cell Death

Hydroxychavicol, a key ingredient of Piper betle induces bacterial cell death by DNA damage and inhibition of cell division

2018 ◽  
Vol 120 ◽  
pp. 62-71 ◽  
Author(s):  
Deepti Singh ◽  
Shwetha Narayanamoorthy ◽  
Sunita Gamre ◽  
Ananda Guha Majumdar ◽  
Manish Goswami ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cell Division ◽  
Bacterial Cell ◽  
Piper Betle ◽  
Bacterial Cell Death

scholarly journals Death effector domain of a mammalian apoptosis mediator, FADD, induces bacterial cell death

2002 ◽  
Vol 35 (6) ◽  
pp. 1540-1549 ◽  
Author(s):  
Sang Won Lee ◽  
Young--gyu Ko ◽  
SookHee Bang ◽  
Key-Sun Kim ◽  
Sunghoon Kim
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Effector Domain ◽  
Death Effector Domain ◽  
Bacterial Cell Death ◽  
Death Effector

scholarly journals Antibiotic-Induced Bacterial Cell Death Exhibits Physiological and Biochemical Hallmarks of Apoptosis

2012 ◽  
Vol 46 (5) ◽  
pp. 561-572 ◽  
Author(s):  
Daniel J. Dwyer ◽  
Diogo M. Camacho ◽  
Michael A. Kohanski ◽  
Jarred M. Callura ◽  
James J. Collins
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Bacterial Cell Death ◽  
Physiological And Biochemical

scholarly journals Recombinant Cyclophilins Lack Nuclease Activity

2004 ◽  
Vol 186 (18) ◽  
pp. 6325-6326 ◽  
Author(s):  
Angel Manteca ◽  
Jesus Sanchez
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Bacterial Cell ◽  
Intrinsic Property ◽  
Nuclease Activity ◽  
Dna Degradation ◽  
Single Domain ◽  
Bacterial Cell Death

ABSTRACT Several single-domain prokaryotic and eukaryotic cyclophilins have been identified as also being unspecific nucleases with a role in DNA degradation during the lytic processes that accompany bacterial cell death and eukaryotic apoptosis. Evidence is provided here that the supposed nuclease activity of human and bacterial recombinant cyclophilins is due to contamination of the proteins by the host Escherichia coli endonuclease and is not an intrinsic property of these proteins.

scholarly journals The Als3 Cell Wall Adhesin Plays a Critical Role in Human Serum Amyloid A1-Induced Cell Death and Aggregation in Candida albicans

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Jiao Gong ◽  
Jian Bing ◽  
Guobo Guan ◽  
Clarissa J. Nobile ◽  
Guanghua Huang
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
Candida Albicans ◽  
Critical Role ◽  
Membrane Integrity ◽  
Cell Aggregation ◽  
Serum Amyloid ◽  
Mouse Serum ◽  
Content Type ◽  
Serum Amyloid A1

ABSTRACT Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1, respectively) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans. At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the present study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1, in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

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