scholarly journals Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Felix Wong ◽  
Jonathan M. Stokes ◽  
Bernardo Cervantes ◽  
Sider Penkov ◽  
Jens Friedrichs ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Cell ◽  
Membrane Damage ◽  
Quantitative Model ◽  
Cellular Targets ◽  
Binding Partner ◽  
Bacterial Cell Death ◽  
Molecular Events ◽  
Membrane Defects ◽  
By Products

AbstractBactericidal antibiotics kill bacteria by perturbing various cellular targets and processes. Disruption of the primary antibiotic-binding partner induces a cascade of molecular events, leading to overproduction of reactive metabolic by-products. It remains unclear, however, how these molecular events contribute to bacterial cell death. Here, we take a single-cell physical biology approach to probe antibiotic function. We show that aminoglycosides and fluoroquinolones induce cytoplasmic condensation through membrane damage and subsequent outflow of cytoplasmic contents as part of their lethality. A quantitative model of membrane damage and cytoplasmic leakage indicates that a small number of nanometer-scale membrane defects in a single bacterium can give rise to the cellular-scale phenotype of cytoplasmic condensation. Furthermore, cytoplasmic condensation is associated with the accumulation of reactive metabolic by-products and lipid peroxidation, and pretreatment of cells with the antioxidant glutathione attenuates cytoplasmic condensation and cell death. Our work expands our understanding of the downstream molecular events that are associated with antibiotic lethality, revealing cytoplasmic condensation as a phenotypic feature of antibiotic-induced bacterial cell death.

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.

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