scholarly journals Surface-bound reactive oxygen species generating nanozymes for selective antibacterial action

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Gao ◽  
Tianyi Shao ◽  
Yunpeng Yu ◽  
Yujie Xiong ◽  
Lihua Yang
Keyword(s):  
Reactive Oxygen Species ◽  
Mammalian Cells ◽  
Bacterial Resistance ◽  
Reactive Oxygen ◽  
Resistant Bacteria ◽  
Oxygen Species ◽  
Antibiotic Resistant ◽  
Generate Surface ◽  
Inert Substrate ◽  
Silver Palladium

AbstractActing by producing reactive oxygen species (ROS) in situ, nanozymes are promising as antimicrobials. ROS’ intrinsic inability to distinguish bacteria from mammalian cells, however, deprives nanozymes of the selectivity necessary for an ideal antimicrobial. Here we report that nanozymes that generate surface-bound ROS selectively kill bacteria over mammalian cells. This result is robust across three distinct nanozymes that universally generate surface-bound ROS, with an oxidase-like silver-palladium bimetallic alloy nanocage, AgPd0.38, being the lead model. The selectivity is attributable to both the surface-bound nature of ROS these nanozymes generate and an unexpected antidote role of endocytosis. Though surface-bound, the ROS on AgPd0.38 efficiently eliminated antibiotic-resistant bacteria and effectively delayed the onset of bacterial resistance emergence. When used as coating additives, AgPd0.38 enabled an inert substrate to inhibit biofilm formation and suppress infection-related immune responses in mouse models. This work opens an avenue toward biocompatible nanozymes and may have implication in our fight against antimicrobial resistance.

scholarly journals A boronic acid-functionalized phthalocyanine with an aggregation-enhanced photodynamic effect for combating antibiotic-resistant bacteria

2020 ◽  
Vol 11 (22) ◽  
pp. 5735-5739 ◽  
Author(s):  
Eunhye Lee ◽  
Xingshu Li ◽  
Juwon Oh ◽  
Nahyun Kwon ◽  
Gyoungmi Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antibacterial Activity ◽  
Boronic Acid ◽  
Reactive Oxygen ◽  
Resistant Bacteria ◽  
Ros Generation ◽  
Oxygen Species ◽  
Photodynamic Effect ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant

A boronic acid functionalized phthalocyanine displays aggregation-enhanced reactive oxygen species (ROS) generation and excellent photodynamic antibacterial activity.

Mutagenicity of PFOA in Mammalian Cells: Role of Mitochondria-Dependent Reactive Oxygen Species

2011 ◽  
Vol 45 (4) ◽  
pp. 1638-1644 ◽  
Author(s):  
Guoping Zhao ◽  
Jun Wang ◽  
Xiaofei Wang ◽  
Shaopeng Chen ◽  
Ye Zhao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mammalian Cells ◽  
Reactive Oxygen ◽  
Oxygen Species

Activation of the JAK-STAT pathway by reactive oxygen species

1998 ◽  
Vol 275 (6) ◽  
pp. C1640-C1652 ◽  
Author(s):  
Amy R. Simon ◽  
Usha Rai ◽  
Barry L. Fanburg ◽  
Brent H. Cochran
Keyword(s):  
Reactive Oxygen Species ◽  
Mammalian Cells ◽  
Reactive Oxygen ◽  
Buthionine Sulfoximine ◽  
Early Response ◽  
Carcinoma Cells ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Diphenylene Iodonium ◽  
Stat Pathway

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human diseases, including the acute respiratory distress syndrome, Parkinson’s disease, pulmonary fibrosis, and Alzheimer’s disease. In mammalian cells, several genes known to be induced during the immediate early response to growth factors, including the protooncogenes c- fos and c- myc, have also been shown to be induced by ROS. We show that members of the STAT family of transcription factors, including STAT1 and STAT3, are activated in fibroblasts and A-431 carcinoma cells in response to H2O2. This activation occurs within 5 min, can be inhibited by antioxidants, and does not require protein synthesis. STAT activation in these cell lines is oxidant specific and does not occur in response to superoxide- or nitric oxide-generating stimuli. Buthionine sulfoximine, which depletes intracellular glutathione, also activates the STAT pathway. Moreover, H2O2stimulates the activity of the known STAT kinases JAK2 and TYK2. Activation of STATs by platelet-derived growth factor (PDGF) is significantly inhibited by N-acetyl-l-cysteine and diphenylene iodonium, indicating that ROS production contributes to STAT activation in response to PDGF. These findings indicate that the JAK-STAT pathway responds to intracellular ROS and that PDGF uses ROS as a second messenger to regulate STAT activation.

scholarly journals Investigation of bacterial resistance to the immune system response: Cepacian depolymerisation by reactive oxygen species

2012 ◽  
Vol 18 (4) ◽  
pp. 661-671 ◽  
Author(s):  
Bruno Cuzzi ◽  
Paola Cescutti ◽  
Linda Furlanis ◽  
Cristina Lagatolla ◽  
Luisa Sturiale ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Immune System ◽  
Bacterial Resistance ◽  
Reactive Oxygen ◽  
System Response ◽  
Oxygen Species ◽  
Immune System Response

scholarly journals Post-stress bacterial cell death mediated by reactive oxygen species

2019 ◽  
Vol 116 (20) ◽  
pp. 10064-10071 ◽  
Author(s):  
Yuzhi Hong ◽  
Jie Zeng ◽  
Xiuhong Wang ◽  
Karl Drlica ◽  
Xilin Zhao
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Bacterial Resistance ◽  
Reactive Oxygen ◽  
Temperature Sensitive ◽  
Oxygen Species ◽  
Stress Genes ◽  
Primary Stress ◽  
Bacterial Cell Death ◽  
Ros Accumulation

Antimicrobial efficacy, which is central to many aspects of medicine, is being rapidly eroded by bacterial resistance. Since new resistance can be induced by antimicrobial action, highly lethal agents that rapidly reduce bacterial burden during infection should help restrict the emergence of resistance. To improve lethal activity, recent work has focused on toxic reactive oxygen species (ROS) as part of the bactericidal activity of diverse antimicrobials. We report that whenEscherichia coliwas subjected to antimicrobial stress and the stressor was subsequently removed, both ROS accumulation and cell death continued to occur. Blocking ROS accumulation by exogenous mitigating agents slowed or inhibited poststressor death. Similar results were obtained with a temperature-sensitive mutational inhibition of DNA replication. Thus, bacteria exposed to lethal stressors may not die during treatment, as has long been thought; instead, death can occur after plating on drug-free agar due to poststress ROS-mediated toxicity. Examples are described in which (i) primary stress-mediated damage was insufficient to kill bacteria due to repair; (ii) ROS overcame repair (i.e., protection from anti-ROS agents was reduced by repair deficiencies); and (iii) killing was reduced by anti-oxidative stress genes acting before stress exposure. Enzymatic suppression of poststress ROS-mediated lethality by exogenous catalase supports a causal rather than a coincidental role for ROS in stress-mediated lethality, thereby countering challenges to ROS involvement in antimicrobial killing. We conclude that for a variety of stressors, lethal action derives, at least in part, from stimulation of a self-amplifying accumulation of ROS that overwhelms the repair of primary damage.

scholarly journals Ebsulfur Is a Benzisothiazolone Cytocidal Inhibitor Targeting the Trypanothione Reductase of Trypanosoma brucei

2013 ◽  
Vol 288 (38) ◽  
pp. 27456-27468 ◽  
Author(s):  
Jun Lu ◽  
Suman K. Vodnala ◽  
Anna-Lena Gustavsson ◽  
Tomas N. Gustafsson ◽  
Birger Sjöberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Trypanosoma Brucei ◽  
Mammalian Cells ◽  
Reactive Oxygen ◽  
Redox System ◽  
Trypanothione Reductase ◽  
Oxygen Species ◽  
African Trypanosomiasis ◽  
Thiol Redox

Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured parasites. The inhibition of TryR by EbS was irreversible and NADPH-dependent. EbS formed a complex with TryR and caused oxidation and inactivation of the enzyme. EbS was more toxic for T. brucei than for Trypanosoma cruzi, probably due to lower levels of TryR and trypanothione in T. brucei. Furthermore, inhibition of TryR produced high intracellular reactive oxygen species. Hydrogen peroxide, known to be constitutively high in T. brucei, enhanced the EbS inhibition of TryR. The elevation of reactive oxygen species production in parasites caused by EbS induced a programmed cell death. Soluble EbS analogues were synthesized and cured T. brucei brucei infection in mice when used together with nifurtimox. Altogether, EbS and EbS analogues disrupt the trypanothione system, hampering the defense against oxidative stress. Thus, EbS is a promising lead for development of drugs against African trypanosomiasis.

scholarly journals Photodynamic Effects of Novel XF Porphyrin Derivatives on Prokaryotic and Eukaryotic Cells

2005 ◽  
Vol 49 (4) ◽  
pp. 1542-1552 ◽  
Author(s):  
T. Maisch ◽  
C. Bosl ◽  
R.-M. Szeimies ◽  
N. Lehn ◽  
C. Abels
Keyword(s):  
Reactive Oxygen Species ◽  
Antibiotic Resistance ◽  
Reactive Oxygen ◽  
Human Keratinocytes ◽  
Eukaryotic Cells ◽  
Resistance Pattern ◽  
Resistant Bacteria ◽  
Oxygen Species ◽  
Gram Positive ◽  
Methicillin Resistant

ABSTRACT The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to the killing of gram-positive antibiotic-resistant bacteria of the skin uses light in combination with a photosensitizer to induce a phototoxic reaction. Different concentrations (0 to 100 μM) of porphyrin-based photosensitizers (CTP1, XF70, and XF73) and different incubation times (5 min, 1 h, and 4 h) were used to determine phototoxicity against two methicillin-resistant Staphylococcus aureus strains, one methicillin-sensitive S. aureus strain, one methicillin-resistant Staphylococcus epidermidis strain, one Escherichia coli strain, and human keratinocytes and fibroblasts. Incubation with 0.005 μM XF70 or XF73, followed by illumination, yielded a 3-log10 (≥99.9%) decrease in the viable cell numbers of all staphylococcal strains, indicating that the XF drugs have high degrees of potency against gram-positive bacteria and also that the activities of these novel drugs are independent of the antibiotic resistance pattern of the staphylococci examined. CTP1 was less potent against the staphylococci under the same conditions. At 0.005 μM, XF70 and XF73 demonstrated no toxicity toward fibroblasts or keratinocytes. No inactivation of E. coli was detected at this concentration. XF73 was confirmed to act via a reactive oxygen species from the results of studies with sodium azide (a quencher of singlet oxygen), which reduced the killing of both eukaryotic and prokaryotic cells. When a quencher of superoxide anion and the hydroxyl radical was used, cell killing was not inhibited. These results demonstrate that the porphyrin-based photosensitizers had concentration-dependent differences in their efficacies of killing of methicillin-resistant staphylococcal strains via reactive oxygen species without harming eukaryotic cells at the same concentrations.

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