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

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.

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Post-stress bacterial cell death mediated by reactive oxygen species

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901730116 ◽

2019 ◽

Vol 116 (20) ◽

pp. 10064-10071 ◽

Cited By ~ 37

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.

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Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered Gravity

International Journal of Molecular Sciences ◽

10.3390/ijms19092814 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2814 ◽

Cited By ~ 6

Author(s):

Svantje Tauber ◽

Swantje Christoffel ◽

Cora Thiel ◽

Oliver Ullrich

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Immune System ◽

Cellular Response ◽

Cultured Cells ◽

Parabolic Flight ◽

Reactive Oxygen ◽

Oxygen Species ◽

Altered Gravity ◽

Human Immune System

Whereby several types of cultured cells are sensitive to gravity, the immune system belongs to the most affected systems during spaceflight. Since reactive oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of cellular homeostasis, particularly in the cells of the immune system, we investigated the immediate effect of altered gravity on the transcription of 86 genes involved in reactive oxygen species metabolism, antioxidative systems, and cellular response to oxidative stress, using parabolic flight and suborbital ballistic rocket experiments and microarray analysis. In human myelomonocytic U937 cells, we detected a rapid response of 19.8% of all of the investigated oxidative stress-related transcripts to 1.8 g of hypergravity and 1.1% to microgravity as early as after 20 s. Nearly all (97.2%) of the initially altered transcripts adapted after 75 s of hypergravity (max. 13.5 g), and 100% adapted after 5 min of microgravity. After the almost complete adaptation of initially altered transcripts, a significant second pool of differentially expressed transcripts appeared. In contrast, we detected nearly no response of oxidative stress-related transcripts in human Jurkat T cells to altered gravity. In conclusion, we assume a very well-regulated homeostasis and transcriptional stability of oxidative stress-related pathways in altered gravity in cells of the human immune system.

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The Influence of Reactive Oxygen Species in the Immune System and Pathogenesis of Multiple Sclerosis

Autoimmune Diseases ◽

10.1155/2020/5793817 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 2

Author(s):

Mohammad javad Tavassolifar ◽

Mohammad Vodjgani ◽

Zahra Salehi ◽

Maryam Izad

Keyword(s):

Multiple Sclerosis ◽

Reactive Oxygen Species ◽

Immune System ◽

T Cell ◽

Reactive Oxygen ◽

Autoimmune Response ◽

Antioxidant Systems ◽

Enzymatic Antioxidants ◽

Oxygen Species ◽

Nonenzymatic Antioxidants

Multiple roles have been indicated for reactive oxygen species (ROS) in the immune system in recent years. ROS have been extensively studied due to their ability to damage DNA and other subcellular structures. Noticeably, they have been identified as a pivotal second messenger for T-cell receptor signaling and T-cell activation and participate in antigen cross-presentation and chemotaxis. As an agent with direct toxic effects on cells, ROS lead to the initiation of the autoimmune response. Moreover, ROS levels are regulated by antioxidant systems, which include enzymatic and nonenzymatic antioxidants. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Nonenzymatic antioxidants contain vitamins C, A, and E, glutathione, and thioredoxin. Particularly, cellular antioxidant systems have important functions in maintaining the redox system homeostasis. This review will discuss the significant roles of ROS generation and antioxidant systems under normal conditions, in the immune system, and pathogenesis of multiple sclerosis.

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Antioxidant Enzyme Activity in Bacterial Resistance to Nicotine Toxicity by Reactive Oxygen Species

Archives of Environmental Contamination and Toxicology ◽

10.1007/s00244-009-9305-z ◽

2009 ◽

Vol 57 (3) ◽

pp. 456-462 ◽

Cited By ~ 8

Author(s):

Tiejuan Shao ◽

Haiping Yuan ◽

Bo Yan ◽

Zhenmei Lü ◽

Hang Min

Keyword(s):

Reactive Oxygen Species ◽

Enzyme Activity ◽

Antioxidant Enzyme ◽

Bacterial Resistance ◽

Reactive Oxygen ◽

Antioxidant Enzyme Activity ◽

Oxygen Species

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Mathematical modelling of bacterial resistance to multiple antibiotics and immune system response

SpringerPlus ◽

10.1186/s40064-016-2017-8 ◽

2016 ◽

Vol 5 (1) ◽

Cited By ~ 10

Author(s):

Bahatdin Daşbaşı ◽

İlhan Öztürk

Keyword(s):

Immune System ◽

Mathematical Modelling ◽

Bacterial Resistance ◽

System Response ◽

Immune System Response ◽

Multiple Antibiotics

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Vitiligo, reactive oxygen species and T-cells

Clinical Science ◽

10.1042/cs20090603 ◽

2010 ◽

Vol 120 (3) ◽

pp. 99-120 ◽

Cited By ~ 82

Author(s):

Steven J. Glassman

Keyword(s):

Reactive Oxygen Species ◽

T Cells ◽

Immune System ◽

Dominant Role ◽

Scientific Evidence ◽

Oxidant Stress ◽

Reactive Oxygen ◽

World Population ◽

Oxygen Species ◽

Ample Evidence

The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo.

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