Sepsis, Phages, and COVID-19

Górski, Andrzej; Borysowski, Jan; Międzybrodzki, Ryszard

doi:10.3390/pathogens9100844

Cited by 8 publications

(5 citation statements)

References 60 publications

(73 reference statements)

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“…So the next step in our study is to determine whether the immunomodulatory effect of MMF reduces its potential value against Brucella infection. Indeed, reduced lymphocyte expansion has also been shown to be beneficial in mouse models of sepsis (Górski et al, 2020 ). Also, MMF supports bacterial clearance when combined with antibiotic therapy (Malekinejad et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Combining multi‐omics analysis to identify host‐targeted targets for the control of Brucella infection

Yu,

Yuan,

Guo

et al. 2023

Microbial Biotechnology

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Human infections caused by Brucella (called brucellosis) are among the most common zoonoses worldwide with an estimated 500,000 cases each year. Since chronic Brucella infections are extremely difficult to treat, there is an urgent need for more effective therapeutics. As a facultative intracellular bacterium, Brucella is strictly parasitic in the host cell. Here, we performed proteomic and transcriptomic and metabolomic analyses on Brucella infected patients, mice and cells that provided an extensive “map” of physiological changes in brucellosis patients and characterized the metabolic pathways essential to the response to infection, as well as the associated cellular response and molecular mechanisms. This is the first report utilizing multi‐omics analysis to investigate the global response of proteins and metabolites associated with Brucella infection, and the data can provide a comprehensive insight to understand the mechanism of Brucella infection. We demonstrated that Brucella increased nucleotide synthesis in the host, consistent with increased biomass requirement. We also identified IMPDH2, a key regulatory complex that controls nucleotide synthesis during Brucella infection. Pharmacological targeting of IMPDH2, the rate‐limiting enzyme in guanine nucleotide biosynthesis, efficiently inhibits B. abortus growth both in vitro and in vivo. Through screening a library of natural products, we identified oxymatrine, an alkaloid obtained primarily from Sophora roots, is a novel and selective IMPDH2 inhibitor. In further in vitro bacterial inhibition assays, oxymatrine effectively inhibited the growth of B. abortus, which was impaired by exogenous supplementation of guanosine, a salvage pathway of purine nucleotides. This moderately potent, structurally novel compound may provide clues for further design and development of efficient IMPDH2 inhibitors and also demonstrates the potential of natural compounds from plants against Brucella.

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Section: Discussionmentioning

confidence: 99%

Combining multi‐omics analysis to identify host‐targeted targets for the control of Brucella infection

Yu,

Yuan,

Guo

et al. 2023

Microbial Biotechnology

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“…The first clinical reports from early 2020 highlighted high plasma levels of interleukin-6 (IL-6), IL-1, tumor necrosis factor α (TNF-α), ferritin, and increased amounts of other inflammatory biomarkers. This underlined the assumption that COVID-19 was comparable to sepsis and led to the idea that these biomarker levels were the cause for organ failure and, thus, needed to be suppressed [16][17][18][19][20][21]. Therefore, several clinical trials started using anti-inflammatory therapies to try to reduce the cytokine plasma levels [22][23][24] (Table 2).…”

Section: Covid-19-induced Sepsis Immunotherapies and Antiviral Treatm...mentioning

confidence: 99%

A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis

Brandenburg,

Ferrer-Espada,

Martinez-de-Tejada

et al. 2023

IJMS

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Sepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels.

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“…If bacterial co-infection has been proven or its presence is very likely, PCT reduced by 80% of the baseline value or below 0.5 μg/L after 48 hours or 72 hours, stopping antibiotic administration is reasonable [38]. Finally, phages are very target-specific, have low toxicity and resistance to them are rare, in addition to reducing the synthesis of reactive oxygen species (ROS), whose levels are elevated in COVID-19 patients [46,47].…”

Section: Possible Treatment Alternativesmentioning

confidence: 99%

"Multidrug-Resistant Bacteria Related to Covid-19 Infection: A Minireview"

Rocha Curvelo

2024

BJSTR

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The World Health Organization recorded antimicrobial multidrug resistance as one of the biggest health risks in 2019. The inappropriate use of antibiotics results in their consequent ineffectiveness in the treatment of bacterial infections, hindering therapeutic alternatives and increasing the risk of poor prognosis. In late 2019, a single-stranded RNA zoonotic virus, SARS-CoV-2, was identified and caused the Coronavirus Disease-19 pandemic. The use of antibiotics prophylactically for secondary bacterial infections was one of the measures taken in the emergency scenario. The damage to the airways caused by these viruses and inhibition of the immune system favor bacterial adhesion and growth in the respiratory tract, the lack of knowledge of the disease and the initial symptomatic similarity between bacterial and viral infections, generating controversial diagnosis, causing concern about the impact on the worsening of the global condition of multidrug-resistant bacteria. More research aiming new treatments and control alternatives in cases of bacterial co-infection associated with COVID-19 and its possible markers is needed, as well as investigations of the possible impact of the pandemic on the global scenario of acquired multidrug resistance. Immunization of the population and individual respiratory stabilization effort and measures are still the only known protective measures. In the pandemic scenario characterized by a high use of biocidal agents, empirical and disordered use of antibiotics, decreased surveillance of resistance worldwide and overcrowding of health systems, lack of medical staff and personal protective equipment in some hospitals are factors that have contributed to the increase in antimicrobial resistance incidence. On the other hand, individual protective measures were identified as factors that reduce the incidence of infections in the community. In some countries, the increasing in the incidence of carbapenem-resistant bacteria and new genes and combinations have been reported, which may be related to the COVID-19 pandemic.

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Sepsis, Phages, and COVID-19

Cited by 8 publications

References 60 publications

Combining multi‐omics analysis to identify host‐targeted targets for the control of Brucella infection

Combining multi‐omics analysis to identify host‐targeted targets for the control of Brucella infection

A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis

"Multidrug-Resistant Bacteria Related to Covid-19 Infection: A Minireview"

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