Secondary Bacterial Infections During Pulmonary Viral Disease: Phage Therapeutics as Alternatives to Antibiotics?

Manohar, Prasanth; Loh, Belinda; Athira, S.; Nachimuthu, Ramesh; Hua, Xiaoting; Welburn, Susan C.; Leptihn, Sebastian

doi:10.3389/fmicb.2020.01434

Cited by 80 publications

(83 citation statements)

References 93 publications

(109 reference statements)

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“…In addition, the initial immune response to a viral lung infection modifies the respiratory tract microbiome which can, in turn, undermine immune defenses against infections pathogens ( Hanada et al 2018 ). Other inciting mechanisms following viral illnesses include altered epithelial cells that disrupt the mucocilliary clearance and mucus thickening impairing the movement of immune cells ( Manohar et al 2020 ). In the particular setting of SARS-COV 2 infection, fluid and pus filled pulmonairy alveoli creating a nutritive environment for bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus ( Manohar et al 2020 ).…”

Section: Synergy Between Viral and Bacterial Pathogensmentioning

confidence: 99%

“…Other inciting mechanisms following viral illnesses include altered epithelial cells that disrupt the mucocilliary clearance and mucus thickening impairing the movement of immune cells ( Manohar et al 2020 ). In the particular setting of SARS-COV 2 infection, fluid and pus filled pulmonairy alveoli creating a nutritive environment for bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus ( Manohar et al 2020 ).…”

Section: Synergy Between Viral and Bacterial Pathogensmentioning

confidence: 99%

See 1 more Smart Citation

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings

Lucien¹,

Canarie²,

Kilgore³

et al. 2021

International Journal of Infectious Diseases

194

137

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Section: Synergy Between Viral and Bacterial Pathogensmentioning

confidence: 99%

Section: Synergy Between Viral and Bacterial Pathogensmentioning

confidence: 99%

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings

Lucien¹,

Canarie²,

Kilgore³

et al. 2021

International Journal of Infectious Diseases

194

137

View full text Add to dashboard Cite

“…109 Furthermore, increased circulating inflammatory mediators activate coagulation cascades, promoting microcirculatory thrombi formation 110 in addition to promoting acute kidney injury, gastrointestinal inflammation, cardiovascular injury, and cerebrovascular injury. [109][110][111][112][113][114][115] Severe complications observed in COVID-19 patients include respiratory failure, myocardial injury, arrhythmias, stroke, kidney failure, coagulopathy, secondary bacterial infections, and gastrointestinal disease. [111][112][113][114][115] In the early stages of the pandemic, the primary cause of death was thought to be due to ARDS, caused by an excessive and prolonged production of proinflammatory cytokines-a cytokine stormthat caused extensive tissue damage.…”

Section: Coronavirus Pathogenesismentioning

confidence: 99%

SARS‐CoV‐2 infection, COVID‐19 pathogenesis, and exposure to air pollution: What is the connection?

Woodby

Arnold

Valacchi

2020

Annals of the New York Academy of Sciences

125

113

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Exposure to air pollutants has been previously associated with respiratory viral infections, including influenza, measles, mumps, rhinovirus, and respiratory syncytial virus. Epidemiological studies have also suggested that air pollution exposure is associated with increased cases of SARS-CoV-2 infection and COVID-19-associated mortality, although the molecular mechanisms by which pollutant exposure affects viral infection and pathogenesis of COVID-19 remain unknown. In this review, we suggest potential molecular mechanisms that could account for this association. We have focused on the potential effect of exposure to nitrogen dioxide (NO 2), ozone (O 3), and particulate matter (PM) since there are studies investigating how exposure to these pollutants affects the life cycle of other viruses. We have concluded that pollutant exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability. We believe that exposure to pollutants skews adaptive immune responses toward bacterial/allergic immune responses, as opposed to antiviral responses. Exposure to air pollutants could also predispose exposed populations toward developing COIVD-19associated immunopathology, enhancing virus-induced tissue inflammation and damage.

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“…The inherent physicochemical properties of bacteriophages allow bacteriophages to access sites of infection that may not be accessible by chemical compounds. Other properties such as strong bactericidal activity and low intrinsic toxicity of bacteriophages make phage therapy the favourable choice over conventional antibiotics (21,22,23,24). Phages usually infect a limited range of bacteria due to their high specificity and selectivity.…”

Section: Bacteriophages and Phage Therapymentioning

confidence: 99%

Encapsulation and Delivery of Therapeutic Phages

Loh

Gondil

Manohar

et al. 2021

Appl Environ Microbiol

Self Cite

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Delivery of therapeutic compounds to the site of action is crucial. While many chemical substances such as beta-lactam antibiotics can reach therapeutic levels in most parts throughout the human body after administration, substances of higher molecular weight such as therapeutic proteins may not be able to reach the site of action (e.g. an infection), and are therefore ineffective. In the case of therapeutic phages, i.e. viruses that infect microbes that can be used to treat bacterial infections, this problem is exacerbated; not only are phages unable to penetrate tissues, but phage particles can be cleared by the immune system and phage proteins are rapidly degraded by enzymes or inactivated by the low pH in the stomach. Yet, the use of therapeutic phages is a highly promising strategy, in particular for infections caused by bacteria that exhibit multi-drug resistance. Clinicians increasingly encounter situations where no treatment options remain available for such infections, where antibiotic compounds are ineffective. While the number of drug-resistant pathogens continues to rise due to the overuse and misuse of antibiotics, no new compounds are becoming available as many pharmaceutical companies discontinue their search for chemical antimicrobials. In recent years, phage therapy has undergone massive innovation for the treatment of infections caused by pathogens resistant to conventional antibiotics. While most therapeutic applications of phages are well described in the literature, other aspects of phage therapy are less well documented. In this review, we focus on the issues that are critical for phage therapy to become a reliable standard therapy and describe methods for efficient and targeted delivery of phages, including their encapsulation.

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Secondary Bacterial Infections During Pulmonary Viral Disease: Phage Therapeutics as Alternatives to Antibiotics?

Cited by 80 publications

References 93 publications

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings

SARS‐CoV‐2 infection, COVID‐19 pathogenesis, and exposure to air pollution: What is the connection?

Encapsulation and Delivery of Therapeutic Phages

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