A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized<sup>13</sup>C-Urea

Raissy, Hengameh H.; Timmins, Graham S.; Davies, Lea; Heynekamp, Theresa; Harkins, Michelle; Sharp, Zachary D.; Kelly, H. William

doi:10.1089/ped.2015.0619

Cited by 10 publications

(5 citation statements)

References 18 publications

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“…It is associated with urinary tract infection. 378 , 427 None None Outer membrane proteins The outer membrane contains a large number of outer membrane proteins. These protein members are involved in the transportation of amino acids and peptides, the absorption of antibiotics, and the transportation of carbon sources.…”

Section: Virulence Factorsmentioning

confidence: 99%

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Qin

Xiao

Zhou

et al. 2022

Sig Transduct Target Ther

479

323

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Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infection requiring ventilation, such as COVID-19. P. aeruginosa is also a widely-used model bacterium for all biological areas. In addition to continued, intense efforts in understanding bacterial pathogenesis of P. aeruginosa including virulence factors (LPS, quorum sensing, two-component systems, 6 type secretion systems, outer membrane vesicles (OMVs), CRISPR-Cas and their regulation), rapid progress has been made in further studying host-pathogen interaction, particularly host immune networks involving autophagy, inflammasome, non-coding RNAs, cGAS, etc. Furthermore, numerous technologic advances, such as bioinformatics, metabolomics, scRNA-seq, nanoparticles, drug screening, and phage therapy, have been used to improve our understanding of P. aeruginosa pathogenesis and host defense. Nevertheless, much remains to be uncovered about interactions between P. aeruginosa and host immune responses, including mechanisms of drug resistance by known or unannotated bacterial virulence factors as well as mammalian cell signaling pathways. The widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections, especially those caused by multi-drug resistance strains. Benefited from has advancing in research tools and technology, dissecting this pathogen’s feature has entered into molecular and mechanistic details as well as dynamic and holistic views. Herein, we comprehensively review the progress and discuss the current status of P. aeruginosa biophysical traits, behaviors, virulence factors, invasive regulators, and host defense patterns against its infection, which point out new directions for future investigation and add to the design of novel and/or alternative therapeutics to combat this clinically significant pathogen.

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Section: Virulence Factorsmentioning

confidence: 99%

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Qin

Xiao

Zhou

et al. 2022

Sig Transduct Target Ther

479

323

View full text Add to dashboard Cite

show abstract

“…A recent study of a range of clinical CF and non-CF isolates, however, showed urease activity in all, with relatively little variation and no association with virulence [160]. However, the detection of urease activity in the lungs of CF patients colonized with P. aeruginosa [27] shows detectable activity in the lung, even with the potential for downregulation.…”

Section: Pseudomonas Aeruginosamentioning

confidence: 90%

“…We published the first clinical data of the inhaled 13 C-urea breath test in controls and in cystic fibrosis (CF) patients with P. aeruginosa colonization [27]. The increase in exhaled 13 CO 2 after inhalation of nebulized 13 C-urea was dependent both upon P. aeruginosa colonization status and upon 13 C-urea dose.…”

Section: Detection Of Microbial Urease In Vivo In Lung By Breath Testmentioning

confidence: 99%

Potential for breath test diagnosis of urease positive pathogens in lung infections

Bishai

Timmins

2019

J. Breath Res.

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Roles for urease in virulence are accepted for Helicobacter pylori and urinary tract pathogens. However, urease is widely expressed by bacterial and fungal lung pathogens causing emerging and opportunistic lung infections, organisms causing acute exacerbations of chronic bronchitis, mycobacterial lung diseases such as tuberculosis (TB), and ventilator associated pneumonia and health care associated pneumonia. Detection of urease provides a method for rapid in vivo detection of these lung pathogens by inhaled 13C- breath test, and this review discusses the range of lung pathogens that might be amenable to rapid diagnosis.

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“…Then rapid metabolism in situ in the lung generates a rapid signal of 13 CO 2 in breath before urea is systemically absorbed, transported to the GI tract, metabolized to 13 CO 2 which is then transported to the lungs and exhaled- termed the ‘kinetic window’. 17,18 Therefore, there are good reasons why stable isotope tracer breath tests are developed, despite the extra expense and regulatory burdens involved in making and administering a labeled compound to humans.…”

Section: Why Use Stable Isotope Based Breath Tests?mentioning

confidence: 99%

Stable isotope biomarker breath tests for human metabolic and infectious diseases: a review of recent patent literature

Timmins

2016

Expert Opinion on Therapeutic Patents

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Introduction Stable isotope breath tests can rapidly and quantitatively report metabolic phenotypes and disease in both humans and microbes in situ. The labelled compound is administered and acted upon by human or microbial metabolism, producing a labelled gas that is detected in exhaled breath. Areas Covered This review details the unique advantages (and disadvantages) of phenotypic stable isotope based breath tests. A review of recent US patent applications and prosecutions since 2010 is conducted. Finally, current clinical trials, product pipelines and approved products are discussed. Expert Opinion Stable isotope breath tests offer new approaches for rapid and minimally invasive detection and study of metabolic phenotypes, both human and microbial. The patent literature has developed considerably in the last 6 years, with over 30 patent applications made. Rates of issuance remain high, although rejections citing 35 U.S.C. §101(subject matter eligibility), §102 (novelty), §103 (obviousness) and §112 (description, enablement and best mode) have occurred. The prior art is significantly greater for human metabolism than microbial, and may drive differing rates of future issuance. These biomarker and diagnostic tools can enable optimization of drug doses, diagnosis of metabolic disease and its progression, and detection of infectious disease and optimize its treatment.

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A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized¹³C-Urea

Cited by 10 publications

References 18 publications

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Potential for breath test diagnosis of urease positive pathogens in lung infections

Stable isotope biomarker breath tests for human metabolic and infectious diseases: a review of recent patent literature

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A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized13C-Urea

Cited by 10 publications

References 18 publications

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

Potential for breath test diagnosis of urease positive pathogens in lung infections

Stable isotope biomarker breath tests for human metabolic and infectious diseases: a review of recent patent literature

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Product

Resources

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A Proof of Concept Study to Detect Urease Producing Bacteria in Lungs Using Aerosolized¹³C-Urea