The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections
The life-threatening pandemic concerning multi-drug resistant (MDR) bacteria is an evolving problem involving increased hospitalizations, billions of dollars in medical costs and a remarkably high number of deaths. Bacterial pathogens have demonstrated the capacity for spontaneous or acquired antibi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.639362/full |
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| author | Daniel J. Hassett Rhett A. Kovall Michael J. Schurr Nalinikanth Kotagiri Harshita Kumari Latha Satish Latha Satish |
| author_facet | Daniel J. Hassett Rhett A. Kovall Michael J. Schurr Nalinikanth Kotagiri Harshita Kumari Latha Satish Latha Satish |
| author_sort | Daniel J. Hassett |
| collection | DOAJ |
| description | The life-threatening pandemic concerning multi-drug resistant (MDR) bacteria is an evolving problem involving increased hospitalizations, billions of dollars in medical costs and a remarkably high number of deaths. Bacterial pathogens have demonstrated the capacity for spontaneous or acquired antibiotic resistance and there is virtually no pool of organisms that have not evolved such potentially clinically catastrophic properties. Although many diseases are linked to such organisms, three include cystic fibrosis (CF), burn/blast wounds and urinary tract infections (UTIs), respectively. Thus, there is a critical need to develop novel, effective antimicrobials for the prevention and treatment of such problematic infections. One of the most formidable, naturally MDR bacterial pathogens is Pseudomonas aeruginosa (PA) that is particularly susceptible to nitric oxide (NO), a component of our innate immune response. This susceptibility sets the translational stage for the use of NO-based therapeutics during the aforementioned human infections. First, we discuss how such NO therapeutics may be able to target problematic infections in each of the aforementioned infectious scenarios. Second, we describe a recent discovery based on years of foundational information, a novel drug known as AB569. AB569 is capable of forming a “time release” of NO from S-nitrosothiols (RSNO). AB569, a bactericidal tandem consisting of acidified NaNO2 (A-NO2–) and Na2-EDTA, is capable of killing all pathogens that are associated with the aforementioned disorders. Third, we described each disease state in brief, the known or predicted effects of AB569 on the viability of PA, its potential toxicity and highly remote possibility for resistance to develop. Finally, we conclude that AB569 can be a viable alternative or addition to conventional antibiotic regimens to treat such highly problematic MDR bacterial infections for civilian and military populations, as well as the economical burden that such organisms pose. |
| first_indexed | 2024-12-22T02:57:53Z |
| format | Article |
| id | doaj.art-7f645348c22e47f2bb54b46b5a18dd4b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T02:57:53Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7f645348c22e47f2bb54b46b5a18dd4b2022-12-21T18:41:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-06-011210.3389/fmicb.2021.639362639362The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract InfectionsDaniel J. Hassett0Rhett A. Kovall1Michael J. Schurr2Nalinikanth Kotagiri3Harshita Kumari4Latha Satish5Latha Satish6Department of Molecular Genetics, Biochemistry and Microbiology, Cincinnati, OH, United StatesDepartment of Molecular Genetics, Biochemistry and Microbiology, Cincinnati, OH, United StatesDepartment of Immunology and Microbiology, University of Colorado Health Sciences, Denver, CO, United StatesDivision of Pharmacy, University of Colorado Health Sciences, Denver, CO, United StatesDivision of Pharmacy, University of Colorado Health Sciences, Denver, CO, United StatesDepartment of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesShriners Hospitals for Children—Cincinnati, Cincinnati, OH, United StatesThe life-threatening pandemic concerning multi-drug resistant (MDR) bacteria is an evolving problem involving increased hospitalizations, billions of dollars in medical costs and a remarkably high number of deaths. Bacterial pathogens have demonstrated the capacity for spontaneous or acquired antibiotic resistance and there is virtually no pool of organisms that have not evolved such potentially clinically catastrophic properties. Although many diseases are linked to such organisms, three include cystic fibrosis (CF), burn/blast wounds and urinary tract infections (UTIs), respectively. Thus, there is a critical need to develop novel, effective antimicrobials for the prevention and treatment of such problematic infections. One of the most formidable, naturally MDR bacterial pathogens is Pseudomonas aeruginosa (PA) that is particularly susceptible to nitric oxide (NO), a component of our innate immune response. This susceptibility sets the translational stage for the use of NO-based therapeutics during the aforementioned human infections. First, we discuss how such NO therapeutics may be able to target problematic infections in each of the aforementioned infectious scenarios. Second, we describe a recent discovery based on years of foundational information, a novel drug known as AB569. AB569 is capable of forming a “time release” of NO from S-nitrosothiols (RSNO). AB569, a bactericidal tandem consisting of acidified NaNO2 (A-NO2–) and Na2-EDTA, is capable of killing all pathogens that are associated with the aforementioned disorders. Third, we described each disease state in brief, the known or predicted effects of AB569 on the viability of PA, its potential toxicity and highly remote possibility for resistance to develop. Finally, we conclude that AB569 can be a viable alternative or addition to conventional antibiotic regimens to treat such highly problematic MDR bacterial infections for civilian and military populations, as well as the economical burden that such organisms pose.https://www.frontiersin.org/articles/10.3389/fmicb.2021.639362/fullbactericidalAB569cystic fibrosisburns/woundsurinary tract infections |
| spellingShingle | Daniel J. Hassett Rhett A. Kovall Michael J. Schurr Nalinikanth Kotagiri Harshita Kumari Latha Satish Latha Satish The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections Frontiers in Microbiology bactericidal AB569 cystic fibrosis burns/wounds urinary tract infections |
| title | The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections |
| title_full | The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections |
| title_fullStr | The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections |
| title_full_unstemmed | The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections |
| title_short | The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections |
| title_sort | bactericidal tandem drug ab569 how to eradicate antibiotic resistant biofilm pseudomonas aeruginosa in multiple disease settings including cystic fibrosis burns wounds and urinary tract infections |
| topic | bactericidal AB569 cystic fibrosis burns/wounds urinary tract infections |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.639362/full |
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