Investigating Bacteriophages Targeting the Opportunistic Pathogen Acinetobacter baumannii

Styles, Kathryn M.; Thummeepak, Rapee; Leungtongkam, Udomluk; Smith, Sophie E; Christie, Gabrielle S; Millard, Andrew; Moat, John; Dowson, Christopher G.; Wellington, Elizabeth M. H.; Sitthisak, Sutthirat; Sagona, Antonia P.

doi:10.3390/antibiotics9040200

Cited by 30 publications

(33 citation statements)

References 45 publications

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“…The cells released significantly less lactate dehydrogenase compared with cells not treated with this phage. This confirmed the efficacy of phage and its potential application as a surface antimicrobial agent for use in hospitals [ 114 ]. Another study used a novel approach to prepare personalized therapeutic phage cocktails against the life-threatening MDR infection of A. baumannii in a 68-year-old diabetic patient with necrotic pancreatitis.…”

Section: Personalized Medicine and Clinical Trials Based On Phages (Determining The Safety Of Phage Therapy)supporting

confidence: 66%

Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development

Zalewska-Piątek

Piątek

2021

Pharmaceuticals

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The constantly growing number of people suffering from bacterial, viral, or fungal infections, parasitic diseases, and cancers prompts the search for innovative methods of disease prevention and treatment, especially based on vaccines and targeted therapy. An additional problem is the global threat to humanity resulting from the increasing resistance of bacteria to commonly used antibiotics. Conventional vaccines based on bacteria or viruses are common and are generally effective in preventing and controlling various infectious diseases in humans. However, there are problems with the stability of these vaccines, their transport, targeted delivery, safe use, and side effects. In this context, experimental phage therapy based on viruses replicating in bacterial cells currently offers a chance for a breakthrough in the treatment of bacterial infections. Phages are not infectious and pathogenic to eukaryotic cells and do not cause diseases in human body. Furthermore, bacterial viruses are sufficient immuno-stimulators with potential adjuvant abilities, easy to transport, and store. They can also be produced on a large scale with cost reduction. In recent years, they have also provided an ideal platform for the design and production of phage-based vaccines to induce protective host immune responses. The most promising in this group are phage-displayed vaccines, allowing for the display of immunogenic peptides or proteins on the phage surfaces, or phage DNA vaccines responsible for expression of target genes (encoding protective antigens) incorporated into the phage genome. Phage vaccines inducing the production of specific antibodies may in the future protect us against infectious diseases and constitute an effective immune tool to fight cancer. Moreover, personalized phage therapy can represent the greatest medical achievement that saves lives. This review demonstrates the latest advances and developments in the use of phage vaccines to prevent human infectious diseases; phage-based therapy, including clinical trials; and personalized treatment adapted to the patient’s needs and the type of bacterial infection. It highlights the advantages and disadvantages of experimental phage therapy and, at the same time, indicates its great potential in the treatment of various diseases, especially those resistant to commonly used antibiotics. All the analyses performed look at the rich history and development of phage therapy over the past 100 years.

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Section: Personalized Medicine and Clinical Trials Based On Phages (Determining The Safety Of Phage Therapy)supporting

confidence: 66%

Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development

Zalewska-Piątek

Piątek

2021

Pharmaceuticals

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“…Although such a strategy fits the current trend to personalize medicine and has not only been widely discussed but also successfully used [ 28 ], it is commercially unattractive, as custom-made phage preparations cannot be currently approved for medical use [ 21 , 125 , 126 ]. Moreover, even mixtures of phages of different specificity usually do not exhibit a universal strain range [ 21 , 91 , 127 – 129 ], and searching for natural phages of the missing specificity is tedious, time consuming, and often either fails or leads to the isolation of only temperate phages [ 21 , 90 ]. Even the so called adaptation of phages to infect resistant strains by selection of natural phage mutants has limited potential in the acquisition of phages of new specificities [ 76 , 120 , 130 – 133 ].…”

Section: Engineered Phages As Future Therapeutic Options: Rationale and Perspectivesmentioning

confidence: 99%

Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future

2021

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The current problems with increasing bacterial resistance to antibacterial therapies, resulting in a growing frequency of incurable bacterial infections, necessitates the acceleration of studies on antibacterials of a new generation that could offer an alternative to antibiotics or support their action. Bacteriophages (phages) can kill antibiotic-sensitive as well as antibiotic-resistant bacteria, and thus are a major subject of such studies. Their efficacy in curing bacterial infections has been demonstrated in in vivo experiments and in the clinic. Unlike antibiotics, phages have a narrow range of specificity, which makes them safe for commensal microbiota. However, targeting even only the most clinically relevant strains of pathogenic bacteria requires large collections of well characterized phages, whose specificity would cover all such strains. The environment is a rich source of diverse phages, but due to their complex relationships with bacteria and safety concerns, only some naturally occurring phages can be considered for therapeutic applications. Still, their number and diversity make a detailed characterization of all potentially promising phages virtually impossible. Moreover, no single phage combines all the features required of an ideal therapeutic agent. Additionally, the rapid acquisition of phage resistance by bacteria may make phages already approved for therapy ineffective and turn the search for environmental phages of better efficacy and new specificity into an endless race. An alternative strategy for acquiring phages with desired properties in a short time with minimal cost regarding their acquisition, characterization, and approval for therapy could be based on targeted genome modifications of phage isolates with known properties. The first example demonstrating the potential of this strategy in curing bacterial diseases resistant to traditional therapy is the recent successful treatment of a progressing disseminated Mycobacterium abscessus infection in a teenage patient with the use of an engineered phage. In this review, we briefly present current methods of phage genetic engineering, highlighting their advantages and disadvantages, and provide examples of genetically engineered phages with a modified host range, improved safety or antibacterial activity, and proven therapeutic efficacy. We also summarize novel uses of engineered phages not only for killing pathogenic bacteria, but also for in situ modification of human microbiota to attenuate symptoms of certain bacterial diseases and metabolic, immune, or mental disorders.

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“…While some phages target multiple species or genera, most are highly specific for a single strain [52]. Single phages are highly predisposed to resistance development and therefore are often combined into multiple phage cocktails or, to achieve synergy, administered in combination with small molecule antimicrobial agents [50,[52][53][54][55].…”

Section: Phage Therapies Virulence Inhibitors Bacterial Growth Ratementioning

confidence: 99%

Antibacterial Drug Development: A New Approach Is Needed for the Field to Survive and Thrive

et al. 2020

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It is often said that the marketplace for new antibiotics is broken. This notion is supported by the observation that many recently-approved antibiotics to treat drug-resistant bacteria have failed commercially in a spectacular fashion. Today, companies with peak market-cap values in excess of USD 500 million to 1 billion prior to product launch regularly sell for pennies on the dollar a few years after market introduction. It is possible, however, that the market is not as broken as we perceive. That is, in the collective mind of the clinician, recently-approved antibiotics may be too-poorly differentiated to justify their broad use and inordinate cost relative to those already existing. Perhaps we in the antibacterial drug development field must change our way of thinking if we are to survive and thrive. Rather than reflexively developing new β-lactam-β-lactamase inhibitor combinations for every new enzyme that evades our current inhibitors, we should focus discovery and development efforts on agents that revolutionize how we potentiate antibiotics. To this end, there has been renewed interest in phage therapies, virulence inhibitors, bacterial growth rate modulators, monoclonal antibodies, and other approaches to augment antibiotic effects. Herein, we suggest that the unmet medical need is less about adding poorly-differentiated antibiotics to our armamentarium and more about the need for innovation in how we augment antibiotic regimen effects.

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Investigating Bacteriophages Targeting the Opportunistic Pathogen Acinetobacter baumannii

Cited by 30 publications

References 45 publications

Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development

Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development

Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future

Antibacterial Drug Development: A New Approach Is Needed for the Field to Survive and Thrive

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