Temperate phage-antibiotic synergy eradicates bacteria through depletion of lysogens

Al-Anany, Amany M.; Fatima, Rabia; Hynes, Alexander P.

doi:10.1016/j.celrep.2021.109172

Cited by 57 publications

(54 citation statements)

References 77 publications

(105 reference statements)

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“…In the related ‘Induction Mechanism’, which is only applicable to combinations involving phages that are capable of lysogeny, antibiotic-mediated stimulation of the bacterial stress response similarly results in the overexpression of RecA , which subsequently induces prophages to the lytic cycle. Temperate phages and stress-inducing antibiotics, such as ciprofloxacin, can therefore be potently synergistic combinations, since the phage will destroy at least some bacterial targets directly, while lysogenized cells will subsequently be destroyed from within, by induction of their prophages [ 164 , 249 , 251 ]. Importantly, the temperate phages used in such combinations may also have increased the lysis times, and thus burst sizes due to the morphological changes in the targeted bacteria, meaning that the antibacterial effects of the ‘Delayed Lysis’ and ‘Induction’ mechanisms can be challenging to separate when temperate phages are being utilized.…”

Section: Bacteriophage Therapymentioning

confidence: 99%

Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

Lauman

Dennis

2021

Viruses

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The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all aspects of modern medicine. Particularly concerning, yet insufficiently addressed, are the members of the Burkholderia cepacia complex (Bcc), a group of at least twenty opportunistic, hospital-transmitted, and notoriously drug-resistant species, which infect and cause morbidity in patients who are immunocompromised and those afflicted with chronic illnesses, including cystic fibrosis (CF) and chronic granulomatous disease (CGD). One potential solution to the antimicrobial resistance crisis is phage therapy—the use of phages for the treatment of bacterial infections. Although phage therapy has a long and somewhat checkered history, an impressive volume of modern research has been amassed in the past decades to show that when applied through specific, scientifically supported treatment strategies, phage therapy is highly efficacious and is a promising avenue against drug-resistant and difficult-to-treat pathogens, such as the Bcc. In this review, we discuss the clinical significance of the Bcc, the advantages of phage therapy, and the theoretical and clinical advancements made in phage therapy in general over the past decades, and apply these concepts specifically to the nascent, but growing and rapidly developing, field of Bcc phage therapy.

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Section: Bacteriophage Therapymentioning

confidence: 99%

Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

Lauman

Dennis

2021

Viruses

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“…Temperate phages can enter into the lytic cycle by spontaneously switching from lysogeny under physical or chemical environmental cues (UV-light or heat). Recently, Al-Anany et al reported that the temperate phage HK97 and antibiotic ciprofloxacin combined application results in the eradication of bacterial pathogens [177]. This phage-antibiotic synergy (PAS) increases the effectiveness of the phage against several bacterial pathogens [178][179][180][181][182].…”

Section: Temperate Phagesmentioning

confidence: 99%

“…This phage-antibiotic synergy (PAS) increases the effectiveness of the phage against several bacterial pathogens [178][179][180][181][182]. Furthermore, it is a diverse mechanism that does not simply enhance the phage production and operates through the RecA protein, but is also a critical component of the bacterial SOS response [177]. This strategy may somewhat strengthen their candidature for biocontrol agents but it needs serious attention in this regard [183].…”

Section: Temperate Phagesmentioning

confidence: 99%

“…In carrot fields, an antimicrobial resistant pathogen, including the P. aeruginosa (PAO1) encoding cm1A, a chloramphenicol resistant gene, is effectively controlled by the application of a cocktail of four polyvalent phages, such as φYSZ1, φYSZ2, φYSZ3, and φYSZ4 [202]. Phage cocktail therapy in conjunction with other antimicrobial agents, including antibiotics and plant SAR inducers, which help to reduce disease severity, has revolutionized sustainable disease management and received a lot of attention, showing great potential [177,179,181]. Applications of the phage cocktail with acibenzolar-S-methyl (ASM) efficiently reduces the disease incidence of bacterial spot of tomato caused by X. campestris pv.…”

Section: Recent Advances In the Use Of Phage Cocktail Therapies Again...mentioning

confidence: 99%

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Deploying Viruses against Phytobacteria: Potential Use of Phage Cocktails as a Multifaceted Approach to Combat Resistant Bacterial Plant Pathogens

Farooq

Hussain

Shakeel

et al. 2022

Viruses

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Plants in nature are under the persistent intimidation of severe microbial diseases, threatening a sustainable food production system. Plant-bacterial pathogens are a major concern in the contemporary era, resulting in reduced plant growth and productivity. Plant antibiotics and chemical-based bactericides have been extensively used to evade plant bacterial diseases. To counteract this pressure, bacteria have evolved an array of resistance mechanisms, including innate and adaptive immune systems. The emergence of resistant bacteria and detrimental consequences of antimicrobial compounds on the environment and human health, accentuates the development of an alternative disease evacuation strategy. The phage cocktail therapy is a multidimensional approach effectively employed for the biocontrol of diverse resistant bacterial infections without affecting the fauna and flora. Phages engage a diverse set of counter defense strategies to undermine wide-ranging anti-phage defense mechanisms of bacterial pathogens. Microbial ecology, evolution, and dynamics of the interactions between phage and plant-bacterial pathogens lead to the engineering of robust phage cocktail therapeutics for the mitigation of devastating phytobacterial diseases. In this review, we highlight the concrete and fundamental determinants in the development and application of phage cocktails and their underlying mechanism, combating resistant plant-bacterial pathogens. Additionally, we provide recent advances in the use of phage cocktail therapy against phytobacteria for the biocontrol of devastating plant diseases.

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“…However, in enforced phage training, selection is biased toward the phage, for example by countering phageresistant secondary bacterial growth through co-treatment with silver nanoparticles [27] or antibiotics [28]. It is important to distinguish between pseudo-enforced phage training approaches where the effect is temporary and dependent upon the effector, for example using antibiotics to convert lysogenic cycle to lytic in temperate phage [29], and enforced phage training where the induced changes are permanent, for example exposing the phage to a chelating agent [30,31]. In engineered phage training selection is absolutely biased toward the phage as it evolves naturally after engineering.…”

Section: Pros Of Phages Cons Of Phagesmentioning

confidence: 99%

How to Train Your Phage: The Recent Efforts in Phage Training

et al. 2021

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Control of pathogenic bacteria by deliberate application of predatory phages has potential as a powerful therapy against antibiotic-resistant bacteria. The key advantages of phage biocontrol over antibacterial chemotherapy are: (1) an ability to self-propagate inside host bacteria, (2) targeted predation of specific species or strains of bacteria, (3) adaptive molecular machinery to overcome resistance in target bacteria. However, realizing the potential of phage biocontrol is dependent on harnessing or adapting these responses, as many phage species switch between lytic infection cycles (resulting in lysis) and lysogenic infection cycles (resulting in genomic integration) that increase the likelihood of survival of the phage in response to external stress or host depletion. Similarly, host range will need to be optimized to make phage therapy medically viable whilst avoiding the potential for deleteriously disturbing the commensal microbiota. Phage training is a new approach to produce efficient phages by capitalizing on the evolved response of wild-type phages to bacterial resistance. Here we will review recent studies reporting successful trials of training different strains of phages to switch into lytic replication mode, overcome bacterial resistance, and increase their host range. This review will also highlight the current knowledge of phage training and future implications in phage applications and phage therapy and summarize the recent pipeline of the magistral preparation to produce a customized phage for clinical trials and medical applications.

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Temperate phage-antibiotic synergy eradicates bacteria through depletion of lysogens

Cited by 57 publications

References 77 publications

Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

Deploying Viruses against Phytobacteria: Potential Use of Phage Cocktails as a Multifaceted Approach to Combat Resistant Bacterial Plant Pathogens

How to Train Your Phage: The Recent Efforts in Phage Training

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