Synergistic Interactions among
            <i>Burkholderia cepacia</i>
            Complex-Targeting Phages Reveal a Novel Therapeutic Role for Lysogenization-Capable Phages

Lauman, Philip; Dennis, Jonathan J.

doi:10.1128/spectrum.04430-22

Cited by 9 publications

(7 citation statements)

References 72 publications

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“…With the exception of BCC05 and BCC06, the host ranges of bacteriophages of prophage origin were comparable to those of environmental origin, in agreement with previous literature [48,49]. Additionally, identification of phages with varying host ranges and infection dynamics allows for the development of multi-phage cocktails in order to reduce the probability of phage resistance [46].…”

Section: Discussionsupporting

confidence: 87%

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Harnessing the diversity ofBurkholderiaspp. prophages for therapeutic potential

Nordstrom,

Griffith,

Srinivasa

et al. 2024

Preprint

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Burkholderia spp. are often resistant to antibiotics, and infections with these organisms are difficult to treat. A potential alternative treatment for Burkholderia spp. infections is bacteriophage (phage) therapy; however, it can be difficult to locate phages that target these bacteria. Prophages incorporated into the bacterial genome have been identified within Burkholderia spp. and may represent a source of useful phages for therapy. Here we investigate whether prophages within Burkholderia spp. clinical isolates can kill conspecific and heterospecific isolates. Thirty-two Burkholderia spp. isolates were induced for prophage release, and harvested prophages were tested for lytic activity against the same 32 isolates. Lytic phages were passaged and their host ranges were determined, resulting in four unique phages of prophage origin that showed different ranges of lytic activity. We also analyzed the prophage content of 35 Burkholderia spp. clinical isolate genomes, and identified several prophages present in the genomes of multiple isolates of the same species. Finally, we observed that B. cenocepacia isolates were more phage-susceptible than Burkholderia multivorans isolates. Overall, our findings suggest that prophages present within Burkholderia spp. genomes are a potentially useful starting point for the isolation and development of novel phages for use in phage therapy.

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Section: Discussionsupporting

confidence: 87%

“…In contrast to prior studies [46,47], here we performed a systematic screen of lytic phage activity among induced prophages using more than 30 genetically diverse Burkholderia spp. clinical isolates.…”

Section: Discussionmentioning

confidence: 99%

Harnessing the diversity ofBurkholderiaspp. prophages for therapeutic potential

Nordstrom,

Griffith,

Srinivasa

et al. 2024

Preprint

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show abstract

“…For instance, it had a high global virulence index, a high infection efficacy and stability [70]. The same aspect was considered by Lauman and Dennis, who developed novel metrics that showed a strong inverse correlation between lysogen formation and antibacterial activity, thus confirming that certain lysogenic phages may be therapeutically effective [71].…”

Section: B Cepacia Complexmentioning

confidence: 69%

New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis

Scoffone,

Barbieri,

Irudal

et al. 2024

Antibiotics

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People with cystic fibrosis (CF) suffer from recurrent bacterial infections which induce inflammation, lung tissue damage and failure of the respiratory system. Prolonged exposure to combinatorial antibiotic therapies triggers the appearance of multi-drug resistant (MDR) bacteria. The development of alternative antimicrobial strategies may provide a way to mitigate antimicrobial resistance. Here we discuss different alternative approaches to the use of classic antibiotics: anti-virulence and anti-biofilm compounds which exert a low selective pressure; phage therapies that represent an alternative strategy with a high therapeutic potential; new methods helping antibiotics activity such as adjuvants; and antimicrobial peptides and nanoparticle formulations. Their mechanisms and in vitro and in vivo efficacy are described, in order to figure out a complete landscape of new alternative approaches to fight MDR Gram-negative CF pathogens.

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“…In contrast to prior studies [ 46 , 47 ], here we performed a systematic screening of lytic phage activity among induced prophages using more than 30 genetically diverse Burkholderia spp. clinical isolates.…”

Section: Discussionmentioning

confidence: 99%

“…With the exception of BCC05 and BCC06, the host ranges of phages of prophage origin were comparable to those of environmental origin, in agreement with the previous literature [ 48 , 49 ]. Additionally, identification of phages with varying host ranges and infection dynamics allows for the development of multi-phage cocktails in order to reduce the probability of phage resistance [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Harnessing the Diversity of Burkholderia spp. Prophages for Therapeutic Potential

Nordstrom,

Griffith,

Rangachar Srinivasa

et al. 2024

Cells

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Burkholderia spp. are often resistant to antibiotics, and infections with these organisms are difficult to treat. A potential alternative treatment for Burkholderia spp. infections is bacteriophage (phage) therapy; however, it can be difficult to locate phages that target these bacteria. Prophages incorporated into the bacterial genome have been identified within Burkholderia spp. and may represent a source of useful phages for therapy. Here, we investigate whether prophages within Burkholderia spp. clinical isolates can kill conspecific and heterospecific isolates. Thirty-two Burkholderia spp. isolates were induced for prophage release, and harvested phages were tested for lytic activity against the same 32 isolates. Temperate phages were passaged and their host ranges were determined, resulting in four unique phages of prophage origin that showed different ranges of lytic activity. We also analyzed the prophage content of 35 Burkholderia spp. clinical isolate genomes and identified several prophages present in the genomes of multiple isolates of the same species. Finally, we observed that Burkholdera cenocepacia isolates were more phage-susceptible than Burkholderia multivorans isolates. Overall, our findings suggest that prophages present within Burkholderia spp. genomes are a potentially useful starting point for the isolation and development of novel phages for use in phage therapy.

show abstract

Synergistic Interactions among Burkholderia cepacia Complex-Targeting Phages Reveal a Novel Therapeutic Role for Lysogenization-Capable Phages

Abstract: The spread of antimicrobial resistance is an imminent threat to public health around the world. Particularly concerning are species of the Burkholderia cepacia complex (Bcc), which cause life-threatening respiratory infections and are notoriously resistant to antibiotics.

Cited by 9 publications

References 72 publications

Harnessing the diversity ofBurkholderiaspp. prophages for therapeutic potential

Harnessing the diversity ofBurkholderiaspp. prophages for therapeutic potential

New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis

Harnessing the Diversity of Burkholderia spp. Prophages for Therapeutic Potential

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