Isolation and Characterisation of Bacteriophage Selective for Key Acinetobacter baumannii Capsule Chemotypes

Soontarach, Rosesathorn; Srimanote, Potjanee; Enright, Mark C.; Blundell‐Hunter, George; Dorman, Matthew J.; Thomson, Nicholas R.; Taylor, Peter W.; Voravuthikunchai, Supayang Piyawan

doi:10.3390/ph15040443

Cited by 19 publications

(17 citation statements)

References 51 publications

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“…Capsules can mask receptors present on the cell surface, and thus act as barriers to phage infection 1 , 2 , 78 . They can also be necessary for phage infection, especially in nearly ubiquitously capsulated species like Serratia 79 , Acinetobacter 21 or Klebsiella 24 . The host range of capsule-targeting phages is generally restricted to one or a few serotypes 17 , 24 because they rely on the tail spike proteins harbouring depolymerase enzymes 19 , 28 .…”

Section: Discussionmentioning

confidence: 99%

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Haudiquet,

Le Bris,

Nucci

et al. 2024

Nat Commun

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Bacterial evolution is affected by mobile genetic elements like phages and conjugative plasmids, offering new adaptive traits while incurring fitness costs. Their infection is affected by the bacterial capsule. Yet, its importance has been difficult to quantify because of the high diversity of confounding mechanisms in bacterial genomes such as anti-viral systems and surface receptor modifications. Swapping capsule loci between Klebsiella pneumoniae strains allowed us to quantify their impact on plasmid and phage infection independently of genetic background. Capsule swaps systematically invert phage susceptibility, revealing serotypes as key determinants of phage infection. Capsule types also influence conjugation efficiency in both donor and recipient cells, a mechanism shaped by capsule volume and conjugative pilus structure. Comparative genomics confirmed that more permissive serotypes in the lab correspond to the strains acquiring more conjugative plasmids in nature. The least capsule-sensitive pili (F-like) are the most frequent in the species’ plasmids, and are the only ones associated with both antibiotic resistance and virulence factors, driving the convergence between virulence and antibiotics resistance in the population. These results show how traits of cellular envelopes define slow and fast lanes of infection by mobile genetic elements, with implications for population dynamics and horizontal gene transfer.

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Section: Discussionmentioning

confidence: 99%

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Haudiquet,

Le Bris,

Nucci

et al. 2024

Nat Commun

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show abstract

“…Capsules can mask receptors present on the cell surface, and thus act as barriers to phage infection [85][86][87]. They can also be necessary for phage infection, especially in nearly ubiquitously capsulated species like Serratia [88], Acinetobacter [89] or Klebsiella [24]. The host range of capsule targeting phages is generally restricted to one or a few serotypes [24,90], because they rely on the tail spike proteins harbouring depolymerase enzymes [91,92] that act as specific receptor-binding proteins tunnelling through capsules [93].…”

Section: Discussionmentioning

confidence: 99%

“…In many cases phages are blocked by the obstacle caused by the capsule and cannot reach their cell receptor [2,16]. Yet, some phages have evolved mechanisms to bypass the capsule barrier, such as encoding hydrolases called depolymerases which digest the capsule [17][18][19][20][21][22]. Such phages can recognize and attach to capsules of the serotype for which they encode a depolymerase.…”

Section: Graphical Abstract Introductionmentioning

confidence: 99%

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Haudiquet

Nucci

Bris

et al. 2023

Preprint

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Bacterial evolution is affected by mobile genetic elements such as phages and conjugative plasmids, which may provide novel adaptive traits but also incur in fitness costs. Infection by these elements is affected by the bacterial capsule. Yet, its importance has been difficult to quantify and characterise because of the high diversity of bacterial genomes regarding confounding mechanisms such as anti-viral systems. We swapped capsule loci between Klebsiella pneumoniae strains to quantify their effect on transfer of conjugative plasmids and phages independently of the genetic background. Capsule swaps systematically invert phage susceptibility, demonstrating that serotypes are key determinants of phage infection. Capsule types also affect conjugation efficiency in both donor and recipient cells depending on the serotype, a mechanism shaped by the capsule volume and depending on the structure of the conjugative pilus. Comparative genomics confirmed that more permissive serotypes in the lab correspond to the strains acquiring more conjugative plasmids in nature. The pili least sensitive to capsules (F-like) are also the most frequent in the species' plasmids, and are the only ones associated with both antibiotic resistance and virulence factors, driving the convergence between virulence and antibiotics resistance in the population. These results show how the traits of cellular envelopes define slow and fast lanes of infection by mobile genetic elements, with implications for population dynamics and horizontal gene transfer.

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“…There was no phage activity at extreme conditions of temperature (<21°C and >45°C) and pH (<6 and >8). Studies have reported that viability at pH<4 and >9 and temperatures < 15°C is one of the most common limiting factors for phage activity 20,21 . Phages are generally more temperature and pH-resistant compared to their host bacteria 22 .…”

Section: Fig 3: Effect Of Different Temperatures On the Stability And...mentioning

confidence: 99%

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2022

IJPSR

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Phage therapy has become a successful alternative to conventional antibiotic therapy due to the increasing number of multidrug-resistant bacteria in most clinical settings. Various factors like phage adsorption to the host site and phage neutralization by the host determine the efficacy of phage treatment. However, external factors like temperature and pH are critical in deciding the success of using phages in therapeutics. The high stability of phages under both favourable and unfavourable conditions guides their stability in phage therapeutic preparations as well as at the site of infection. In the present study, we exposed the phage to different pH and temperature combinations. The phage showed statistically significant activity at pH 7 and 8 compared to pH 6. In terms of different exposure temperatures, the phage showed good antibacterial activity at temperatures between 31 0 C and 40 0 C. A combination of pH 7 with temperature 38 0 C showed the highest recovery of the phage; however, stability was seen in a considerable range of temperature and pH. The lytic activity of phage was insignificant at extremes of temperature and pH. The present study results indicate that phages, in terms of their stability to variations in external factors, can be a promising alternative to antibiotics or can be used in combination with antibiotics for the successful treatment of multidrug-resistant pathogens. INTRODUCTION:Phage therapy was a popular treatment choice for many infections before the discovery of antibiotics 1 . The recent rise in the number of multidrug-resistant bacteria due to the reduced efficacy of antibiotics has posed a serious challenge for treatment. Due to this and a decline in the number of newer antibiotics in the pipeline, renewed interest has emerged among researchers to revisit the use of phages to treat infections, especially those that are refractory to treatment with most routine and high-level antibiotics 1, 2 .

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Isolation and Characterisation of Bacteriophage Selective for Key Acinetobacter baumannii Capsule Chemotypes

Cited by 19 publications

References 51 publications

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

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