Characterization of Virulent T4-Like Acinetobacter baumannii Bacteriophages DLP1 and DLP2

Peters, Danielle L.; Davis, C.; Harris, Greg; Zhou, Haoming; Rather, Philip N.; Hrapovic, Sabahudin; Lam, Edmond; Dennis, Jonathan J.; Chen, Wangxue

doi:10.3390/v15030739

Cited by 6 publications

(5 citation statements)

References 83 publications

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“…These species exhibit similarities in their genotypes and phenotypes [48]. The characterization of A. baumannii bacteriophage is increasing due to the increasing popularity of this treatment method [10]. According to Tipton et al [49], the encapsulating bacterium A. baumannii can transition from an aggressive transparent (AV-T) to an aggressive opaque (VIR-O) phase.…”

Section: Discussionmentioning

confidence: 99%

“…Because phages are found everywhere and are only isolated from areas where their host is present, it is very successful to isolate phages that are effective against a variety of opportunistic infections utilizing wastewater. Owing to their widespread prevalence, the very particular, limited chance of resistive cross-over with antibiotics, and diminished influence on the protective gut microbiome, phages are seen as a possible therapy option to address the AMR epidemic [9,10]. Very few antibiotics in the pipeline have reached an advanced stage of clinical testing.…”

Section: Introductionmentioning

confidence: 99%

“…Very few antibiotics in the pipeline have reached an advanced stage of clinical testing. To address the AMR dilemma, innovative alternatives to antibiotics-like the therapeutic use of bacteriophages-need to be further studied [10]. Because they may swiftly pick up novel resistance determinants from their environment, phages specific to A. baumannii contain several fundamental antibiotic resistance mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of lytic bacteriophages specific for antibiotic-resistant Acinetobacter baumannii

Mahmoud,

Taha,

Bassyouni

et al. 2023

Labyrinth: Fayoum Journal of Science and Interdisciplinary Stud

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Almost all conventional antibiotics are no longer effective against the common nosocomial infection Acinetobacter baumannii. Bacteriophage therapy is an effective alternative for bacterial infections resistant to many drugs. In the present study, a lytic bacteriophage, ФEAP, which infects A. baumannii was chosen for characterization. Phage ФEAP described in this research has the ability to lysis A. baumannii that resists 94 % of the used antibiotics. A. baumannii isolated from a resistant wound abscess. When ФEAP alone incubated at different pH values and different temperatures, the phage was stable over a wide pH range (4 to 9) and at extreme temperatures (between 50°C and 60°C). In addition, ФEAP tolerates all concentrations of NaCl solutions used so it shows salinity tolerance and resistance to UV rays. ФEAP has a 94.4 nm icosahedral head and a 302 nm contractile tail. Pure concentrated phage was negatively stained and investigated using transmission electron microscopy (TEM). Electron micrographs showed that the phage belonged to a member of the Myoviridae family and the Caudovirales order.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of lytic bacteriophages specific for antibiotic-resistant Acinetobacter baumannii

Mahmoud,

Taha,

Bassyouni

et al. 2023

Labyrinth: Fayoum Journal of Science and Interdisciplinary Stud

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“…Phage therapy is currently one of the best hopes for the future control of Gram-negative severe infections that are difficult to eradicate with antibiotics [189 ▪ –192 ▪ ]. This form of treatment first requires the availability of phages with lytic capacity for a specific bacterium, in this case, AB, of which more than 100 have been isolated to date [193,194 ▪ –201 ▪ ]. Hospital wastewater can be a good search source of such phages [202 ▪ ].…”

Section: What Are the Alternative Treatments For Acinetobacter Bauman...mentioning

confidence: 99%

How to treat severe Acinetobacter baumannii infections

Bouza,

Muñoz,

Burillo

2023

Current Opinion in Infectious Diseases

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Purpose of review To update the management of severe Acinetobacter baumannii infections (ABI), particularly those caused by multi-resistant isolates. Recent findings The in vitro activity of the various antimicrobial agents potentially helpful in treating ABI is highly variable and has progressively decreased for many of them, limiting current therapeutic options. The combination of more than one drug is still advisable in most circumstances. Ideally, two active first-line drugs should be used. Alternatively, a first-line and a second-line drug and, if this is not possible, two or more second-line drugs in combination. The emergence of new agents such as Cefiderocol, the combination of Sulbactam and Durlobactam, and the new Tetracyclines offer therapeutic options that need to be supported by clinical evidence. Summary The apparent limitations in treating infections caused by this bacterium, the rapid development of resistance, and the serious underlying situation in most cases invite the search for alternatives to antibiotic treatment, the most promising of which seems to be bacteriophage therapy.

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“…In other words, the process of isolating novel phages can incur an increased selection pressure for rapid capsule modulation, at a rate incompatible with commonly applied methods of phage isolation. For A. baumannii, many phages have been found to select for reduced capsule production [29,30], but most phage isolation attempts for AB5075 specifically have resulted in phages targeting capsule negative mutants [31,32], but not the VIR-O state or the wildtype. It is therefore possible that a thicker capsule might directly block phage absorption; a characteristic found in other bacteria with similar capsule properties [33],…”

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confidence: 99%

Environmental differences impactAcinetobacter baumanniiphage isolation and infectivity

Alseth,

Roush,

Irby

et al. 2024

Preprint

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With the global rise of antimicrobial resistance, phage therapy is increasingly re-gaining traction as a strategy to treat bacterial infections. For phage therapy to be successful however, we first need to isolate appropriate candidate phages for both clinical and experimental research. Acinetobacter baumanniiis an opportunistic pathogen known for its ability to rapidly evolve resistance to antibiotics, making it a prime target for phage therapy. Yet phage isolation is often hampered byA. baumannii’s ability to rapidly switch between capsular states. Here, we report the discovery and structural characterisation of a novel lytic phage, Mystique. This phage was initially isolated against the wild-type AB5075: a commonly used clinical model strain against which no phage has previously been readily available for the capsulated form. When screening Mystique on 103 highly diverse isolates ofA. baumannii, we found that it has a broad host range, being able to infect 85.4% of all tested strains when tested on bacterial lawns – a host range which expanded to 91.3% when tested in liquid culture. This variation between solid and liquid environments on phage infectivity was also observed for several other phages in our collection that were assumed unable to infect AB5075, and capsule negative mutants that initially seemed completely resistant to Mystique proved susceptible when assayed in liquid. Overall, through the discovery of a novel phage we demonstrate how environmental differences can drastically impact phage infectivity with important consequences for phage isolation and characterisation efforts.Author summaryBacterial infections caused byAcinetobacter baumanniiare a major global health concern due to high antibiotic resistance, earning it a critical priority pathogen ranking by the WHO. Phage therapy is resurging as a treatment option, with some success againstA. baumannii. However, the wild-type clinical model strain used to assess new therapies lacks an available phage, and isolating phages forA. baumanniiis challenging due to its complex capsule. Here, we report the discovery of a novel lytic phage, Mystique, which exhibits a broad host range, infecting 94 out of 103 testedA. baumanniistrains. We conducted genomic sequencing and structural analysis to fully characterise Mystique. Additionally, we found that the testing environment significantly impacts results; some phages that do not form plaques on bacterial lawns can still infect and amplify in liquid cultures of the same strain. Moreover, mutants resistant to Mystique based on plaque assays were susceptible in liquid culture assays. This work underscores the necessity of a multifaceted approach for phage isolation and characterisation, as traditional phage assays may not be sufficient for studying bacteria-phage dynamics in certain bacteria such asA. baumannii.

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Characterization of Virulent T4-Like Acinetobacter baumannii Bacteriophages DLP1 and DLP2

Cited by 6 publications

References 83 publications

Isolation and characterization of lytic bacteriophages specific for antibiotic-resistant Acinetobacter baumannii

Isolation and characterization of lytic bacteriophages specific for antibiotic-resistant Acinetobacter baumannii

How to treat severe Acinetobacter baumannii infections

Environmental differences impactAcinetobacter baumanniiphage isolation and infectivity

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