Genomic characterization of lytic bacteriophages targeting genetically diverse Pseudomonas aeruginosa clinical isolates

Nordstrom, Hayley R.; Evans, Daniel R.; Finney, Amanda G.; Westbrook, Kevin J.; Zamora, Paula F.; Hofstaedter, Casey E.; Yassin, Mohamed; Pradhan, Akansha; Iovleva, Alina; Ernst, Robert K.; Bomberger, Jennifer M.; Shields, Ryan K.; Doi, Yohei; Tyne, Daria Van

doi:10.1016/j.isci.2022.104372

Cited by 23 publications

(24 citation statements)

References 47 publications

(73 reference statements)

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“…To date, there are over 700 phages infecting P. aeruginosa isolated and sequenced [ 129 ]. Several studies using phages against P. aeruginosa showed significant decrease in bacterial loads in vitro and ex vivo and improved survival rates in animals [ 126 , 130 , 131 ]. Three phages produced in Georgia are currently commercialized for use in P. aeruginosa sepsis.…”

Section: Alternative Therapiesmentioning

confidence: 99%

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

et al. 2022

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Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents.

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Section: Alternative Therapiesmentioning

confidence: 99%

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

et al. 2022

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“…( Poranen et al, 2008 ; Matsui et al, 2017 ), can be used for biological, plant control, etc., so the isolation of new Pseudomonas phages remains the focus of scholars in recent years ( Rombouts et al, 2016 ), and is mainly biased toward the study of lytic phages ( Hatzopoulos et al, 2016 ). PSA11, LKA1, and some other P. aeruginosa phages ( Huszczynski et al, 2019 ; Nordstrom et al, 2022 ) use LPS as an infection receptor. The polysaccharide lytic enzymes of these P. aeruginosa phages can reduce cytotoxicity and disrupt biofilms, and they may help to develop new narrow-spectrum antibacterial therapies ( Nordstrom et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…PSA11, LKA1, and some other P. aeruginosa phages ( Huszczynski et al, 2019 ; Nordstrom et al, 2022 ) use LPS as an infection receptor. The polysaccharide lytic enzymes of these P. aeruginosa phages can reduce cytotoxicity and disrupt biofilms, and they may help to develop new narrow-spectrum antibacterial therapies ( Nordstrom et al, 2022 ). Pseudomonas lytic phage cocktails can be used for the treatment of animals infected with P. aeruginosa ( Flodman et al, 2019 ), promising to control chronic infections ( Agarwal et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of two homolog phages infecting Pseudomonas aeruginosa

Niu

Xiaobo²,

Shang³

et al. 2022

Front. Microbiol.

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Bacteriophages (phages) are capable of infecting specific bacteria, and therefore can be used as a biological control agent to control bacteria-induced animal, plant, and human diseases. In this study, two homolog phages (named PPAY and PPAT) that infect Pseudomonas aeruginosa PAO1 were isolated and characterized. The results of the phage plaque assay showed that PPAT plaques were transparent dots, while the PPAY plaques were translucent dots with a halo. Transmission electron microscopy results showed that PPAT (65 nm) and PPAY (60 nm) strains are similar in size and have an icosahedral head and a short tail. Therefore, these belong to the short-tailed phage family Podoviridae. One-step growth curves revealed the latent period of 20 min and burst time of 30 min for PPAT and PPAY. The burst size of PPAT (953 PFUs/infected cell) was higher than that of PPAY (457 PFUs/infected cell). Also, the adsorption rate constant of PPAT (5.97 × 10−7 ml/min) was higher than that of PPAY (1.32 × 10−7 ml/min) at 5 min. Whole-genome sequencing of phages was carried out using the Illumina HiSeq platform. The genomes of PPAT and PPAY have 54,888 and 50,154 bp, respectively. Only 17 of the 352 predicted ORFs of PPAT could be matched to homologous genes of known function. Likewise, among the 351 predicted ORFs of PPAY, only 18 ORFs could be matched to genes of established functions. Homology and evolutionary analysis indicated that PPAT and PPAY are closely related to PA11. The presence of tail fiber proteins in PPAY but not in PPAT may have contributed to the halo effect of its plaque spots. In all, PPAT and PPAY, newly discovered P. aeruginosa phages, showed growth inhibitory effects on bacteria and can be used for research and clinical purposes.

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“…Other methods for controlling P. aeruginosa infections implicate the use of bacteriophages whose host specificity and mode of infectivity depend on the interactions between the viral proteins and the surface of the host bacteria. Nodstrom et al proposed bacteriophage therapy as a promising alternative to eradicate biofilms formed by genetically diverse P. aeruginosa clinical strains isolated from cystic fibrosis patients [99]. The lytic Pseudomonas phage LUZ19 targets QS of P. aeruginosa via a QS targeting protein, Qst.…”

Section: Additional Methods For Restricting Pseudomonas Aeruginosa In...mentioning

confidence: 99%

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

et al. 2023

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The opportunistic human pathogen Pseudomonas aeruginosa is the causal agent of a wide variety of infections. This non-fermentative Gram-negative bacillus can colonize zones where the skin barrier is weakened, such as wounds or burns. It also causes infections of the urinary tract, respiratory system or bloodstream. P. aeruginosa infections are common in hospitalized patients for which multidrug-resistant, respectively extensively drug-resistant isolates can be a strong contributor to a high rate of in-hospital mortality. Moreover, chronic respiratory system infections of cystic fibrosis patients are especially concerning, since very tedious to treat. P. aeruginosa exploits diverse cell-associated and secreted virulence factors, which play essential roles in its pathogenesis. Those factors encompass carbohydrate-binding proteins, quorum sensing that monitor the production of extracellular products, genes conferring extensive drug resistance, and a secretion system to deliver effectors to kill competitors or subvert host essential functions. In this article, we highlight recent advances in the understanding of P. aeruginosa pathogenicity and virulence as well as efforts for the identification of new drug targets and the development of new therapeutic strategies against P. aeruginosa infections. These recent advances provide innovative and promising strategies to circumvent infection caused by this important human pathogen.

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Genomic characterization of lytic bacteriophages targeting genetically diverse Pseudomonas aeruginosa clinical isolates

Cited by 23 publications

References 47 publications

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

Isolation and characterization of two homolog phages infecting Pseudomonas aeruginosa

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

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