Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

Bach, Michelle S.; Vries, Christiaan R. de; Khosravi, Arya; Sweere, Johanna M.; Popescu, Medeea; Chen, Qingquan; Demirdjian, Sally; Hargil, Aviv; Belleghem, Jonas Van; Kaber, Gernot; Hajfathalian, Maryam; Burgener, Elizabeth B.; Liú, Dan; Tran, Quynh-Lam; Dharmaraj, Tejas; Birukova, Maria; Sunkari, Vivekananda Gupta; Balaji, Swathi; Ghosh, Nandini; Mathew-Steiner, Shomita S.; Masry, Mohamed S. El; Keswani, Sundeep G.; Banaei, Niaz; Nedelec, Laurence; Sen, Chandan K.; Chandra, Venita; Secor, Patrick R.; Suh, Gina A.; Bollyky, Paul L.

doi:10.1016/j.xcrm.2022.100656

Cited by 21 publications

(23 citation statements)

References 56 publications

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“…One clinical trial (NCT04636554) on personalized phage therapy in patients with COVID-19 and bacterial co-infection (including P. aeruginosa bacteremia/sepsis) is currently ongoing [ 132 ]. There are various case reports in humans showing clearance of P. aeruginosa using single or cocktail phage therapy in numerous infections, namely pressure ulcers with bacteremia [ 133 ], chronic wounds [ 134 ], chronic otitis [ 135 ], venous leg ulcers [ 136 ], and vascular graft infection [ 137 ]. Phage therapy was also combined with antibiotics (phage-antibiotic synergy) to increase bacterial killing of MDR P. aeruginosa in vitro [ 138 , 139 ].…”

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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“…Pf4 virions serve as structural components of biofilm matrices that protect bacteria from antibiotics and desiccation [ 9 , 14 , 15 ]. Pf4 virions also engage immune receptors on macrophages to decrease phagocytic uptake [ 10 , 16 ] and inhibit CXCL1 signaling in keratinocytes, which interferes with wound re-epithelialization [ 17 ]. These observations outline the diverse ways that Pf4 virions promote the initiation and maintenance of P .…”

Section: Introductionmentioning

confidence: 99%

Tripartite interactions between filamentous Pf4 bacteriophage, Pseudomonas aeruginosa, and bacterivorous nematodes

et al. 2023

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The opportunistic pathogen Pseudomonas aeruginosa PAO1 is infected by the filamentous bacteriophage Pf4. Pf4 virions promote biofilm formation, protect bacteria from antibiotics, and modulate animal immune responses in ways that promote infection. Furthermore, strains cured of their Pf4 infection (ΔPf4) are less virulent in animal models of infection. Consistently, we find that strain ΔPf4 is less virulent in a Caenorhabditis elegans nematode infection model. However, our data indicate that PQS quorum sensing is activated and production of the pigment pyocyanin, a potent virulence factor, is enhanced in strain ΔPf4. The reduced virulence of ΔPf4 despite high levels of pyocyanin production may be explained by our finding that C. elegans mutants unable to sense bacterial pigments through the aryl hydrocarbon receptor are more susceptible to ΔPf4 infection compared to wild-type C. elegans. Collectively, our data support a model where suppression of quorum-regulated virulence factors by Pf4 allows P. aeruginosa to evade detection by innate host immune responses.

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“…Phage DNA fragments were detected in the blood hours after phage DNA feeding. With PCR and by in situ DNA hybridization phage DNA was detected in white blood, spleen and liver cells and cloning experiments purportedly showed the integration of phage DNA into a mouse DNA (Schubbert et al) [45] . Other geneticists (Science : Can DNA in food find its way into cells?…”

Section: Bacterial Viruses Interacting With the Mammalian Hostmentioning

confidence: 99%

The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome

Brüssow¹

2023

Microbiome Res Rep

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The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch’s postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease – in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.

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Filamentous bacteriophage delays healing of Pseudomonas-infected wounds

Cited by 21 publications

References 56 publications

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis

Tripartite interactions between filamentous Pf4 bacteriophage, Pseudomonas aeruginosa, and bacterivorous nematodes

The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome

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