Extending filamentous phage host range by the grafting of a heterologous receptor binding domain

Marzari, Roberto; Sblattero, Daniele; Righi, Massimo; Bradbury, Andrew

doi:10.1016/s0378-1119(96)00623-3

Cited by 52 publications

(31 citation statements)

References 21 publications

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“…Furthermore, additional genetic modifications of filamentous phage to broaden their host range are conceivable. It has been shown that filamentous phage containing chimeric Ike and Ff receptor binding domains attach to E. coli possessing either N or F pili (19). Broadening the host range in this way could be useful for therapeutic purposes.…”

Section: Discussionmentioning

confidence: 99%

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Hagens

Habel

Ahsen

et al. 2004

Antimicrob Agents Chemother

169

111

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Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which mediate the general pathological aspects of septicemia. Here we explored an alternative strategy by using genetically engineered nonreplicating, nonlytic phage to combat an experimental Pseudomonas aeruginosa infection. An export protein gene of the P. aeruginosa filamentous phage Pf3 was replaced with a restriction endonuclease gene. This rendered the Pf3 variant (Pf3R) nonreplicative and concomitantly prevented the release of the therapeutic agent from the target cell. The Pf3R phage efficiently killed a wild-type host in vitro, while endotoxin release was kept to a minimum. Treatment of P. aeruginosa infections of mice with Pf3R or with a replicating lytic phage resulted in comparable survival rates upon challenge with a minimal lethal dose of 3. However, the survival rate after phage therapy with Pf3R was significantly higher than that with the lytic phage upon challenge with a minimal lethal dose of 5. This higher survival rate correlated with a reduced inflammatory response elicited by Pf3R treatment relative to that with the lytic phage. Therefore, this study suggests that the increased survival rate of Pf3R-treated mice could result from reduced endotoxin release. Thus, the use of a nonreplicating modified phage for the delivery of genes encoding proteins toxic to bacterial pathogens may open up a new avenue in antimicrobial therapy.

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Section: Discussionmentioning

confidence: 99%

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Hagens

Habel

Ahsen

et al. 2004

Antimicrob Agents Chemother

169

111

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“…As discussed in Colicin Reception, binding and translocation require the presence of the minor coat capsid protein g3p (or pIII), which is located at the tip of the bacteriophage particle (182,234). Interestingly, like colicins, this protein is organized into three distinct domains separated by flexible glycine-rich linkers, each of them involved in a specific stage of the infection process (361,443,612) (see structural organization section). The functional features of the similar organizations between colicins and g3p proteins were discovered by the construction of active chimeras between the M13 g3p protein and colicin E3 (301).…”

Section: Translocation Of Phage Dnamentioning

confidence: 99%

Colicin Biology

Cascales

Buchanan

Duché

et al. 2007

Microbiol Mol Biol Rev

974

1,324

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SUMMARY Colicins are proteins produced by and toxic for some strains of Escherichia coli. They are produced by strains of E. coli carrying a colicinogenic plasmid that bears the genetic determinants for colicin synthesis, immunity, and release. Insights gained into each fundamental aspect of their biology are presented: their synthesis, which is under SOS regulation; their release into the extracellular medium, which involves the colicin lysis protein; and their uptake mechanisms and modes of action. Colicins are organized into three domains, each one involved in a different step of the process of killing sensitive bacteria. The structures of some colicins are known at the atomic level and are discussed. Colicins exert their lethal action by first binding to specific receptors, which are outer membrane proteins used for the entry of specific nutrients. They are then translocated through the outer membrane and transit through the periplasm by either the Tol or the TonB system. The components of each system are known, and their implication in the functioning of the system is described. Colicins then reach their lethal target and act either by forming a voltage-dependent channel into the inner membrane or by using their endonuclease activity on DNA, rRNA, or tRNA. The mechanisms of inhibition by specific and cognate immunity proteins are presented. Finally, the use of colicins as laboratory or biotechnological tools and their mode of evolution are discussed.

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“…pIII, a phage minor coat protein found on one tip of the virion, accounts for host specificity in both N-pilus (IKE and I2-2)-and F-pilus (Ff)-specific phages (fd, f1, M13) (3,8,11,24). The initial step in Ff phage infection is mediated by the binding of pIII to the tip of the F pilus (19).…”

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confidence: 99%

pIII ^CTX , a Predicted CTXφ Minor Coat Protein, Can Expand the Host Range of Coliphage fd To Include Vibrio cholerae

Heilpern

Waldor

2003

J Bacteriol

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CTX is a filamentous bacteriophage that encodes cholera toxin. CTX infection of its host bacterium, Vibrio cholerae, requires the toxin-coregulated pilus (TCP) and the products of the V. cholerae tolQRA genes. Here, we have explored the role of OrfU, a predicted CTX minor coat protein, in CTX infection. Prior to the discovery that it was part of a prophage, orfU was initially described as an open reading frame of unknown function that lacked similarity to known protein sequences. Based on its size and position in the CTX genome, we hypothesized that OrfU may function in a manner similar to that of the coliphage fd protein pIII and mediate CTX infection as well as playing a role in CTX assembly and release. Deletion of orfU from CTX dramatically reduced the number of CTX virions detected in supernatants from CTX-bearing cells. This defect was complemented by expression of orfU in trans, thereby confirming a role for this gene in CTX assembly and/or release. To evaluate the requirement for OrfU in CTX infection, we introduced fragments of orfU into gIII in an fd derivative to create OrfU-pIII fusions. While fd is ordinarily unable to infect V. cholerae, an fd phage displaying the N-terminal 274 amino acids of OrfU could infect V. cholerae in a TCP-and TolA-dependent fashion. Since our findings indicate that OrfU functions as the CTX pIII, we propose to rename OrfU as pIII CTX . Our data also provide new evidence for a conserved pathway for filamentous phage infection.

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Extending filamentous phage host range by the grafting of a heterologous receptor binding domain

Cited by 52 publications

References 21 publications

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Colicin Biology

pIII ^CTX , a Predicted CTXφ Minor Coat Protein, Can Expand the Host Range of Coliphage fd To Include Vibrio cholerae

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Extending filamentous phage host range by the grafting of a heterologous receptor binding domain

Cited by 52 publications

References 21 publications

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage

Colicin Biology

pIII CTX , a Predicted CTXφ Minor Coat Protein, Can Expand the Host Range of Coliphage fd To Include Vibrio cholerae

Contact Info

Product

Resources

About

pIII ^CTX , a Predicted CTXφ Minor Coat Protein, Can Expand the Host Range of Coliphage fd To Include Vibrio cholerae