Phage therapy: the Escherichia coli experience

Brüssow, Harald

doi:10.1099/mic.0.27849-0

Cited by 243 publications

(164 citation statements)

References 75 publications

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“…Adsorption assays were performed in LB supplemented with 1 mM MgSO 4 and CaCl 2 prewarmed to 37°C, and 1% (wt/vol) type II porcine gastric mucin (Sigma). E. coli B cells (1 × 10 7 CFU mL -1 ) were added to adsorption tubes, vortexed, and CFU titered on LB agar plates at 37°C overnight to ensure accurate bacterial quantification.…”

Section: Methodsmentioning

confidence: 99%

“…Being exposed to the environment, mucosal surfaces are also the infection sites for many important bacterial diseases, including acute diarrhea and cystic fibrosis in humans. This, combined with their accessibility, make mucosal surfaces attractive venues for phage therapy; that is, the use of bacteriophages (phages) to treat and clear bacterial infections (3,4). Clinical success so far has been erratic (5).…”

mentioning

confidence: 99%

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Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters

Barr

Auro

Sam-Soon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

181

186

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Bacteriophages (phages) defend mucosal surfaces against bacterial infections. However, their complex interactions with their bacterial hosts and with the mucus-covered epithelium remain mostly unexplored. Our previous work demonstrated that T4 phage with Hoc proteins exposed on their capsid adhered to mucin glycoproteins and protected mucus-producing tissue culture cells in vitro. On this basis, we proposed our bacteriophage adherence to mucus (BAM) model of immunity. Here, to test this model, we developed a microfluidic device (chip) that emulates a mucosal surface experiencing constant fluid flow and mucin secretion dynamics. Using mucus-producing human cells and Escherichia coli in the chip, we observed similar accumulation and persistence of mucus-adherent T4 phage and nonadherent T4Δhoc phage in the mucus. Nevertheless, T4 phage reduced bacterial colonization of the epithelium >4,000-fold compared with T4Δhoc phage. This suggests that phage adherence to mucus increases encounters with bacterial hosts by some other mechanism. Phages are traditionally thought to be completely dependent on normal diffusion, driven by random Brownian motion, for host contact. We demonstrated that T4 phage particles displayed subdiffusive motion in mucus, whereas T4Δhoc particles displayed normal diffusion. Experiments and modeling indicate that subdiffusive motion increases phage-host encounters when bacterial concentration is low. By concentrating phages in an optimal mucus zone, subdiffusion increases their host encounters and antimicrobial action. Our revised BAM model proposes that the fundamental mechanism of mucosal immunity is subdiffusion resulting from adherence to mucus. These findings suggest intriguing possibilities for engineering phages to manipulate and personalize the mucosal microbiome.BAM | virus | mucus | subdiffusion | search strategy I n all animals, mucosal surfaces provide critical immunological services by both protecting against invading bacterial pathogens and supporting large communities of commensal microorganisms (1, 2). Being exposed to the environment, mucosal surfaces are also the infection sites for many important bacterial diseases, including acute diarrhea and cystic fibrosis in humans. This, combined with their accessibility, make mucosal surfaces attractive venues for phage therapy; that is, the use of bacteriophages (phages) to treat and clear bacterial infections (3,4). Clinical success so far has been erratic (5). The complexities and dynamics of the mucus layer are rarely considered, and the activity of phages therein is mostly unknown. Not surprisingly, phages effective in vitro do not consistently reduce mucosal bacterial host levels in vivo (6, 7). An understanding of the interactions between phages and their bacterial hosts within the relevant physiological environment is critical for consistent success of phage therapy applications.The multilayered mucus is composed primarily of gel-forming mucin glycoproteins that are continually secreted by the underlying epithelium (8). The mucin...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters

Barr

Auro

Sam-Soon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

181

186

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show abstract

“…Therefore, RSA1 itself may be a kind of immunity-deficient or super-infective phage. This property of RSA1 is very important for avoiding the problem of lysogenization by a therapeutic phage, and thus avoids passive import of pathogenicityrelated genes (Merril et al, 2003;Brussow 2005). Compared to cells (strain M4S) without RSA1 sequences, the lysogenic cells (newly established with RSA1-original phage) showed no obvious changes in growth rate, cell morphology, colony morphology, pigmentation, or extracellular polysaccharide production in culture.…”

Section: Rsa Phages Of the Myoviridaementioning

confidence: 99%

Bacteriophages of Ralstonia solanacearum: Their Diversity and Utilization as Biocontrol Agents in Agriculture

Yamada¹

2012

Bacteriophages

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“…It has been documented [19] that the Fc fragment does not bind to Ags but acts as initiation of the complement cascade, a process that leads to the lysis of the target cells or mediates phagocytosis [20][21].…”

Section: Discussionmentioning

confidence: 99%

CpG Motif in Phage Genome DNA Enhanced the Efficacy of Phage Therapy by Immunostimulation

Golkar

Jamil²

2012

Cureus

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Phage therapy: the Escherichia coli experience

Cited by 243 publications

References 75 publications

Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters

Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters

Bacteriophages of Ralstonia solanacearum: Their Diversity and Utilization as Biocontrol Agents in Agriculture

CpG Motif in Phage Genome DNA Enhanced the Efficacy of Phage Therapy by Immunostimulation

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