Skip to main content
. 2019 Jan 25;9(4):2263–2304. doi: 10.1002/ece3.4743

Table 6.

Contributions of modified filamentous phages in detection and control of pathogens in environment

Filamentous phage Modification in filamentous phage Biosensor type and working principle Target biomaterial Sensitivity/specificity References
Phages in theory of environmental sensing: As an agent to develop sensitive biosensor to track pathogens
E2 from fd and 7b1 from M13 phage libraries Expression of Salmonella typhimurium‐specific peptide (VTPPTQHQ) on pVIII Quartz crystal microbalance (QCM):Modified phage immobilized on QCM platform detects the pathogen based on Piezoelectric effect. Salmonella typhimurium Detects 102 cells/ml with a response time of <180 s Olsen et al. (2007)
JRB7, clone from f8/8 landscape phage library Expression of B. antracis‐specific peptide on pVIII Magnetoelastic resonators (ME):Recombinant phage immobilized onto ME platform coated with gold surface binds to antigen B. anthracis spores Detects 103 spores/ml in vitro conditions Shen, Lakshmanan, Mathison, Petrenko, and Chin (2009)
E2 derived from fd landscape phage library Expression of S. typhimurium‐specific peptide on pVIII Magnetoelastic resonators (ME):Phage nanoprobe immobilized on ME detects binding of pathogen as decrease in resonance frequency S. typhimurium Detects 5×102 cfu/ml of pathogen on the surface of tomato Li, Johnson, et al. (2010), Li, Li, et al. (2010)
M13 M13 displaying peptide specific to target pathogen Lithographically patterned nanowire‐electrodeposition (LPNE):Virus functionalized nanowires developed by grafting modified phage on poly 3,4‐ethylenedioxythiophene (PEDOT) would bind specific antigen. Specific antigen on targeted pathogen Detects antigen (20 nM–99 nM) in in vitro and in vivo conditions Arter, Taggart, Mclntire, Penner, and Weiss (2010)
M13 (Phagemid M13KO7) Expression of the reporter gene, alkaline phosphatase on pVIII with the help of helper phage M13KO7 Amperometric Electrochemical Biosensors:Phage immobilized on the electrode detects the target organism in environmental samples based on the activity of reporter enzyme E. coliTG1 Detection of 1 cfu/ml in <3 hr; 10‐fold increase in the sensitivity of the biosensor (due to enzyme activity) as compared to other phage‐based biosensors Neufeld et al. (2005)
M13 Expression of prostate‐specific membrane antigen (PSMA) specific peptide (CALCEF ‐LG) on pVIII Electrochemical impedance spectroscopy (EIS): Electrode developed by covalent binding of phage to the gold surface generates electrical signal on binding of antigen PSMA 120 nM of the target protein Yang et al. (2006)
M13 pH‐responsive cyanine dye (HCyC‐646) is covalently attached to pVIII Near Infrared Fluorescence Ratiometric pH Imaging: A bright pH‐responsive ratiometric imaging platform, developed by ligation of dye to the phage surface, measures the emission signal on pH change Optically diffused tissue Pathogenesis associated changes in acid–base homeostasis are analyzed by pH measurements both intracellularly and through optically diffused tissue2008 Hilderbrand et al. (2008)
Modified M13 Modified pIII binds specifically to target antigens, whereas modified pVIII reacts with signal‐producing gold nanoparticles (Au NPs) Single bioanalytical platform for antigen detection and identification:DNA‐conjugated phage detects (optically/spectroscopically) and identifies the antigen (DNA microarray) Protein detection and identification Real time, reagent free detection of antigen (detection limit 25 fmole) and its identification in a high‐throughput manner Lee, Domaille, and Cha (2012)
R5C2 Expression of streptavidin‐binding peptide NH2–ANRLP CHPQFPCTSHE on pVIII Opto‐fluidic ring resonator (OFRR) – Lab‐on‐Chip device:Phage integrated on OFRR platform acts as a receptor for detection of analyte and enables label‐free detection of the analyte in small volume Protein/DNA/Virus Real‐time detection of protein/DNA (100 pM; Kdapparent 25 pM) and virus particles (2.3 × 103 pfu/ml) Zhu et al. (2008)
A clone from f8/8 landscape phage library Expression of EPRLSPHS peptide on pVIII protein Modified phage displaying unique landscape on its body binds antigen with extremely high efficiency and specificity Spores of Bacillus anthracis Up to 70‐fold high specificity to spores of B. anthracis than other Bacillusspp. Brigati et al. (2004)
Phages in theory of antagonism and biocontrol: As an agent to biocontrol of phytopathogens
M13 Phages encode restriction endonuclease BglII gene (M13R) or λS holin gene (M13S105, M13VIIIS105) Genetically modified (GM) phage as bactericidal agents: Modified phage kills bacterial host without lysis and release of toxin in environment E. coli strain MC4100F¢ >99% killing of pathogen within 2 hr Hagens and Bläsi (2003)
Pf3 Phage export protein gene is replaced with BglII endonuclease gene Nonreplicating GM phage as bactericidal agents:Modified phage kills host bacteria without lysis and release of endotoxins Pseudomonas aeruginosa Phage treatment effectively control P. aeruginosa population in in vivo condition with a minimal lethal dose Hagens, Habel, von Ahsen, von Gabain, and Blasi (2004)
Nonlytic, M13 phagemid Encode the addiction toxins modules (Gef and ChpBK) Recombinant Phage as a Lethal‐Agent Delivery Vehicle:Modified phage delivers addiction toxins module to elicit programmed cell death in bacterial host E. coli ER2738 94%–98% reduction in in vivo condition within 5 hr Westwater et al. (2003)
M13mp18 phage Expression of genes (csrA and ompF) that target multiple antibiotics simultaneously Adjuvant therapy to treat antibiotic‐resistant bacteria:Modified phages trigger SOS and non‐SOS gene networks that are not directly targeted by antibiotics (e.g., aminoglycosides and β‐lactams) kills antibiotic‐resistant bacteria, biofilm cells, and persister cells E. coli EMG2 and RFS289 Modified phage kills antibiotic‐resistant bacteria, biofilm cells, and persister cells Lu and Collins (2009)
M13 Predominant expression of three glutamic acid (E3) residues on pVIII Silverized Antimicrobial Phage Fibers: Modified phages immobilized to the fibers electrostatically bind silver ions which on subsequent reduction to metallic silver provide antibacterial properties to the fibers Staphylococcus epidermidis and E. coli Biocidal fibers show bactericidal activity up to 300 □m distance within a 2 hr exposure; kills 109 cfu/ml with 20 hr continued exposure Mao, Belcher, and Van Vliet (2010)
fRSM (φRSM1 or φRSM3) Phages found in natural association with host bacteria R. solanacearum MAFF 106603 and MAFF106611 Phage therapy reduces virulence of phytopathogen: Phage‐infected host cells are characterized with reduction in: (i) twitching motility; (ii) number of type IV pili (Tfp); (iii) β‐1,4‐endoglucanase (Egl) activity; (iv) extracellular polysaccharide (EPS) production, and (iii) expression of certain genes (egl, pehC, phcA, phcB, pilT, and hrpB). R. solanacearum MAFF 106603 and MAFF 106611 Loss of virulence to cause wilting to tomato plant (105 cfu wild type trigger wilting within 3 days and cause plant death within 5–7 days) Addy et al. (2012a)
φXacF1 Phage found in natural association with host bacteria X. axonopodis pv. citri MAFF673010 and MAFF301080 Phage therapy reduces virulence of pathogen:φXacF1‐infected X. axonopodis pv. citri strains are characterized with lower levels of extracellular polysaccharide production, reduced twitching motility, slower growth rate, and a dramatic reduction in virulence. X. axonopodis pv. citri MAFF673010 and MAFF301080 Extreme reduction in virulence, failed to cause citrus canker in lemon even after 4 weeks of post‐infection Ahmad et al. (2014)