The following press release from the Royal Swedish Academy of Sciences

describes Luria’s work:

Around 1940, Delbrück, Hershey and Luria became interested in bacteriophage, a
type of virus that infects bacteria, rather than ordinary cells. They were trying to
find a living system as simple as possible, on which to study, fundamental life
processes, first of all self-replication. Bacteriophage soon revealed itself to be an
object of choice for such research.

Bacteriophages have served and continue to serve as models for the more
complicated and less approachable systems represented by animal and
human cells. Delbrück, Hershey and Luria have set the solid foundations on
which modern molecular biology rests. Without their contributions the explosive
development of this field would have been hardly possible.

From the medical point of view, the discoveries for which the award is now given
first of all imply a deeper insight into the nature of viruses and of virus
diseases. Indirectly they also bring about an increased understanding of the
mechanism of inheritance and of those mechanisms that control the
development growth and function of tissues and organs.
PREMIO NOBEL 1969
“The properties of bacteriophages have frequently
paved the way for major discoveries in biology and
medicine.”
Microbe 1(4): 164-165, 2006

Researchers are approaching phage with renewed

interest, seeking to use them in agriculture and also
to treat human infections.
(ASM News, 71(10): 453-455, 2005).
ALGUNOS EJEMPLOS SOBRE EL POSIBLE USO DE BACTERIOFAGOS
EN AGRICULTURA Y MEDICINA

- T4 phages against Escherichia coli diarrhea: potential and problems.

Orally applied T4 phages were found with high titers in the cecum and colon
and lower titers in the small intestine, but were not detected in the blood, liver
or spleen. No adverse effects were observed. Virology 2009. 25;388(1):21-30.

- Efficacy of a broad host range lytic bacteriophage against E. coli adhered

to urothelium. Persistent urinary tract infections are often caused by E. coli
adhered to urothelium. The bacteriophage used caused a 45% reduction of the
bacterial population after 2 h of treatment.Curr. Microbiol.2011.62:1128-32.

- Bacteriophages reduce experimental contamination of hard surfaces,

tomato, spinach, broccoli, and ground beef by Escherichia coli O157:H7.
Treatment with the least concentrated phage preparation that elicited
significantly less contamination of the hard surfaces also significantly reduced
the number of viable E. coli O157:H7 organisms on the four food samples.
Appl Environ. Microbiol. 2008 Oct;74(20):6230-8.
Phages recovered from a water treatment plant proved as
effective as chlorine at fighting biofilms, and used in
conjuction with chlorine were more effective than chlorine
alone. Microbe 8, 4-5, 2013
Figure 3. P. aeruginosa
biofilm structure changes
after treatments with P.
aeruginosa phages
(1.9108 PFU/mL, 1 h
treatment only on Day 0),
chlorine (200 mg/L,
continuous
treatment), and their
combination (phage
infection followed by
chlorination). Shiny
surfaces indicate clean
areas with no biofilm
attachment.

Biotechnology and
Bioengineering, Vol.
110,286-295, 2013
Figure 5. Transmission electron microscopic images of biofilm subcellular
structures after the phage and chlorine treatment. Control (a); chlorine
treatment only (b); phage treatment only (c); A combined treatment with
phages and chlorine (d). Bar scale = 0.5 µm.
Biotechnology and Bioengineering, Vol. 110,286-295, 2013
MOLECULAR BIOLOGY, DAVID FREIFELDER
MOLECULAR BIOLOGY, DAVID FREIFELDER
Phage T5 with released DNA, an empty phage head bound through its
tail to a receptor particle (center), and the intact phage not bound to a
receptor particle (top) . J Bacteriol. 2009 June; 191(11): 3431–3436.
Structural components of the T4 particle. Features of the particle have been
resolved to about 3 nm. The positions of several head, tail, baseplate,
and tail fiber proteins are indicated. MMBR 67(1): 86-156, 2003
MICROBIOLOGY, DAVIES-DULBECCO-EISEN-GINSBERG
Electron micrographs of bacteriophage T4. (A) Extended tail fibers recognize the bacterial
envelope, and its prolate icosahedral head contains the 168,903-bp dsDNA genome. (B)
The DNA genome is delivered into the host through the internal tail tube, which is visible
protruding from the end of the contracted tail sheath.
Microbiology & Molecular Biology Reviews 67(1): 86-156, 2003
MICROBIOLOGY, DAVIES-DULBECCO-EISEN-GINSBERG
 CICLO DE MULTIPLICACION

1. ADSORCION. (2-4 MINUTOS)

- ES ESPECIFICA (RECEPTORES EN LA SUPERFICIE DE LA BACTERIA).
- DESORGANIZACION DE LA MEMBRANA PLASMATICA-REVERSIBLE
SE BLOQUEA LA SUPERINFECCION POR FAGOS DEL MISMO TIPO.
- DISTURBIOS METABOLICOS.
- REARREGLO EN LA SINTESIS DE MACROMOLECULAS: SE INHIBE LA
SINTESIS DE DNA, RNA Y PROTEINAS DE LA BACTERIA.

2. PENETRACION
EXPERIMENTO DE HERSHEY Y CHASE
GENES VI, BENJAMIN LEWIN
EXPERIMENTO 1.

3 MINUTOS CENTRIFUGAR 90% 35S

AGITAR SOBRENADANTE
A 2000 RPM

10% 35S
BACTERIA
E. coli
+
35
FAGO T4 ( S )

EXPERIMENTO 2.

3 MINUTOS CENTRIFUGAR ~0% 32P

AGITAR SOBRENADANTE
A 2000 RPM

100% 32P
BACTERIA
E. coli
+
32
FAGO T4 ( P )
MOLECULAR BIOLOGY, DAVIS FREIFELDER
CELL 118(4): 419-429, 2004
Figure 5. Baseplate Conformational Switch Schematics
(A and B) The phage is free in solution. The long tail fibers are extended and
oscillate around their midpoint position. The movements of the fibers are
indicated with black arrows. The proteins are labeled with their corresponding
gene numbers and colored as in Figure 1A. Domains of gp7 and gp10 are
labeled as in Figure 2A.
(C and D) The long tail fibers attach to their surface receptors and adapt the
“down” conformation. The fiber labeled “A” and its corresponding attachment
protein gp9 interact with gp11 and with gp10, respectively. These interactions,
labeled with orange stars, probably initiate the conformational switch of the
baseplate. The black arrows indicate tentative domain movements and
rotations, which have been derived from the comparison of the two terminal
conformations. The fiber labeled “B” has advanced along the conformational
switch pathway so that gp11 is now seen along its 3-fold axis and the short tail
fiber is partially extended in preparation for binding to its receptor. The thick
red arrows indicate the projected movements of the fibers and the baseplate.
(E and F) The conformational switch is complete; the short tail fibers have
bound their receptors and the sheath has contracted. The phage has initiated
DNA transfer into the cell.
Comparison of the Baseplate in the Two Conformations
(A and B) Structure of the periphery of the baseplate in the hexagonal and star
conformations, respectively. Colors identify different proteins as in Figure
1A: gp7 (red), gp8 (blue), gp9 (green), gp10 (yellow), gp11 (cyan), and gp12
(magenta). Three baseplate proteins (gp8, gp9, and gp11), with the available
complete crystal structures, are shown as Cα traces. The density of the short
tail fibers in the star conformation is based on the crystal structure of the
receptor binding, C-terminal fragment of gp12 Thomassen et al. 2003 and on
the corresponding density from the hexagonal conformation of the baseplate.
Directions of the long tail fibers are indicated with gray rods. The three
domains of gp7 are labeled with letters A, B, and C. The four domains of
gp10 are labeled with Roman numbers I through IV. The C-terminal domain
of gp11 is labeled with a black hexagon or black star in the hexagonal or star
conformations, respectively. The baseplate 6-fold axis is indicated by a black
line.
(C and D) Structure of the proteins surrounding the hub in the hexagonal and
star conformations. The proteins are colored as follows: spring green, gp5;
pink, gp19; sky blue, gp27; violet, putative gp48 or gp54; beige, gp6-gp25-
gp53; orange, unidentified protein at the tip of gp5. A part of the tail tube is
shown in both conformations for clarity.
 T-Even Bacteriophage Infecting a Bacteria

http://vimeo.com/10701736
MOLECULAAR BIOLOGY, DAVID FREIFELDER
BACTERIOFAGO PRD1
ASM NEWS 68 (7): 330-335, 2002
BACTERIOFAGO PRD1: INGRESO DEL DNA A LA BACTERIA GRAM-NEGATIVA
OM= MEMBRANA EXTERNA, PG= PEPTIDOGLYCAN, CM= MEMBRANA CITOPLASMATICA
ASM NEWS 68 (7): 330-335, 2002
 CICLO DE MULTIPLICACION

3. SINTESIS DE MACROMOLECULAS VIRALES

- TRANSCRIPCION:
mRNA TEMPRANO: SINTESIS DE PROTEINAS PARA REPLICACION
mRNA TARDIO: SINTESIS DE PROTEINAS ESTRUCTURALES.

- TRADUCCION

- REPLICACION

4. MADURACION Y LIBERACION
GENES VI, BENJAMIN LEWIN
MOLECULAR BIOLOGY, DAVID FREIFELDER
MOLECULAR BIOLOGY, DAVID FREIFELDER
CELL 94(2): 147-150, 1998
Images of Epsilon 15, a virus that infects the bacterium Salmonella. Cross section of the
viral particle's interior, obtained with an advanced magnifier called a cryoelectron
microscope. The right-side is a computer graphic highlighting the salient features of the
virus. Scientists have had difficulty resolving the internal features of viruses with
nonsymmetric components such as Epsilon 15, but Jiang's team made improvements to
the computer software used to process the electron microscopy images. (Graphic
courtesy of Nature magazine/Jiang Laboratories.) Microbe 1(4): 164-165, 2006
CINETICA DE INGRESO DEL DNA

Motor molecular: ATPasas de anillo que convierten energía química en energía mecánica
para introducir 100 pares de bases/segundo. La presión interna maxima es de 60
atmosferas. (fuerza de una molecula de miosina 3-5 pNewtons. Fago 55pNewtons).
Volumen interno de la cabeza del fago φ 29 es 44 nm3; volumen del DNA del 40 nm3
Bustamante y Col., NATURE 413: 748-752, 2001; 421: 423-427, 2003
Viral DNA Packaging-Part I
http://www.youtube.com/watch?v=qKQwK3EB3oc

INTRODUCCION DEL DNA I

Viral DNA Packaging-Part II
http://www.youtube.com/watch?v=H0xdDaWcrdk

INTRODUCCION DEL DNA II

GENES VI, BENJAMIN LEWIN
PHAGE PLAQUES
ADICIONALES
 T-Even Bacteriophage Assembly

http://vimeo.com/10700469