LamBAn outer-membrane porin thatis used to transport maltose into bacterial cells. It is also the receptor of phage λ.
Access to host receptors
• Adsorption = the specific interaction between
the phage receptor-binding protein (RBP) + its
bacterial cell surface receptor
• Bacterial receptors (biochemical families) =
surface proteins, polysaccharides and
Adapting to new receptors.
• Tailed phages are able to modify their RBPs to
acquire novel receptor tropism
• phage λ attacks E.coli through cognate receptor
LamB and interaction occurs between RBP
protein J of phage and LamB of the host E.coli
• phage targets new receptor, OmpF of E.coli B
• When expression of LamB of host is reduced due
• when a mutated form of a host receptor is
expressed, phages can evolve to recognize the
altered receptor structure.
Phage strategies to access
a. Evolving a new RBP
b. Gaining access to masked receptors
c. Stochastic expression of RBPs
Phage strategies to access host
Phages can adapt to receptor changes. Phage receptor-binding proteins (RBPs)
recognize specific receptors on the host cell surface, but if the cognate receptor is
modified through mutation or replaced by a different molecule, then the phage is
unable to adsorb to the host. To infect this receptor-modified host, the phage can
evolve to target a new receptor, by acquiring mutations in the genes encoding the RBP
or tail fibres. For example, mutations in the gene encoding protein J of coliphage λ
enables this RBP to recognize a new receptor, OmpF, in addition to the cognate
The expression of surface molecules (for example, capsule or
exopolysaccharide (EPS)) at the receptor site can limit or
prevent phage access. If the phage lacks the enzymes required
to degrade the capsule or biofilm matrix, it cannot access the
receptor. However, if the phage possesses a depolymerase, it can
degrade these substances to unmask the receptor.
Some bacteria express phage receptors in a stochastic manner, either through
phase variation or through physiological regulation (such as in response to
growth phase). Phages can modify their RBPs in a manner that allows them to
interact with a surface component that is expressed by the host at that time.
This can be achieved by mutations in the gene encoding major tropism
determinant (Mtd) for the Bordetella spp. phages, by proteolytic cleavage of tail
fibres for Lactococcus lactis phages TP901-1 and Tuc2009 or by duplication of a
His box element in the coliphage T4 tail proteins.
Passive and active strategies to avoid
Some phages have few restriction sites in their
genome, or these sites are too far apart to be
recognized by the host restriction endonuclease
(REase), thus preventing targeting.
The phage genome can be modified by the host
methyltransferase (MTase). The modified phage is able to
multiply, and the newly synthesized viral DNA will be
protected against this specific REase when it infects other
host cells containing the same restriction–modification
system. Alternatively, the phage can encode its own
MTase, and if the modification generated by this enzyme
is compatible with the host REase, the phage DNA is
protected at each replication cycle.
A phage can co-inject proteins such as DarA and
DarB (of phage P1) with its genome to bind
directly to the phage DNA and mask restriction
A phage protein (such as Ocr of phage T7) mimics
the target DNA and sequesters the restriction
enzyme. Ocr binds to both the MTase and the REase
of the type I restriction–modification system EcoKI
and inhibits its activity.
A phage protein such as Ral of phage λ can activate
the activity of the MTase and thereby accelerate
protection of the phage DNA. The peptide Stp of
phage T4 can also inhibit restriction by direct
perturbation of the REase –MTase complex.
These are the part of bacterial immune system which detects and
recognize the foreign DNA and cleaves it.
1. The CRISPR (clustered regularly interspaced short palindromic
repeats) loci and
2. Cas (CRISPR-associated) proteins can
target and cleave invading DNA in a sequence-specific manner.
Spacer=The direct repeats in a CRISPR locus are separated by short
stretches of non-repetitive DNA called spacers that are typically
derived from invading plasmid or phage DNA.
Protospacers = The nucleotide sequence of the spacer must be similar
to a region in the phage genome called a protospacer in order to
recognize and subsequently block phage replication.
CRISPR–Cas systems function in three
1) adaptation or immunization (involving the
acquisition of spacers
2) biogenesis of CRISPR RNA (crRNA; encoded
by the repeat–spacer regions)
3) interference (cleavage of invading nucleic
The direct repeats of the CRISPR locus are separated by short stretches of non-
repetitive DNA called spacers, which are acquired from the invading DNA of plasmids
or viruses in a process known as adaptation.
2. biogenesis of CRISPR RNA
The CRISPR locus is transcribed as a long primary pre-crRNA transcript, which is
processed to produce a collection of short crRNAs (a process referred to as
biogenesis of crRNA. Each crRNA contains segments of a repeat and a full spacer and,
in conjunction with a set of Cas proteins, forms the core of CRISPR–Cas complexes.
These complexes act as a surveillance system and provide immunity against ensuing
infections by phages or plasmids encoding DNA complementary to the crRNA.
On recognition of a matching target sequence, the plasmid or viral DNA is cleaved in
a sequence-specific manner (known as interference). The nucleotide sequence of the
spacer must be identical to a region of the viral genome or plasmid (known as the
protospacer) for the CRISPR–Cas complex to block replication of the foreign element.
Phage strategies to by-pass
• Mutations in the phage protospacers or in the protospacer-
adjacent motif (PAM) render the phage insensitive to the
interference step of the CRISPR–Cas system, owing to the
requirement for complementarity between the CRISPR RNA
(crRNA) and the target DNA.
• The anti-CRISPR system of Pseudomonas aeruginosa
lysogens. The phage-encoded anti-CRISPR protein blocks
the interference step by preventing the formation or
blocking the action of the CRISPR–Cas complexes.
The CRISPR–Cas system of Vibrio cholerae phages. After entry of the phage
genome into the cell, the viral crRNAs and CRISPR–Cas complexes are
expressed and target an uncharacterized antiphage system of the V. cholerae
host; the latter system is contained within a locus resembling a phage-
inducible chromosomal island (PICI), referred to as a PICI-like element (PLE).
The spacers in the phage CRISPR locus are complementary to PLE sequences,
and the CRISPR machinery is then able to specifically target this genetic
element and inactivate it.
Phage strategies to by-pass toxin–
During normal bacterial
growth, the antitoxin
preventing bacterial cell
During phage infection, an
imbalance in the toxin–antitoxin
ratio or inactivation of the
antitoxin results in liberation of
the toxin, which is free to act on
its target and inhibit bacterial
growth. This growth inhibition
also leads to the abortion of
When certain genes in Lactococcus
spp. phages are mutated, the phages
can by-pass abortive-infection (Abi)
systems. For example, related
Lactococcus spp. phages can by-pass
the AbiQ mechanism through
mutations in genes involved in
Some phages encode a molecule (for
example, Dmd of coliphage T4) that
functionally replaces the bacterial
antitoxin, thereby counteracting
toxin activity and avoiding host
death. Phage ϕTE of Pectobacterium
atrosepticum produces a pseudo-
antitoxin RNA or hijacks the native
antitoxin ToxI to neutralize the toxin
ToxN during phage infection.