10.1586/ERI.12.145 1 ISSN 1478-7210 © 2012 Expert Reviews Ltd www.expert-reviews.com
Review
Bacterial adherence, the binding of bacteria to
other cells or inanimate surfaces, is a key prop-
erty that allows bacteria to survive and flour-
ish. Bacteria have the ability to attach to sites in
microenvironments where growth is favorable,
both in ecological niches and in vivo, within a
host. This property has long been known, with
significant parallels established between infec-
tivity and adhesiveness [1] . That adherence is a
prerequisite for the subsequent development of
disease symptoms for the majority of enteric,
respiratory and oral infections [2] . As such, this
area is increasingly becoming a source to mine
for novel therapeutics in an attempt to prevent
and treat bacterial infectious diseases.
This will become progressively more impor-
tant, as antibiotic resistance continues to
increase. Among new methods to tackle infec-
tious diseases, anti-adhesion therapies hold par-
ticular advantages, as they do not directly cause
the death of bacteria, an important selective
pressure. Strains with mutations that thwart
anti-adhesion mechanisms will inevitably
develop; however, unlike antibiotics, which kill
or stop the growth of the susceptible bacteria,
nonresistant strains can continue to propagate
and be transmitted to new hosts. Any wild-
type strains would continue to compete with
resistant strains in untreated individuals, act-
ing to prevent wide propagation of resistance
(FIGURE 1) [3] .
Adherence and subsequent internaliza-
tion confer advantages to bacteria, facilitating
delivery of virulence factors and toxins, aiding
acquisition of vital nutrients and evasion of
both the host immune system and any antibiot-
ics. Adherence confers tissue tropism, allowing
specificity of the interaction between host and
pathogen to ensure bacteria take advantage of
the environment most appropriate to their physi-
ological and metabolic requirements. By block-
ing the interactions responsible for infectivity,
either by prevention or dissociation, the unat-
tached organisms can be eliminated by nonspe-
cific cleansing mechanisms of the host, halting
the development of an infection (FIGURE 2) . These
clearance mechanisms vary between different
regions of the body. They include the action of
mucocilary removal in the airway [4] and fal-
lopian tube, the flushing effect of urine in the
urinary tract and bladder producing shear force,
the shedding of upper epithelial cell layers and
the lining of tracts and tissue with antibodies,
all of which inhibit bacterial attachment. These
help to prevent bacterial adherence or dislodge
weakly bound bacteria for removal from the
host. Alternatively, weakening the tight associa-
tion allows easier elimination of the pathogen by
the immune system.
Anti-adhesion therapies might be deployed
in several ways. Treatment might be given as
prophylaxis when infection is probable, such as
Daniel Cozens
1
and
Robert C Read*
2
1
Department of Infection and Immunity,
K Floor, Royal Hallamshire Hospital,
Sheffield School of Medicine and
Biomedical Science, University of
Sheffield, Sheffield, S10 3JF, UK
2
Department of Clinical and
Experimental Sciences, University of
Southampton, Southampton General
Hosptal, Tremona Rd, Southampton,
SO16 6YD, UK
*Author for correspondence:
Tel.: +44 114 271 2237
r.c.read@soton.ac.uk
Anti-adhesion therapies for bacterial infections offer an alternative to antibiotics, in which
bacteria are not killed but are prevented from causing harm to a host by inhibiting adherence
to host cells and tissues, a prerequisite for the majority of infectious diseases. The mechanisms
of these potential therapeutic agents include inhibition of adhesins and their host receptors,
vaccination with adhesins or analogs, use of probiotics and dietary supplements that interfere
with receptor–adhesin interactions, subminimal inhibitory concentrations of antibiotics and
manipulation of hydrophobic interactions.Once developed, these drugs will contribute to the
arsenal for fighting infectious disease in the future, potentially subverting antibiotic resistance.
Anti-adhesion methods
as novel therapeutics for
bacterial infections
Expert Rev. Anti Infect. Ther. 10(12), 00–00 (2012)
KEYWORDS:adhesins•anti-adhesiontherapy•antibioticresistance•bacterialadherence
Author Proof