The
Recalcitrance
of
pathogens
to
traditional
antibiotics
has
made
treating
and
eradicating
bacterial
infections
more
difficult.
In
this
regard,
developing
new
antimicrobial
agents
combat
antibiotic-resistant
strains
become
a
top
priority.
Antimicrobial
peptides
(AMPs),
ubiquitous
class
naturally
occurring
compounds
with
broad-spectrum
anti-pathogen
activity,
hold
significant
promise
as
one
the
most
effective
solutions
current
resistance
(AMR)
crisis.
Several
AMPs
have
been
identified
evaluated
for
their
therapeutic
application,
many
already
in
drug
development
pipeline.
Their
distinct
properties,
such
high
target
specificity,
potency,
ability
bypass
microbial
mechanisms,
make
them
promising
alternative
antibiotics.
Nonetheless,
several
challenges,
toxicity,
lability
proteolytic
degradation,
low
stability,
poor
pharmacokinetics,
production
costs,
continue
hamper
clinical
applicability.
Therefore,
much
recent
research
focused
on
optimizing
peptides'
properties
improve
performance.
By
understanding
physiochemical
AMPs,
amphipathicity,
hydrophobicity,
structural
conformation,
amino
acid
distribution,
composition,
that
correspond
researchers
can
design
desired
improved
review,
we
highlight
some
key
strategies,
rational
de
novo
design,
used
optimize
performance
AMPs.
We
also
discuss
how
evolution
predictive
computational
tools
technologies
utilize
artificial
intelligence
machine
learning
are
increasingly
being
synthesize
lead
candidates
efficacy.
ACS Omega,
Год журнала:
2023,
Номер
8(12), С. 10757 - 10783
Опубликована: Март 14, 2023
The
problem
of
antibiotic
resistance
is
on
the
rise,
with
multidrug-resistant
strains
emerging
even
to
last
resort
antibiotics.
drug
discovery
process
often
stalled
by
stringent
cut-offs
required
for
effective
design.
In
such
a
scenario,
it
prudent
delve
into
varying
mechanisms
existing
antibiotics
and
target
them
improve
efficacy.
Nonantibiotic
compounds
called
adjuvants
which
bacterial
can
be
used
in
combination
obsolete
drugs
an
improved
therapeutic
regime.
field
"antibiotic
adjuvants"
has
gained
significant
traction
recent
years
where
other
than
β-lactamase
inhibition
have
been
explored.
This
review
discusses
multitude
acquired
inherent
employed
bacteria
resist
action.
major
focus
this
how
these
use
adjuvants.
Different
types
direct
acting
indirect
breakers
are
discussed
including
enzyme
inhibitors,
efflux
pump
inhibitors
teichoic
acid
synthesis,
cellular
processes.
multifaceted
class
membrane-targeting
poly
pharmacological
effects
potential
host
immune-modulating
also
reviewed.
We
conclude
providing
insights
about
challenges
preventing
clinical
translation
different
classes
adjuvants,
especially
membrane-perturbing
compounds,
framework
possible
directions
pursued
fill
gap.
Antibiotic–adjuvant
combinatorial
therapy
indeed
immense
as
upcoming
orthogonal
strategy
conventional
discovery.
Microorganisms,
Год журнала:
2024,
Номер
12(7), С. 1259 - 1259
Опубликована: Июнь 21, 2024
Antimicrobial
resistance
(AMR)
poses
a
serious
global
health
concern,
resulting
in
significant
number
of
deaths
annually
due
to
infections
that
are
resistant
treatment.
Amidst
this
crisis,
antimicrobial
peptides
(AMPs)
have
emerged
as
promising
alternatives
conventional
antibiotics
(ATBs).
These
cationic
peptides,
naturally
produced
by
all
kingdoms
life,
play
crucial
role
the
innate
immune
system
multicellular
organisms
and
bacterial
interspecies
competition
exhibiting
broad-spectrum
activity
against
bacteria,
fungi,
viruses,
parasites.
AMPs
target
pathogens
through
multiple
mechanisms,
most
importantly
disrupting
their
membranes,
leading
cell
lysis.
However,
host
has
slow
co-evolutionary
process
between
microorganisms
hosts.
Alarmingly,
development
last-resort
treatment
MDR
infections,
such
colistin,
is
attributed
misuse
peptide
high
rate
horizontal
genetic
transfer
corresponding
genes.
AMP-resistant
bacteria
employ
diverse
including
but
not
limited
proteolytic
degradation,
extracellular
trapping
inactivation,
active
efflux,
well
complex
modifications
wall
membrane
structures.
This
review
comprehensively
examines
constitutive
inducible
molecular
mechanisms
supported
experimental
evidence
described
date
pathogens.
We
also
explore
specificity
these
toward
structurally
broaden
enhance
potential
developing
applying
them
therapeutics
for
bacteria.
Additionally,
we
provide
insights
into
significance
AMP
within
context
host-pathogen
interactions.
International Journal of Molecular Sciences,
Год журнала:
2016,
Номер
17(5), С. 701 - 701
Опубликована: Май 11, 2016
Antimicrobial
peptides
(AMPs)
are
an
interesting
class
of
antibiotics
characterized
by
their
unique
antibiotic
activity
and
lower
propensity
for
developing
resistance
compared
to
common
antibiotics.
They
belong
the
membrane-active
usually
act
selectively
against
bacteria,
fungi
protozoans.
AMPs,
but
also
peptide
conjugates
containing
have
come
more
into
focus
research
during
last
few
years.
Within
this
article,
recent
work
on
AMP
is
reviewed.
Different
aspects
will
be
highlighted
as
a
combination
AMPs
with
or
organometallic
compounds
aiming
increase
antibacterial
target
selectivity,
conjugation
photosensitizers
improving
photodynamic
therapy
(PDT)
attachment
particles,
name
only
few.
Owing
enormous
resonance
antimicrobial
in
literature
so
far,
topic
seems
very
attractive
different
scientific
fields,
like
medicine,
biology,
biochemistry
chemistry.
Antibiotics,
Год журнала:
2020,
Номер
9(1), С. 17 - 17
Опубликована: Янв. 3, 2020
Daptomycin
is
a
cyclic
lipopeptide
antibiotic,
which
was
discovered
in
1987
and
entered
the
market
2003.
To
date,
it
serves
as
last
resort
antibiotic
to
treat
complicated
skin
infections,
bacteremia,
right-sided
endocarditis
caused
by
Gram-positive
pathogens,
most
prominently
methicillin-resistant
Staphylococcus
aureus.
representative
of
novel
class
that
introduced
clinic.
It
also
one
few
membrane-active
compounds
can
be
applied
systemically.
While
antibiotics
have
long
been
limited
topical
applications
were
generally
excluded
from
systemic
drug
development,
they
promise
slower
resistance
development
than
many
classical
drugs
target
single
proteins.
The
success
daptomycin
together
with
emergence
more
multi-resistant
superbugs
attracted
renewed
interest
this
compound
class.
Studying
pioneering
might
help
pave
way
for
future
membrane-targeting
antibiotics.
However,
30
years
after
its
discovery,
exact
mechanism
action
still
debated.
In
particular,
there
prominent
discrepancy
between
vivo
vitro
studies.
review,
we
discuss
current
knowledge
on
against
bacteria
try
offer
explanations
these
conflicting
observations.
Future Medicinal Chemistry,
Год журнала:
2016,
Номер
8(12), С. 1413 - 1433
Опубликована: Авг. 1, 2016
In
recent
years,
the
increase
of
invasive
fungal
infections
and
emergence
antifungal
resistance
stressed
need
for
new
drugs.
Peptides
have
shown
to
be
good
candidates
development
alternative
antimicrobial
agents
through
high-throughput
screening,
subsequent
optimization
according
a
rational
approach.
This
review
presents
brief
overview
on
natural
peptides
different
sources
(animals,
plants,
micro-organisms),
peptide
fragments
derived
by
proteolytic
cleavage
precursor
physiological
proteins
(cryptides),
synthetic
unnatural
derivatives.
Antifungal
are
schematically
reported
based
their
structure,
spectrum
effects.
Natural
or
modified
derivatives
may
represent
basis
compounds
active
against
infections.
