For a long time, antibiotics have been ‘magical weapons’ to
combat pathogenic microbes. The success of antibiotics is
now greatly threatened by resistance to antibiotics and many
scientists have already talked about the coming of the postantibiotic
era. This special issue is prepared to understand
recent research findings and new concepts about antibiotic
resistance. Above all, this special issue explores mechanisms
for the generation, selection, and spread of antibiotic resistance,
and gives insight into what to target to prevent the development
of antibiotic resistance. Just as antibiotics came
from the concept of “magic bullet”, a breakthrough will come
from a new concept based on a profound understanding of
antibiotic resistance.
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Tripartite efflux pumps and the type I secretion system of
Gram-negative bacteria are large protein complexes that span
the entire cell envelope. These complexes expel antibiotics and
other toxic substances or transport protein toxins from bacterial
cells. Elucidating the binary and ternary complex structures
at an atomic resolution are crucial to understanding the
assembly and working mechanism. Recent advances in cryoelectron
microscopy along with the construction of chimeric
proteins drastically shifted the assembly models. In this review,
we describe the current assembly models from a historical
perspective and emphasize the common assembly mechanism
for the assembly of diverse tripartite pumps and type
I secretion systems.
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Antibiotic resistance is a global concern in public health.
Antibiotic-resistant clones can spread nationally, internationally,
and globally. This review considers representative
antibiotic-resistant Gram-negative bacterial clones–CTX-M-
15-producing ST131 in Escherichia coli, extended-spectrum
β-lactamase-producing ST11 and KPC-producing ST258 in
Klebsiella pneumoniae, IMP-6-producing, carbapenem-resistant
ST235 in Pseudomonas aeruginosa, and OXA-23-
producing global clone 2 in Acinetobacter baumannii–that
have disseminated worldwide, including in Korea. The findings
highlight the urgency for systematic monitoring and
international cooperation to suppress the emergence and
propagation of antibiotic resistance.
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Oxidative stress arises from an imbalance between the excessive
accumulation of reactive oxygen species (ROS) and
a cell’s capability to readily detoxify them. Although ROS are
spontaneously generated during the normal oxygen respiration
and metabolism, the ROS generation is usually augmented
by redox-cycling agents, membrane disrupters, and
bactericidal antibiotics, which contributes their antimicrobial
bioactivity. It is noted that all the bacteria deploy an arsenal
of inducible antioxidant defense systems to cope with the
devastating effect exerted by the oxidative stress: these systems
include the antioxidant effectors such as catalases and
the master regulators such as OxyR. The oxidative stress response
is not essential for normal growth, but critical to survive
the oxidative stress conditions that the bacterial pathogens
may encounter due to the host immune response and/or
the antibiotic treatment. Based on these, we here define the
ROS-inspired antibacterial strategies to enhance the oxidative
stress of ROS generation and/or to compromise the bacterial
response of ROS detoxification, by delineating the ROSgenerating
antimicrobials and the core concept of the bacterial
response against the oxidative stress.
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Since most bacterial cells are starving, they must enter a resting
stage. Persister is the term used for metabolically-dormant
cells that are not spores, and these cells arise from stress
such as that from antibiotics as well as that from starvation.
Because of their lack of metabolism, persister cells survive
exposure to multiple stresses without undergoing genetic
change; i.e., they have no inherited phenotype and behave as
wild-type cells once the stress is removed and nutrients are
presented. In contrast, mutations allow resistant bacteria to
grow in the presence of antibiotics and slow growth allows
tolerant cells to withstand higher concentrations of antibiotics;
hence, there are three closely-related phenotypes: persistent,
resistant, and tolerant. In addition, since dormancy
is so prevalent, persister cells must have a means for resuscitating
(since so many cells should obtain this resting state).
In this review, we focus on what is known about the formation
and resuscitation of persister cells.
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