scholarly journals Erratum: Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

2016 ◽  
Vol 15 (2) ◽  
pp. 143-143
Author(s):  
David Brown
Keyword(s):  
Antibiotic Resistance ◽  
Repurposed Drugs ◽  
Antibiotic Discovery

scholarly journals Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

2019 ◽  
Vol 20 (6) ◽  
pp. 1255 ◽  
Author(s):  
Ana Monserrat-Martinez ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Rational Design ◽  
Disease Onset ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

scholarly journals Over-activation of a nonessential bacterial protease DegP as an antibiotic strategy

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hyunjin Cho ◽  
Yuri Choi ◽  
Kyungjin Min ◽  
Jung Bae Son ◽  
Hyojin Park ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Binding Sites ◽  
Antibiotic Development ◽  
Essential Proteins ◽  
Bacterial Protease ◽  
Novel Targets ◽  
Essential Enzyme ◽  
Substrate Binding Sites ◽  
Antibiotic Discovery

AbstractRising antibiotic resistance urgently begs for novel targets and strategies for antibiotic discovery. Here, we report that over-activation of the periplasmic DegP protease, a member of the highly conserved HtrA family, can be a viable strategy for antibiotic development. We demonstrate that tripodal peptidyl compounds that mimic DegP-activating lipoprotein variants allosterically activate DegP and inhibit the growth of an Escherichia coli strain with a permeable outer membrane in a DegP-dependent fashion. Interestingly, these compounds inhibit bacterial growth at a temperature at which DegP is not essential for cell viability, mainly by over-proteolysis of newly synthesized proteins. Co-crystal structures show that the peptidyl arms of the compounds bind to the substrate-binding sites of DegP. Overall, our results represent an intriguing example of killing bacteria by activating a non-essential enzyme, and thus expand the scope of antibiotic targets beyond the traditional essential proteins or pathways.

scholarly journals Tiny Earth: A Big Idea for STEM Education and Antibiotic Discovery

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanda Hurley ◽  
Marc G. Chevrette ◽  
Deepa D. Acharya ◽  
Gabriel L. Lozano ◽  
Manuel Garavito ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Stem Education ◽  
Undergraduate Research ◽  
Bacterial Pathogens ◽  
The World ◽  
Stem Workforce ◽  
Antibiotic Discovery

ABSTRACT The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

scholarly journals Tiny Earth: A Big Idea for STEM Education and Antibiotic Discovery

2020 ◽  
Author(s):  
Amanda Hurley ◽  
Marc G. Chevrette ◽  
Deepa D. Acharya ◽  
Gabriel L. Lozano ◽  
Manuel Garavito ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Stem Education ◽  
Undergraduate Research ◽  
Bacterial Pathogens ◽  
The World ◽  
Stem Workforce ◽  
Antibiotic Discovery

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

scholarly journals Application of iChip to Grow “Uncultivable” Microorganisms and its Impact on Antibiotic Discovery

2015 ◽  
Vol 18 (3) ◽  
pp. 303 ◽  
Author(s):  
Rinzhin T. Sherpa ◽  
Caretta J. Reese ◽  
Hamidreza Montazeri Aliabadi
Keyword(s):  
Antimicrobial Activity ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Modern Medicine ◽  
Natural Phenomenon ◽  
Significant Progress ◽  
Cultivation Method ◽  
New Antibiotics ◽  
Antibiotic Discovery

Antibiotics have revolutionized modern medicine, allowing significant progress in healthcare and improvement in life expectancy. Development of antibiotic resistance by pathogenic bacteria is a natural phenomenon; however, the rate of antibiotic resistance emergence is increasing at an alarming rate, due to indiscriminate use of antibiotics in healthcare, agriculture and even everyday products. Traditionally, antibiotic discovery has been conducted by screening extracts of microorganisms for antimicrobial activity. However, this conventional source has been over-used to such an extent that it poses the risk of “running out” of new antibiotics. Aiming to increase access to a greater diversity of microorganisms, a new cultivation method with an in situ approach called iChip has been designed. The iChip has already isolated many novel organisms, as well as Teixobactin, a novel antibiotic with significant potency against gram-positive bacteria.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Kristofer Wollein Waldetoft ◽  
James Gurney ◽  
Joseph Lachance ◽  
Paul A. Hoskisson ◽  
Sam P. Brown
Keyword(s):  
Antibiotic Resistance ◽  
Experimental Evolution ◽  
Rational Design ◽  
Antibiotic Production ◽  
Molecular Targets ◽  
Resistance Mechanisms ◽  
Mechanisms Of Resistance ◽  
Complex Functions ◽  
Evolution Of Resistance ◽  
Antibiotic Discovery

ABSTRACT To avoid an antibiotic resistance crisis, we need to develop antibiotics at a pace that matches the rate of evolution of resistance. However, the complex functions performed by antibiotics—combining, e.g., penetration of membranes, counteraction of resistance mechanisms, and interaction with molecular targets—have proven hard to achieve with current methods for drug development, including target-based screening and rational design. Here, we argue that we can meet the evolution of resistance in the clinic with evolution of antibiotics in the laboratory. On the basis of the results of experimental evolution studies of microbes in general and antibiotic production in Actinobacteria in particular, we propose methodology for evolving antibiotics to circumvent mechanisms of resistance. This exploits the ability of evolution to find solutions to complex problems without a need for design. We review evolutionary theory critical to this approach and argue that it is feasible and has important advantages over current methods for antibiotic discovery.

scholarly journals Laser-Irradiated Chlorpromazine as a Potent Anti-Biofilm Agent for Coating of Biomedical Devices

Coatings ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1230
Author(s):  
Simona Nistorescu ◽  
Gratiela Gradisteanu Pircalabioru ◽  
Ana-Maria Udrea ◽  
Agota Simon ◽  
Mihail Lucian Pascu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antibiotic Resistance ◽  
Laser Radiation ◽  
Laser Exposure ◽  
Health Crisis ◽  
Bactericidal Effects ◽  
Biological Target ◽  
Combined Action ◽  
Repurposed Drugs ◽  
Visible Activity

Nowadays, antibiotic resistance has become increasingly common, triggering a global health crisis, immediately needing alternative, including repurposed drugs with potent bactericidal effects. We demonstrated that chlorpromazine aqueous solutions exposed to laser radiation exhibited visible activity against various microorganisms. The aim of this study was to investigate the quantitative antimicrobial activity of chlorpromazine in non-irradiated and 4-h laser irradiated form. Also, we examined the effect of both solutions impregnated on a cotton patch, cannula, and urinary catheter against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa and Escherichia coli. In all experimental versions, the chlorpromazine antimicrobial activity was enhanced by laser exposure. Besides the experimental results, the in silico analyses using molecular docking proved that the improved antimicrobial activity of the irradiated compound was a result of the combined action of the photoproducts on the biological target (s). Our results show that laser radiation could alter the molecular structure of various drugs and their effects, proving to be a promising strategy to halt antibiotic resistance, by repurposing current medicines for new antimicrobial strategies, thereby decreasing the costs and time for the development of more efficient drugs.

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