Novel therapeutics for bacterial infections

2017 ◽  
Vol 1 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Peter W. Taylor
Keyword(s):  
Antibiotic Resistance ◽  
Drug Discovery ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Novel Therapeutics ◽  
The Past ◽  
Encoded Proteins ◽  
New Antibiotics ◽  
Marked Decline

The relentless increase in antibiotic resistance among all major groups of bacterial pathogens shows no sign of abating. The situation is exacerbated by a marked decline in the number of new antibiotics entering the marketplace. It is essential that new ways to treat severe bacterial infections are investigated before the antibiotic well runs dry. This review covers many promising approaches, some novel and some based on old ideas that were not considered viable when clinicians were able to exploit a wide palette of cheap and effective antibacterial chemotherapeutics. These approaches include the use of photosensitive dyes, bacteriophage and phage-encoded proteins, and agents that compromise virulence and antibiotic-resistance machineries. I also make a case for continuing in some form with tried and trusted platforms for drug discovery that served society well in the past.

scholarly journals Antimicrobial Activity of Biosynthesized Silver Nanoparticles Compared to Standard Antibiotics Used in ORL Infections

2019 ◽  
Vol 70 (7) ◽  
pp. 2571-2573
Author(s):  
Alina Andreea Tischer (Tucuina) ◽  
Delia Berceanu Vaduva ◽  
Nicolae Balica ◽  
Alina Heghes ◽  
Adelina Cheveresan ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Silver Nanoparticles ◽  
Antibiotic Resistance ◽  
Adverse Effects ◽  
Infectious Diseases ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
New Antibiotics ◽  
Recorded Data

In recent years, bacterial infections in hospitals have grown particularly due to the development of antibiotic resistance. Recent research targets the discovery of new antibiotics that exhibit broad spectrum of action without adverse effects or minimizing adverse effects. In this study, the activity of biosynthesized silver nanoparticles against three bacteria commonly found in infectious diseases in the ORL sphere was evaluated. The recorded data revealed an activity comparable to that of the standard antibiotics used in these types of infections, with the observation that the activity of the nanoparticles could also be observed in the particular cases of antibiotic resistance.

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.

The requirements at the C-3 position of alkylquinolones for signalling in Pseudomonas aeruginosa

2017 ◽  
Vol 15 (2) ◽  
pp. 306-310 ◽  
Author(s):  
Rachel Shanahan ◽  
F. Jerry Reen ◽  
Rafael Cano ◽  
Fergal O'Gara ◽  
Gerard P. McGlacken
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Innovative Strategies ◽  
Bacterial Antibiotic Resistance ◽  
New Antibiotics ◽  
Perfect Storm

The ‘perfect storm’ of increasing bacterial antibiotic resistance and a decline in the discovery of new antibiotics, has made it necessary to search for new and innovative strategies to treat bacterial infections.

scholarly journals Can Bees Help us Find New Antibiotics?

2021 ◽  
Vol 9 ◽  
Author(s):  
Kirstie A. Goggin ◽  
Les Baillie
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Antibiotic Activity ◽  
Antibacterial Compounds ◽  
Improper Use ◽  
New Antibiotics ◽  
University Buildings

Antibiotics are very important for treating bacterial infections in humans, pets, and livestock. However, improper use of antibiotics has resulted in antibiotic resistance, making it difficult to treat some infections. There is an urgent need to discover new antibiotics, but how do we find them? The answer potentially lies with bees and the honey they produce. Bees who feed on unique plants produce honey with high levels of antibiotic activity, due to the presence of antibacterial compounds in the nectar that the bees collect to make honey. In addition to nectar, the bees also collect pollen, which contains a sample of each visited plant’s unique DNA. By studying this DNA, we have identified plants that are sources of the antibacterial compounds found in honey. We are now working to develop new antibiotics from this honey, and we have installed beehives on university buildings to create our own super honey.

scholarly journals Upregulation of gluconeogenesis leads to increased tolerance to antibiotics targeting the MreB elongosome in E. coli

2020 ◽  
Author(s):  
Brody Barton ◽  
Addison Grinnell ◽  
Randy M. Morgenstein
Keyword(s):  
Antibiotic Resistance ◽  
Minimal Inhibitory Concentration ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Resistance Mechanism ◽  
Tca Cycle ◽  
Resistant Bacteria ◽  
Antibiotic Development ◽  
New Antibiotics ◽  
Global Threat

AbstractAntibiotic resistant bacteria are a global threat to human health. One way to combat the rise of antibiotic resistance is to make new antibiotics that target previously ignored proteins. The bacterial actin homolog, MreB, is highly conserved among rod-shaped bacteria and essential for growth, making MreB a good focus for antibiotic targeting. Therefore, it is imperative to understand mechanisms that can give rise to resistance to MreB targeting drugs. Using the MreB targeting drug, A22, we show that changes to central metabolism through deletion of TCA cycle genes, leads to the upregulation of gluconeogenesis resulting in cells with an increased minimal inhibitory concentration to A22. This phenotype can be recapitulated through the addition of glucose to the media. Finally, we show that this increase in minimal inhibitory concentration is not specific to A22 but can be seen in other cell wall targeting antibiotics, such as mecillinam.ImportanceThe spread of antibiotic resistance has made bacterial infections harder to treat. Finding new targets for antibiotic development is critical to overcoming the variety of resistance mechanism that are already crippling our ability to treat infections with current antibiotics. The bacterial actin homolog MreB is a good target for new antibiotic development because it is essential for growth and highly conserved among rod-shaped pathogens. The significance of this research is in understanding the mechanisms cells can develop toward the inhibition of MreB to better understand how to make MreB targeting antibiotics in the future.

Drug repurposing for antivirulence therapy against opportunistic bacterial pathogens

2017 ◽  
Vol 1 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Giordano Rampioni ◽  
Paolo Visca ◽  
Livia Leoni ◽  
Francesco Imperi
Keyword(s):  
Bacterial Infections ◽  
Drug Research ◽  
Bacterial Pathogens ◽  
Drug Repurposing ◽  
Health Concern ◽  
Challenges And Opportunities ◽  
New Antibiotics ◽  
Speed Up ◽  
Pathogenic Process

Antibiotic resistance is a serious public health concern at the global level. Available antibiotics have saved millions of lives, but are progressively losing their efficacy against many bacterial pathogens, and very few new antibiotics are being developed by the pharmaceutical industry. Over the last few decades, progress in understanding the pathogenic process of bacterial infections has led researchers to focus on bacterial virulence factors as potential targets for ‘antivirulence' drugs, i.e. compounds which inhibit the ability of bacteria to cause damage to the host, as opposed to inhibition of bacterial growth which is typical of antibiotics. Hundreds of virulence inhibitors have been examined to date in vitro and/or in animal models, but only a few were entered into clinical trials and none were approved, thus hindering the clinical validation of antivirulence therapy. To breathe new life into antivirulence research and speed-up its transfer to the clinic, antivirulence activities have also been sought in drugs already approved for different therapeutic purposes in humans. If effective, these drugs could be repositioned for antivirulence therapy and have an easier and faster transfer to the clinic. In this work we summarize the approaches which have led to the identification of repurposing candidates with antivirulence activities, and discuss the challenges and opportunities related to antivirulence therapy and drug repurposing. While this approach undoubtedly holds promise for boosting antivirulence drug research, some important issues remain to be addressed in order to make antivirulence drugs viable alternatives to traditional antibacterials.

scholarly journals Applications of Raman Spectroscopy in Bacterial Infections: Principles, Advantages, and Shortcomings

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Wang ◽  
Wei Liu ◽  
Jia-Wei Tang ◽  
Jun-Jiao Wang ◽  
Qing-Hua Liu ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Antibiotic Resistance ◽  
Infectious Diseases ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Basic Research ◽  
Label Free ◽  
Clinical Implementation ◽  
Label Free Detection

Infectious diseases caused by bacterial pathogens are important public issues. In addition, due to the overuse of antibiotics, many multidrug-resistant bacterial pathogens have been widely encountered in clinical settings. Thus, the fast identification of bacteria pathogens and profiling of antibiotic resistance could greatly facilitate the precise treatment strategy of infectious diseases. So far, many conventional and molecular methods, both manual or automatized, have been developed for in vitro diagnostics, which have been proven to be accurate, reliable, and time efficient. Although Raman spectroscopy (RS) is an established technique in various fields such as geochemistry and material science, it is still considered as an emerging tool in research and diagnosis of infectious diseases. Based on current studies, it is too early to claim that RS may provide practical guidelines for microbiologists and clinicians because there is still a gap between basic research and clinical implementation. However, due to the promising prospects of label-free detection and noninvasive identification of bacterial infections and antibiotic resistance in several single steps, it is necessary to have an overview of the technique in terms of its strong points and shortcomings. Thus, in this review, we went through recent studies of RS in the field of infectious diseases, highlighting the application potentials of the technique and also current challenges that prevent its real-world applications.

scholarly journals Targeting virulence: salmochelin modification tunes the antibacterial activity spectrum of β-lactams for pathogen-selective killing of Escherichia coli

2015 ◽  
Vol 6 (8) ◽  
pp. 4458-4471 ◽  
Author(s):  
Phoom Chairatana ◽  
Tengfei Zheng ◽  
Elizabeth M. Nolan
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
New Antibiotics ◽  
Activity Spectrum

New antibiotics are required to treat bacterial infections and counteract the emergence of antibiotic resistance.

scholarly journals Translational control of antibiotic resistance

Open Biology ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 190051 ◽  
Author(s):  
Anne Witzky ◽  
Rodney Tollerson ◽  
Michael Ibba
Keyword(s):  
Antibiotic Resistance ◽  
Drug Discovery ◽  
Translational Control ◽  
Treatment Options ◽  
Mechanisms Of Resistance ◽  
Translation Elongation ◽  
The Past ◽  
New Treatment ◽  
Bacterial Translation ◽  
Ribosomal Protection

Many antibiotics available in the clinic today directly inhibit bacterial translation. Despite the past success of such drugs, their efficacy is diminishing with the spread of antibiotic resistance. Through the use of ribosomal modifications, ribosomal protection proteins, translation elongation factors and mistranslation, many pathogens are able to establish resistance to common therapeutics. However, current efforts in drug discovery are focused on overcoming these obstacles through the modification or discovery of new treatment options. Here, we provide an overview for common mechanisms of resistance to translation-targeting drugs and summarize several important breakthroughs in recent drug development.

scholarly journals Exceptions to the rule: Why does resistance evolution not undermine antibiotic therapy in all bacterial infections?

2021 ◽  
Author(s):  
Amrita Bhattacharya ◽  
Anton Aluquin ◽  
David A Kennedy
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Human Microbiome ◽  
Systematic Analysis ◽  
Resistance Evolution ◽  
Wide Range ◽  
Public Health Challenges

Antibiotic resistance poses one of the greatest public health challenges of the 21st century. Yet not all pathogens are equally affected by resistance evolution. Why? Here we examine what underlies variation in antibiotic resistance across human bacterial pathogens and the drugs used to treat them. We document the observed prevalence of antibiotic resistance for ′pathogen x drug′ combinations across 57 different human bacterial pathogens and 53 antibiotics from 15 drug classes used to treat them. Using AIC-based model selection we analyze 14 different traits of bacteria and antibiotics that are believed to be important in resistance evolution. Using these data, we identify the traits that best explain observed variation in resistance evolution. Our results show that nosocomial pathogens and indirectly transmitted pathogens are significantly associated with increased prevalence of resistance whereas zoonotic pathogens, specifically those with wild animal reservoirs, are associated with reduced prevalence of resistance. We found partial support for associations between drug resistance and gram classification, human microbiome reservoirs, horizontal gene transfer, and documented human-to human transfer. Global drug use, time since drug discovery, mechanism of drug action, and environmental reservoirs did not emerge as statistically robust predictors of drug resistance in our analyses. To the best of our knowledge this work is the first systematic analysis of resistance across such a wide range of human bacterial pathogens, encompassing the vast majority of common bacterial pathogens. Insights from our study may help guide public health policies and future studies on resistance control.

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