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 Antibiotics in Food Chain: The Consequences for Antibiotic Resistance

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 688
Author(s):  
Shashi B. Kumar ◽  
Shanvanth R. Arnipalli ◽  
Ouliana Ziouzenkova
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Food Chain ◽  
Bacterial Infections ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Alternative Strategies ◽  
Antibiotic Resistant ◽  
Continuous Use

Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.

scholarly journals Antibiotic Resistance of Gram-Negative Bacteria from Wild Captured Loggerhead Sea Turtles

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 162 ◽  
Author(s):  
Monica Francesca Blasi ◽  
Luciana Migliore ◽  
Daniela Mattei ◽  
Alice Rotini ◽  
Maria Cristina Thaller ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Sea Turtles ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Marine Animals ◽  
Loggerhead Sea Turtles ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Marine Habitats ◽  
Resistant Strains

Sea turtles have been proposed as health indicators of marine habitats and carriers of antibiotic-resistant bacterial strains, for their longevity and migratory lifestyle. Up to now, a few studies evaluated the antibacterial resistant flora of Mediterranean loggerhead sea turtles (Caretta caretta) and most of them were carried out on stranded or recovered animals. In this study, the isolation and the antibiotic resistance profile of 90 Gram negative bacteria from cloacal swabs of 33 Mediterranean wild captured loggerhead sea turtles are described. Among sea turtles found in their foraging sites, 23 were in good health and 10 needed recovery for different health problems (hereafter named weak). Isolated cloacal bacteria belonged mainly to Enterobacteriaceae (59%), Shewanellaceae (31%) and Vibrionaceae families (5%). Although slight differences in the bacterial composition, healthy and weak sea turtles shared antibiotic-resistant strains. In total, 74 strains were endowed with one or multi resistance (up to five different drugs) phenotypes, mainly towards ampicillin (~70%) or sulfamethoxazole/trimethoprim (more than 30%). Hence, our results confirmed the presence of antibiotic-resistant strains also in healthy marine animals and the role of the loggerhead sea turtles in spreading antibiotic-resistant bacteria.

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.

scholarly journals Incidence of enterococci resistant to clinically relevant antibiotics in environmental waters and in reclaimed waters used for irrigation

2020 ◽  
Vol 18 (6) ◽  
pp. 911-924
Author(s):  
Silvia Monteiro ◽  
Ricardo Santos
Keyword(s):  
Antibiotic Resistance ◽  
Crop Production ◽  
Wastewater Treatment Plants ◽  
Antibiotic Resistance Genes ◽  
Treated Wastewater ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Vancomycin Resistant ◽  
Wastewater Samples ◽  
Selection Of

Abstract Treated wastewater discharged into the environment or reused in different activities can be a major vehicle for the transmission of antibiotic-resistant bacteria and antibiotic-resistance genes. In this study, environmental and wastewater samples, collected at different stages of treatment, were studied to identify the possibility of a positive selection of antibiotic-resistant organisms in wastewater treatment plants (WWTPs). Enterococci were isolated, characterized into the main human species, and subjected to the Kirby–Bauer test using seven antibiotics (five classes): ampicillin, chloramphenicol, ciprofloxacin, gentamicin, linezolid, tetracycline, and vancomycin. Furthermore, vancomycin-resistant enterococci (VRE), a major cause of nosocomial infection, was identified, and the genes vanA and vanB detected directly in the samples and in all confirmed VRE. Data showed that WWTPs were able to reduce the levels of antibiotic resistance, although 72% of the disinfected wastewaters still presented antibiotic-resistant enterococci. VRE were detected in 6% of the samples, including in reclaimed waters. UV disinfection was not effective at removing VRE and multiple antibiotic-resistant (MAR) enterococci, most commonly Enterococcus faecalis. The use of reclaimed water containing VRE and MAR enterococci in crop production, irrigation of urban gardens, and street cleaning increases immensely the potential risk to human health.

scholarly journals Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Susanne Schjørring ◽  
Karen A. Krogfelt
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Resistance Genes ◽  
Bacterial Flora ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Gi Tract ◽  
Antibiotic Resistant ◽  
Multiresistant Bacteria ◽  
Resistant Strains

We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes. The increased use of fermented food products and probiotics, as food supplements and health promoting products containing massive amounts of bacteria acting as either donors and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic resistance gene transfer occurring in the gut.

scholarly journals Future Prospects for Neisseria gonorrhoeae Treatment

2018 ◽  
Author(s):  
Beatriz Suay-García ◽  
María Teresa Pérez-Gracia
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Treatment Guidelines ◽  
Transmitted Disease ◽  
Alternative Therapies ◽  
Resistant Bacteria ◽  
High Morbidity ◽  
Antibiotic Resistant ◽  
Priority List ◽  
New Antibiotics ◽  
Resistant Strains

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

Phage Therapy: A Potential Solution for Antibiotic Resistance

2021 ◽  
Author(s):  
Chirag Choudhary ◽  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Biological Agents ◽  
Resistant Bacteria ◽  
Potential Solution ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
The Future

The idea of using a virus to kill bacteria may seem counterintuitive, but it may be the future of treating bacterial infections. Before the COVID-19 pandemic, one of the most frightening biological agents were so-called “superbugs” – antibiotic resistant bacteria – which could not be treated with conventional therapeutics. When antibiotics were first developed, they were hailed as a panacea. A panacea they were not.

scholarly journals Fosfomycin

2016 ◽  
Vol 29 (2) ◽  
pp. 321-347 ◽  
Author(s):  
Matthew E. Falagas ◽  
Evridiki K. Vouloumanou ◽  
George Samonis ◽  
Konstantinos Z. Vardakas
Keyword(s):  
Bacterial Infections ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
New Antibiotics

SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

scholarly journals Microbial Safety of Smoothie Drinks from Fresh Bars Collected in Slovakia

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 551
Author(s):  
Monika Krahulcová ◽  
Barbora Micajová ◽  
Petra Olejníková ◽  
Klára Cverenkárová ◽  
Lucia Bírošová
Keyword(s):  
Fruits And Vegetables ◽  
Food Service ◽  
Capital City ◽  
Coliform Bacteria ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
The Many ◽  
Klebsiella Spp

Among the many consumers in Slovakia, smoothies are nowadays gaining popularity. Smoothie drinks are prepared from raw fruits and vegetables. Therefore, their microbiological safety depends on hygiene standards. The aim of this work was to monitor and quantify selected sensitive and antibiotic-resistant microorganisms present in collected smoothies. Twenty analyzed smoothie samples were collected from six food service establishments (fresh bars) in the capital city of Slovakia, Bratislava. Antibiotic-resistant bacteria were found in at least one of each fresh bar. Antibiotic-resistant coliform bacteria prevailed, especially in green smoothies or juices containing more vegetable ingredients. Resistance to ampicillin, ciprofloxacin, tetracycline, chloramphenicol, and gentamicin was observed in the case of coliform bacteria. More than half of the smoothie drink samples did not contain resistant enterococci. On the other hand, vancomycin-resistant enterococci were detected in 20% of samples. The most frequently isolated antibiotic-resistant strains belonged to the Enterobacter spp. or Klebsiella spp. genus. In the last part of the work, the pretreatment effect of smoothie components on the selected microorganisms’ counts in the final product was investigated. Washing ingredients with an aqueous solution of a biocide agent containing silver and hydrogen peroxide proved to be the most effective way to decrease bacterial counts.

scholarly journals Essential Oils: A Natural Weapon against Antibiotic-Resistant Bacteria Responsible for Nosocomial Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 417
Author(s):  
Ramona Iseppi ◽  
Martina Mariani ◽  
Carla Condò ◽  
Carla Sabia ◽  
Patrizia Messi
Keyword(s):  
Essential Oils ◽  
Therapeutic Strategy ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Cupressus Sempervirens ◽  
Antibiotic Resistant ◽  
Agar Disc ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Better Than

The emergence of antibiotic-resistant bacteria has become a major concern worldwide. This trend indicates the need for alternative agents to antibiotics, such as natural compounds of plant origin. Using agar disc diffusion and minimum inhibitory concentration (MIC) assays, we investigated the antimicrobial activity of Citrus aurantium (AEO), Citrus x limon (LEO), Eucalyptus globulus (EEO), Melaleuca alternifolia (TTO), and Cupressus sempervirens (CEO) essential oils (EOs) against three representatives of antibiotic-resistant pathogens and respective biofilms: vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Using the checkerboard method, the efficacy of the EOs alone, in an association with each other, or in combination with the reference antibiotics was quantified by calculating fractional inhibitory concentrations (FICs). All the EOs displayed antibacterial activity against all strains to different extents, and TTO was the most effective. The results of the EO–EO associations and EO–antibiotic combinations clearly showed a synergistic outcome in most tests. Lastly, the effectiveness of EOs both alone and in association or combination against biofilm formed by the antibiotic-resistant strains was comparable to, and sometimes better than, that of the reference antibiotics. In conclusion, the combination of EOs and antibiotics represents a promising therapeutic strategy against antibiotic-resistant bacteria, even protected inside biofilms, which can allow decreasing the concentrations of antibiotics used.

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