scholarly journals Toward Autonomous Antibiotic Discovery

mSystems ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Cesar de la Fuente-Nunez
Keyword(s):  
Molecular Diversity ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Natural World ◽  
Resistant Bacteria ◽  
Computational Power ◽  
Molecular Scaffolds ◽  
Life Saving ◽  
Antibiotic Discovery ◽  
Global Health Challenge

ABSTRACT Machines hold the potential to replace humans in many societal endeavors, and drug discovery is no exception. Antibiotic innovation has been stalled for decades, which has coincided with an alarming increase in multidrug-resistant bacteria. Since the beginning of the antibiotic era, the natural world has been our greatest innovator, giving rise to nearly all antibiotics available today. As mere observers of the vast molecular diversity produced by Earth’s organisms, we have perfected the art of isolating novel chemistries with life-saving antimicrobial properties. However, today we are at a crossroads, as no new molecular scaffolds have been discovered for decades. We may need to look beyond the natural world into the virtual dimension for solutions and harness present-day computational power to help solve the grand global health challenge of antibiotic resistance. Computer-made drugs may enable the discovery of unprecedented functions in biological systems and help replenish our arsenal of effective antibiotics.

Combining antibiotics with silver nanoparticles: A potential treatment strategy against antimicrobial resistance

2021 ◽  
pp. 1-22
Author(s):  
Maryam Afridi ◽  
Saeed Ahmad Khan ◽  
Ruqayya Afridi ◽  
Farman Ullah ◽  
Abdul Majid ◽  
...  
Keyword(s):  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Resistant Organism ◽  
Antibacterial Resistance ◽  
Current Crisis ◽  
Mortality And Morbidity ◽  
Multidrug Resistant Organisms ◽  
Attractive Option ◽  
Silver Nps

Growing resistance to currently approved antibiotics is posing serious concern worldwide. The multidrug-resistant organisms are a major cause of mortality and morbidity around the globe. The limited options to treat infections caused by resistant organism requires alternative strategies to increase the effectiveness of antibiotic for better clinical outcomes. Recent advances in nanotechnology have enabled the drugs to be used in nanoscale to increase the effectiveness of antibiotics. The use of nanoparticles to treat infectious diseases has a long history in the pharmaceutical market, and the versatility of these particles to incorporate various materials as carriers make it an attractive option to combat the current crisis of emerging antibacterial resistance. Silver, a metal with many medical applications, has inherent antimicrobial properties. Therefore, silver NPs are appearing as one of the best options to be used in combination with antibiotics to increase effectiveness against resistant bacteria. Here, we discuss the applications and mechanisms of silver NPs to treat microbial resistance in light of recent research.

scholarly journals Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR)

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Najwan Jubair ◽  
Mogana Rajagopal ◽  
Sasikala Chinnappan ◽  
Norhayati Binti Abdullah ◽  
Ayesha Fatima
Keyword(s):  
Secondary Metabolites ◽  
Plant Secondary Metabolites ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Resistance Strategies ◽  
Microbial Infections ◽  
Ancient Times ◽  
Antibiotic Discovery

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.

scholarly journals Urban brown rats (Rattus norvegicus) as possible source of multidrug-resistant Enterobacteriaceae and meticillin-resistant Staphylococcus spp., Vienna, Austria, 2016 and 2017

2019 ◽  
Vol 24 (32) ◽  
Author(s):  
Amélie Desvars-Larrive ◽  
Werner Ruppitsch ◽  
Sarah Lepuschitz ◽  
Michael P Szostak ◽  
Joachim Spergser ◽  
...  
Keyword(s):  
Rattus Norvegicus ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
New Delhi ◽  
Rodent Control ◽  
Carbapenem Resistant ◽  
Modern Cities ◽  
Close Proximity ◽  
Staphylococcus Spp

Background Brown rats (Rattus norvegicus) are an important wildlife species in cities, where they live in close proximity to humans. However, few studies have investigated their role as reservoir of antimicrobial-resistant bacteria. Aim We intended to determine whether urban rats at two highly frequented sites in Vienna, Austria, carry extended-spectrum β-lactamase-producing Enterobacteriaceae, fluoroquinolone-resistant Enterobacteriaceae and meticillin-resistant (MR) Staphylococcus spp. (MRS). Methods We surveyed the presence of antimicrobial resistance in 62 urban brown rats captured in 2016 and 2017 in Vienna, Austria. Intestinal and nasopharyngeal samples were cultured on selective media. We characterised the isolates and their antimicrobial properties using microbiological and genetic methods including disk diffusion, microarray analysis, sequencing, and detection and characterisation of plasmids. Results Eight multidrug-resistant Escherichia coli and two extensively drug-resistant New Delhi metallo-β-lactamases-1 (NDM-1)-producing Enterobacter xiangfangensis ST114 (En. cloacae complex) were isolated from nine of 62 rats. Nine Enterobacteriaceae isolates harboured the bla CTX-M gene and one carried a plasmid-encoded ampC gene (bla CMY-2). Forty-four MRS were isolated from 37 rats; they belonged to seven different staphylococcal species: S. fleurettii, S. sciuri, S. aureus, S. pseudintermedius, S. epidermidis, S. haemolyticus (all mecA-positive) and mecC-positive S. xylosus. Conclusion Our findings suggest that brown rats in cities are a potential source of multidrug-resistant bacteria, including carbapenem-resistant En. xiangfangensis ST114. Considering the increasing worldwide urbanisation, rodent control remains an important priority for health in modern cities.

scholarly journals Antibacterial Peptide Nucleic Acids—Facts and Perspectives

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 559 ◽  
Author(s):  
Monika Wojciechowska ◽  
Marcin Równicki ◽  
Adam Mieczkowski ◽  
Joanna Miszkiewicz ◽  
Joanna Trylska
Keyword(s):  
Peptide Nucleic Acid ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antibacterial Studies ◽  
Compound Libraries ◽  
Alternative Approach ◽  
The Common ◽  
Time Required ◽  
Antibiotic Discovery

Antibiotic resistance is an escalating, worldwide problem. Due to excessive use of antibiotics, multidrug-resistant bacteria have become a serious threat and a major global healthcare problem of the 21st century. This fact creates an urgent need for new and effective antimicrobials. The common strategies for antibiotic discovery are based on either modifying existing antibiotics or screening compound libraries, but these strategies have not been successful in recent decades. An alternative approach could be to use gene-specific oligonucleotides, such as peptide nucleic acid (PNA) oligomers, that can specifically target any single pathogen. This approach broadens the range of potential targets to any gene with a known sequence in any bacterium, and could significantly reduce the time required to discover new antimicrobials or their redesign, if resistance arises. We review the potential of PNA as an antibacterial molecule. First, we describe the physicochemical properties of PNA and modifications of the PNA backbone and nucleobases. Second, we review the carriers used to transport PNA to bacterial cells. Furthermore, we discuss the PNA targets in antibacterial studies focusing on antisense PNA targeting bacterial mRNA and rRNA.

scholarly journals Nanostructured Antimicrobial Peptides: Crucial Steps of Overcoming the Bottleneck for Clinics

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhanyi Yang ◽  
Shiqi He ◽  
Hua Wu ◽  
Ting Yin ◽  
Lili Wang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Controlled Release ◽  
Antimicrobial Peptides ◽  
Biological Activities ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Great Promise ◽  
Resistant Bacteria ◽  
Biological Stability ◽  
Security Issue

The security issue of human health is faced with dispiriting threats from multidrug-resistant bacteria infections induced by the abuse and misuse of antibiotics. Over decades, the antimicrobial peptides (AMPs) hold great promise as a viable alternative to treatment with antibiotics due to their peculiar antimicrobial mechanisms of action, broad-spectrum antimicrobial activity, lower drug residue, and ease of synthesis and modification. However, they universally express a series of disadvantages that hinder their potential application in the biomedical field (e.g., low bioavailability, poor protease resistance, and high cytotoxicity) and extremely waste the abundant resources of AMP database discovered over the decades. For all these reasons, the nanostructured antimicrobial peptides (Ns-AMPs), based on a variety of nanosystem modification, have made up for the deficiencies and pushed the development of novel AMP-based antimicrobial therapies. In this review, we provide an overview of the advantages of Ns-AMPs in improving therapeutic efficacy and biological stability, reducing side effects, and gaining the effect of organic targeting and drug controlled release. Then the different material categories of Ns-AMPs are described, including inorganic material nanosystems containing AMPs, organic material nanosystems containing AMPs, and self-assembled AMPs. Additionally, this review focuses on the Ns-AMPs for the effect of biological activities, with emphasis on antimicrobial activity, biosecurity, and biological stability. The “state-of-the-art” antimicrobial modes of Ns-AMPs, including controlled release of AMPs under a specific environment or intrinsic antimicrobial properties of Ns-AMPs, are also explicated. Finally, the perspectives and conclusions of the current research in this field are also summarized.

scholarly journals A Precautionary Approach to Guide the Use of Transition Metal-Based Nanotechnology to Prevent Orthopedic Infections

Materials ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 314 ◽  
Author(s):  
Marta Bottagisio ◽  
Arianna Lovati ◽  
Fabio Galbusera ◽  
Lorenzo Drago ◽  
Giuseppe Banfi
Keyword(s):  
Uv Light ◽  
Antimicrobial Properties ◽  
Basic Research ◽  
Orthopedic Implants ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ros Generation ◽  
Antibiotic Resistant ◽  
Almost All

The increase of multidrug-resistant bacteria remains a global concern. Among the proposed strategies, the use of nanoparticles (NPs) alone or associated with orthopedic implants represents a promising solution. NPs are well-known for their antimicrobial effects, induced by their size, shape, charge, concentration and reactive oxygen species (ROS) generation. However, this non-specific cytotoxic potential is a powerful weapon effective against almost all microorganisms, but also against eukaryotic cells, raising concerns related to their safe use. Among the analyzed transition metals, silver is the most investigated element due to its antimicrobial properties per se or as NPs; however, its toxicity raises questions about its biosafety. Even though it has milder antimicrobial and cytotoxic activity, TiO2 needs to be exposed to UV light to be activated, thus limiting its use conjugated to orthopedic devices. By contrast, gold has a good balance between antimicrobial activity as an NP and cytocompatibility because of its inability to generate ROS. Nevertheless, although the toxicity and persistence of NPs within filter organs are not well verified, nowadays, several basic research on NP development and potential uses as antimicrobial weapons is reported, overemphasizing NPs potentialities, but without any existing potential of translation in clinics. This analysis cautions readers with respect to regulation in advancing the development and use of NPs. Hopefully, future works in vivo and clinical trials will support and regulate the use of nano-coatings to guarantee safer use of this promising approach against antibiotic-resistant microorganisms.

Pimarane-type Diterpenes Obtained by Biotransformation: Antimicrobial Properties Against Clinically Isolated Gram-positive Multidrug-resistant Bacteria

2012 ◽  
pp. n/a-n/a ◽  
Author(s):  
Thiago S. Porto ◽  
Marília R. Simão ◽  
Lucas Z. Carlos ◽  
Carlos H. G. Martins ◽  
Niege A. J. C. Furtado ◽  
...  
Keyword(s):  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Positive
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