scholarly journals Antibody-Recruiting Protein-Catalyzed Capture Agents to Combat Antibiotic-Resistant Bacteria

2019 ◽  
Author(s):  
Matthew N. Idso ◽  
Ajay Suresh Akhade ◽  
Mario L. Arrieta-Ortiz ◽  
Bert T. Lai ◽  
Vivek Srinivas ◽  
...  

AbstractAntibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial PCC technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant Klebsiella pneumoniae, an opportunistic gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of K. pneumoniae for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC50∼50 nM) to full-length MrkA, and selectively bound to MrkA-expressing K. pneumoniae, but not to other pathogenic bacterial species. AR-PCCs conjugated with immunogens promoted antibody recruitment to K. pneumoniae, leading to phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria.

Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.


2018 ◽  
Vol 22 (04) ◽  
pp. 49-56

ASIA – Natural products identified as potential new antibiotic against various drug-resistant bacteria. ASIA – HKUST discovers new antibiotics resistance mechanism. ASIA – Green tea-based drug carriers improve cancer treatment. ASIA – New molecule can kill five types of deadly drug-resistant superbugs. ASIA – Scientists grow liver cancer cells in lab. ASIA – New findings reveal sex-based and age-based differences in how the gut microbiome affects brain immunity. ASIA – HKUST scientists find new way to produce chiral molecules.


2012 ◽  
Vol 78 (8) ◽  
pp. 2768-2774 ◽  
Author(s):  
Ashley N. Brown ◽  
Kathryn Smith ◽  
Tova A. Samuels ◽  
Jiangrui Lu ◽  
Sherine O. Obare ◽  
...  

ABSTRACTWe show here that silver nanoparticles (AgNP) were intrinsically antibacterial, whereas gold nanoparticles (AuNP) were antimicrobial only when ampicillin was bound to their surfaces. Both AuNP and AgNP functionalized with ampicillin were effective broad-spectrum bactericides against Gram-negative and Gram-positive bacteria. Most importantly, when AuNP and AgNP were functionalized with ampicillin they became potent bactericidal agents with unique properties that subverted antibiotic resistance mechanisms of multiple-drug-resistant bacteria.


2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Iyanuoluwa Mola ◽  
Adeola Onibokun ◽  
Solomon Oranusi

Foods are essential vehicles in human exposure to antibiotic resistant bacteria which serve as reservoirs for resistance genes and a rising food safety concern. Antimicrobial resistance, including multidrug resistance (MDR), is an increasing problem globally and poses a serious concern to human health. This study was designed to synthesize data regarding the prevalence of MDR bacteria associated with foods and drinks sold within Nigeria in order to contribute to the existing findings in this area. A comprehensive literature search on the prevalence of multi-drug resistant bacteria associated with foods and drinks in Nigeria from 2015 to 2020 was conducted using three databases; PubMed, Science Direct and Scopus. After screening and selection, 26 out of 82 articles were used for the qualitative data synthesis. Of the total of one thousand three hundred and twenty-six MDR bacteria reportedly isolated in all twenty-six articles, the highest prevalence (660) was observed in drinks, including water, while the lowest (20) was observed in the article which combined results for both protein and vegetable-based foods. Escherichia sp. had the most frequency of occurrence, appearing as MDR bacteria in ten out of the twenty-six articles. Salmonella sp. appeared as MDR in seven out of the twenty-six articles included in this study, in all seven articles where it was reported, it had the highest percentage (85.4%) prevalence as MDR bacteria. Public health personnel need to ensure critical control during the production and handling of foods and drinks, as well as create more awareness on proper hygienic practices to combat the spread of MDR bacteria.


2020 ◽  
Vol 21 (2) ◽  
pp. 425 ◽  
Author(s):  
Pilar Domingo-Calap ◽  
Beatriz Beamud ◽  
Justine Vienne ◽  
Fernando González-Candelas ◽  
Rafael Sanjuán

The emergence of multi-drug-resistant bacteria represents a major public-health threat. Phages constitute a promising alternative to chemical antibiotics due to their high host specificity, abundance in nature, and evolvability. However, phage host specificity means that highly diverse bacterial species are particularly difficult to target for phage therapy. This is the case of Klebsiella pneumoniae, which presents a hypervariable extracellular matrix capsule exhibiting dozens of variants. Here, we report four novel phages infecting K. pneumoniae capsular type K22 which were isolated from environmental samples in Valencia, Spain. Full genome sequencing showed that these phages belong to the Podoviridae family and encode putative depolymerases that allow digestion of specific K22 K. pneumoniae capsules. Our results confirm the capsular type-specificity of K. pneumoniae phages, as indicated by their narrow infectivity in a panel of K. pneumoniae clinical isolates. Nonetheless, this work represents a step forward in the characterization of phage diversity, which may culminate in the future use of large panels of phages for typing and/or for combating multi-drug-resistant K. pneumoniae.


2021 ◽  
Vol 15 (10) ◽  
pp. 2506-2511
Author(s):  
Nayyab Sultan ◽  
Sabahat Javaid Butt ◽  
Wajeeha Mehak ◽  
Samreen Qureshi ◽  
Syed Hamza Abbas ◽  
...  

Antibiotics have played a crucial role in the treatment of bacterial infections. Past few decades are marked with advancement of multidrug resistant (MDR) pathogens, which have endangered antibiotic’s therapeutic efficacy. Scientific world is now struggling with the crisis of MDR pathogens. This supreme matter demands careful attention or otherwise it would jeopardize clinical management of infectious diseases. Implication of alternative approaches can pave a new way in the treatment of these troublesome bacteria. Tea leaves are known to pose antibacterial activity against many pathogenic microorganisms. This review has summarized the antibacterial potential of tea leave’s extracts against resistant bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Acenitobacter spp, Campylobacter spp. Consumption of natural products such as tea may very well replace, minimize or obliterate this complicated situation. Keywords: Anti-bacterial, Tea, Camellia sinensis, Drug resistant bacteria, Antibiotic resistant bacteria, Synergism, Polyphenols.


1999 ◽  
Vol 556 ◽  
Author(s):  
C.-I Chen ◽  
A. Meike ◽  
Y.-J. Chuu ◽  
A. Sawvel ◽  
W. Lin

AbstractTransport of bacteria is investigated as part of the Large-Block Test (LBT), a thermally perturbed block of Topopah Spring tuff. Two bacterial species,Bacillus subtilisandArthrobacter oxydans, were isolated from the Yucca Mountain tuff. Natural mutants that can grow under the simultaneous presence of the two antibiotics, streptomycin and rifampicin, were selected from these species by laboratory procedures, cultured, and injected into the five heater boreholes of the large block hours before heating was initiated. The temperature, as measured 5 cm above one of the heater boreholes, rose slowly over a matter of months to a maximum of 142°C and to 60°C at the top and the bottom of the block. Samples were collected from boreholes located approximately 5 ft below the injection points. Double-drug-resistant bacteria were found in the collection boreholes nine months after injection. Biochemical tests support the identification ofB. subtilisin the collection boreholes. Double-drug-resistant microbes also appeared in the heater boreholes where the temperature had been sustainably high throughout the test. The number of double-drugresistant bacteria that were identified in the collection boreholes increased with time until the heater was deactivated. Negative indications in the collection holes after the heater was deactivated support the supposition that these bacteria were the species that were injected. An apparent homogeneous distribution among the collection boreholes suggests no pattern to the migration of bacteria through the block. The relationship between bacterial migration and the movement of water is not yet understood. These observations indicate the possibility of rapid bacterial transport in a thermally perturbed geologic setting. The implications for colloid transport need to be reviewed.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Jitender Yadav ◽  
Sana Ismaeel ◽  
Ayub Qadri

ABSTRACT Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of Salmonella and at least two other Gram-negative bacteria in vitro. This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.


Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-32
Author(s):  
Zifang Shang ◽  
Siew Yin Chan ◽  
Qing Song ◽  
Peng Li ◽  
Wei Huang

The emerging antimicrobial resistance (AMR) poses serious threats to the global public health. Conventional antibiotics have been eclipsed in combating with drug-resistant bacteria. Moreover, the developing and deploying of novel antimicrobial drugs have trudged, as few new antibiotics are being developed over time and even fewer of them can hit the market. Alternative therapeutic strategies to resolve the AMR crisis are urgently required. Pathogen-oriented therapy (POT) springs up as a promising approach in circumventing antibiotic resistance. The tactic underling POT is applying antibacterial compounds or materials directly to infected regions to treat specific bacteria species or strains with goals of improving the drug efficacy and reducing nontargeting and the development of drug resistance. This review exemplifies recent trends in the development of POTs for circumventing AMR, including the adoption of antibiotic-antibiotic conjugates, antimicrobial peptides, therapeutic monoclonal antibodies, nanotechnologies, CRISPR-Cas systems, and microbiota modulations. Employing these alternative approaches alone or in combination shows promising advantages for addressing the growing clinical embarrassment of antibiotics in fighting drug-resistant bacteria.


Author(s):  
Haragouri Mishra ◽  
Amulyaratna Behera ◽  
Sidhartha Sankar Kar ◽  
Gurudutta Pattnaik ◽  
Satish Kanhar ◽  
...  

The rapid development of drug resistant micro-organisms is a challenge to the mankind. Nano formulated compounds have proved to be effective strategy to combat bacterial drug resistance. Currently nanoparticulate systems such as nanoantibiotics are getting major attention due to their low inherent toxicity, biodegradability, bioincompatibility and tuneable mechanical characteristics. Nano formulated antibiotics are generally obtained by emulsification and gelification techniques. The effective uses of polymers in encapsulation of antibiotics show enhancement of the efficacy of antibiotics. Combined with techniques like diffraction laser spectroscopy (DLS), electron microscopy (EM) and atomic force microscopy (AFM), morphological research of nanoformulated antibiotics are conducted. The detailed study of the polymers used in the preparation of antibiotics nanoparticles as well as their impact on interactions is done by bio-analytical techniques. Antibiotics attached to nanoparticles can avoid the action of enzymes produced by drug resistant bacteria.  Nano antibiotics show higher efficacy and bioavailability so a lot of new formulations using nano methods can be developed with the help of bioanalytical techniques. The development as well as the estimation of antibiotics prepared as nano-formulations as per the recent advanced techniques is illustrated in this review.


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