scholarly journals Production of β-Lactamase Inhibitors by Streptomyces Species

Antibiotics ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 61 ◽  
Author(s):  
Daniela Viana Marques ◽  
Suellen Machado ◽  
Valéria Ebinuma ◽  
Carolina Duarte ◽  
Attilio Converti ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Streptomyces Species ◽  
Innovative Strategies ◽  
New Antibiotics ◽  
Microbial Products ◽  
Type Strains ◽  
Streptomyces Genus

β-Lactamase inhibitors have emerged as an effective alternative to reduce the effects of resistance against β-lactam antibiotics. The Streptomyces genus is known for being an exceptional natural source of antimicrobials and β-lactamase inhibitors such as clavulanic acid, which is largely applied in clinical practice. To protect against the increasing prevalence of multidrug-resistant bacterial strains, new antibiotics and β-lactamase inhibitors need to be discovered and developed. This review will cover an update about the main β-lactamase inhibitors producers belonging to the Streptomyces genus; advanced methods, such as genetic and metabolic engineering, to enhance inhibitor production compared with wild-type strains; and fermentation and purification processes. Moreover, clinical practice and commercial issues are discussed. The commitment of companies and governments to develop innovative strategies and methods to improve the access to new, efficient, and potentially cost-effective microbial products to combat the antimicrobial resistance is also highlighted.

scholarly journals Assessment of the Antibacterial Efficacy of Halicin against Pathogenic Bacteria

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1480
Author(s):  
Rayan Y. Booq ◽  
Essam A. Tawfik ◽  
Haya A. Alfassam ◽  
Ahmed J. Alfahad ◽  
Essam J. Alyamani
Keyword(s):  
Pathogenic Bacteria ◽  
Wide Spectrum ◽  
New Technology ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Bacterial Strains ◽  
Zones Of Inhibition

Artificial intelligence (AI) is a new technology that has been employed to screen and discover new drugs. Using AI, an anti-diabetic treatment (Halicin) was nominated and proven to have a unique antibacterial activity against several harmful bacterial strains, including multidrug-resistant bacteria. This study aims to explore the antibacterial effect of halicin and microbial susceptibility using the zone of inhibition and the minimum inhibition concentration (MIC) values while assessing the stability of stored halicin over a period of time with cost-effective and straightforward methods. Linear regression graphs were constructed, and the correlation coefficient was calculated. The new antibacterial agent was able to inhibit all tested gram-positive and gram-negative bacterial strains, but in different concentrations—including the A. baumannii multidrug-resistant (MDR) isolate. The MIC of halicin was found to be 16 μg/mL for S. aureus (ATCC BAA-977), 32 μg/mL for E. coli (ATCC 25922), 128 μg/mL for A. baumannii (ATCC BAA-747), and 256 μg/mL for MDR A. baumannii. Upon storage, the MICs were increased, suggesting instability of the drug after approximately a week of storage at 4 °C. MICs and zones of inhibition were found to be high (R = 0.90 to 0.98), suggesting that halicin has a promising antimicrobial activity and may be used as a wide-spectrum antibacterial drug. However, the drug’s pharmacokinetics have not been investigated, and further elucidation is needed.

scholarly journals Metabolic profiling and antibacterial activity of Eryngium pristis Cham. & Schltdl. - prospecting for its use in the treatment of bacterial infections

2021 ◽  
Vol 5 (1) ◽  
pp. 020-028
Author(s):  
Fernandes Laura Silva ◽  
da Costa Ygor Ferreira Garcia ◽  
de Bessa Martha Eunice ◽  
Ferreira Adriana Lucia Pires ◽  
do Amaral Corrêa José Otávio ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bioactive Compounds ◽  
Metabolic Profile ◽  
Bacterial Infections ◽  
Ethanolic Extract ◽  
Multidrug Resistant ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
New Antibiotics

Morbidity and mortality of the infected patients by multidrug-resistant bacteria have increased, emphasizing the urgency of fight for the discovery of new innovative antibiotics. In this sense, natural products emerge as valuable sources of bioactive compounds. Among the biodiversity, Eryngium pristis Cham. & Schltdl. (Apiaceae Lindl.) is traditionally used to treat thrush and ulcers of throat and mouth, as diuretic and emmenagogue, but scarcely known as an antimicrobial agent. With this context in mind, the goals of this study were to investigate the metabolic profile and the antibacterial activity of ethanolic extract (EE-Ep) and hexane (HF-Ep), dichloromethane (DF-Ep), ethyl acetate (EAF-Ep) and butanol (BF-Ep) fractions from E. pristis leaves. Gas Chromatography-Mass Spectrometry (GC-MS) was performed to stablish the metabolic profile and revealed the presence of 12 and 14 compounds in EAF-Ep and HF-Ep, respectively. β-selinene, spathulenol, globulol, 2-methoxy-4-vinylphenol, α-amyrin, β-amyrin, and lupeol derivative were some of phytochemicals identified. The antibacterial activity was determined by Minimal Inhibitory Concentration (MIC) using the broth micro-dilution against eight ATCC® and five methicillin-resistant Staphylococcus aureus (MRSA) clinical strains. HF-Ep was the most effective (MIC ≤ 5,000 µg/µL), being active against the largest part of tested Gram-positive and Gram-negative bacterial strains, including MRSA, with exception of Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 9027) and (ATCC 27853). These results suggest that E. pristis is a natural source of bioactive compounds for the search of new antibiotics which can be an interesting therapeutic approach to recover patients mainly infected by MRSA strains.

scholarly journals Innovative Strategies for Developing Tuberculosis Implementation Research in Sudan

2020 ◽  
Author(s):  
Ayman Ahmed Elshayeb ◽  
Nihad Mohammed Ahmed ◽  
Karimeldin Mohammed Salih ◽  
Osama Abu Zaid Nugoud ◽  
Abd Allah Elnayeb Yagoub ◽  
...  
Keyword(s):  
Implementation Research ◽  
Targeted Delivery ◽  
National Level ◽  
Multidrug Resistant ◽  
World Health ◽  
Strategy Development ◽  
Bacterial Strains ◽  
Innovative Strategies ◽  
General Program ◽  
Health Organization

Abstract Introduction: Sudan, especially Eastern States are very poor areas at great risk of endemic and communicable diseases particularly tuberculosis. The reasons for the spread and transmission of this disease include medical, economical and geographical issues, besides Sudan’s location in the middle of nine countries in East Africa, its boundaries were affected by free movement, high number of conflicts displaced peoples from boarders’ countries, high illiteracy rates, limited financial resources and shortages in medical services. Objectives: This project is conducted to implement a new developed system for eliminating Tuberculosis infections among eastern Sudanese populations focusing on the eradication of multidrug resistant Mycobacterium tuberculosis including novel methods for the targeted delivery of new therapeutic drugs. Conceptual Methodology: Strategies adopted in this work are proposed to increase access includes to communicable and economic factors. Disease Survey and Laboratorial Investigation for Multi Drug Resistant bacterial strains confirmation. Medical Assessment of TB Patients to facilitate improved efficiencies through metric measurement and enable patients’ relationship management. Established a national level policy of treatment, vaccination and prevention. Administering regular evaluation of the disease situation and control.Results: Implementation outcomes includes the conceptual framework for this project were informed by a combination of the general program logic model, the health system framework of the World Health Organization, WHO, the pillars of the Sudan health agenda, and the framework of the Strategic Elimination Plan. It is assumed that the reduction of TB burden at the national level (long-term output or impact) is preceded by improved case-finding and case-holding practices (short-term output). Impact outcome of the project is derived from the observation that tuberculosis is much more common at the boarders than center of Sudan where no adequate clinical services are available. It is conceivable that, although outbreaks may occur periodically, the control of disease might be easier to overcome than direct medication.Conclusion: A major success of the project accomplishment, is the stimulation of the implementation strategy development for elimination and eradication of Tuberculosis in Sudan with a view to bring diagnostic and surveillance issues much higher up according to the implementation research agenda especially for those areas explored with similar national and international research projects, reports and technical initiatives.

scholarly journals Design of a Broad-Range Bacteriophage Cocktail That ReducesPseudomonas aeruginosaBiofilms and Treats Acute Infections in Two Animal Models

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Francesca Forti ◽  
Dwayne R. Roach ◽  
Marco Cafora ◽  
Maria E. Pasini ◽  
David S. Horner ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Cost Effective ◽  
The United States ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Content Type ◽  
Clinical Strains ◽  
Phage Cocktail ◽  
The Individual

ABSTRACTThe alarming diffusion of multidrug-resistant (MDR) bacterial strains requires investigations on nonantibiotic therapies. Among such therapies, the use of bacteriophages (phages) as antimicrobial agents, namely, phage therapy, is a promising treatment strategy supported by the findings of recent successful compassionate treatments in Europe and the United States. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains ofPseudomonas aeruginosa, including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance. We demonstrated that the cocktail composed of four novel phages (PYO2, DEV, E215 and E217) and two previously characterized phages (PAK_P1 and PAK_P4) was able to lyseP. aeruginosaboth in planktonic liquid cultures and in biofilms. In addition, we showed that the phage cocktail could cure acute respiratory infection in mice and treat bacteremia in wax moth (Galleria mellonella) larvae. Furthermore, administration of the cocktail to larvae prior to bacterial infection provided prophylaxis. In this regard, the efficiency of the phage cocktail was found to be unaffected by the MDR or mucoid phenotype of the pseudomonal strain. The cocktail was found to be superior to the individual phages in destroying biofilms and providing a faster treatment in mice. We also found theGallerialarva model to be cost-effective for testing the susceptibility of clinical strains to phages, suggesting that it could be implemented in the frame of developing personalized phage therapies.

scholarly journals New and Potent Quinuclidine-Based Antimicrobial Agents

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2675 ◽  
Author(s):  
Andreja Radman Kastelic ◽  
Renata Odžak ◽  
Iskra Pezdirc ◽  
Karlo Sović ◽  
Tomica Hrenar ◽  
...  
Keyword(s):  
Biological Activity ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Activity Data ◽  
Gram Negative ◽  
Quaternary Compounds ◽  
New Antibiotics ◽  
Spectrum Activity

Developing new antibiotics is currently very important since antibiotic resistance is one of the biggest problems of global health today. In the search for a new class of potential antimicrobial agents, ten new compounds were designed and synthesized based on the quinuclidinium heterocyclic core and the oxime functional group. The antimicrobial activity was assessed against a panel of representative gram-positive and gram-negative bacteria. All compounds demonstrated potent activity against the tested microorganisms, with the minimum inhibitory concentration (MIC) values ranging from 0.25 to 256.00 μg/mL. Among the tested compounds, two quaternary compounds, para-N-chlorobenzyl and meta-N-bromobenzyl quinuclidinium oximes, displayed the most potent and broad-spectrum activity against both gram-positive and gram-negative bacterial strains (MIC values from 0.25 to 4.00 μg/mL), with the lowest value for the important multidrug resistant gram-negative pathogen Pseudomonas aeruginosa. In the case of Klebsiella pneumoniae, activity of those compounds are 256-fold and 16-fold better than gentamicin, respectively. MTT assays showed that compounds are nontoxic for human cell lines. Multi-way analysis was used to separately reduce dimensionality of quantum chemical data and biological activity data to obtain a regression model and the required parameters for the enhancement of biological activity.

scholarly journals New Antibiotics for Multidrug-Resistant Bacterial Strains: Latest Research Developments and Future Perspectives

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2671
Author(s):  
Marco Terreni ◽  
Marina Taccani ◽  
Massimo Pregnolato
Keyword(s):  
Antibiotic Resistance ◽  
Chemical Compounds ◽  
Multidrug Resistant ◽  
Phase Iii ◽  
Fourth Generation ◽  
Careful Examination ◽  
Bacterial Strains ◽  
New Agents ◽  
Pharmacological Interest ◽  
New Antibiotics

The present work aims to examine the worrying problem of antibiotic resistance and the emergence of multidrug-resistant bacterial strains, which have now become really common in hospitals and risk hindering the global control of infectious diseases. After a careful examination of these phenomena and multiple mechanisms that make certain bacteria resistant to specific antibiotics that were originally effective in the treatment of infections caused by the same pathogens, possible strategies to stem antibiotic resistance are analyzed. This paper, therefore, focuses on the most promising new chemical compounds in the current pipeline active against multidrug-resistant organisms that are innovative compared to traditional antibiotics: Firstly, the main antibacterial agents in clinical development (Phase III) from 2017 to 2020 are listed (with special attention on the treatment of infections caused by the pathogens Neisseria gonorrhoeae, including multidrug-resistant isolates, and Clostridium difficile), and then the paper moves on to the new agents of pharmacological interest that have been approved during the same period. They include tetracycline derivatives (eravacycline), fourth generation fluoroquinolones (delafloxacin), new combinations between one β-lactam and one β-lactamase inhibitor (meropenem and vaborbactam), siderophore cephalosporins (cefiderocol), new aminoglycosides (plazomicin), and agents in development for treating drug-resistant TB (pretomanid). It concludes with the advantages that can result from the use of these compounds, also mentioning other approaches, still poorly developed, for combating antibiotic resistance: Nanoparticles delivery systems for antibiotics.

scholarly journals Innovative Strategies for Developing Tuberculosis Implementation Research in Sudan

2020 ◽  
Author(s):  
Ayman Ahmed Elshayeb ◽  
Nihad Mohammed Ahmed ◽  
Karimeldin Mohammed Salih ◽  
Osama Abu Zaid Nugoud ◽  
Abd Allah Elnayeb Yagoub ◽  
...  
Keyword(s):  
Implementation Research ◽  
Targeted Delivery ◽  
National Level ◽  
Multidrug Resistant ◽  
World Health ◽  
Strategy Development ◽  
Bacterial Strains ◽  
Innovative Strategies ◽  
General Program ◽  
Health Organization

Abstract Introduction: Sudan, especially Eastern States are very poor areas at great risk of endemic and communicable diseases particularly tuberculosis. The reasons for the spread and transmission of this disease include medical, economical and geographical issues, besides Sudan’s location in the middle of nine countries in East Africa, its boundaries were affected by free movement, high number of conflicts displaced peoples from boarders’ countries, high illiteracy rates, limited financial resources and shortages in medical services. Objectives: This project is conducted to implement a new developed system for eliminating Tuberculosis infections among eastern Sudanese populations focusing on the eradication of multidrug resistant Mycobacterium tuberculosis including novel methods for the targeted delivery of new therapeutic drugs. Methods: Strategies adopted in this work are proposed to increase access includes to communicable and economic factors. Disease Survey and Laboratorial Investigation for Multi Drug Resistant bacterial strains confirmation. Medical Assessment of TB Patients to facilitate improved efficiencies through metric measurement and enable patients’ relationship management. Established a national level policy of treatment, vaccination and prevention. Administering regular evaluation of the disease situation and control.Results: Implementation outcomes includes the conceptual framework for this project were informed by a combination of the general program logic model, the health system framework of the World Health Organization, WHO, the pillars of the Sudan health agenda, and the framework of the Strategic Elimination Plan. It is assumed that the reduction of TB burden at the national level (long-term output or impact) is preceded by improved case-finding and case-holding practices (short-term output). Impact outcome of the project is derived from the observation that tuberculosis is much more common at the boarders than center of Sudan where no adequate clinical services are available. It is conceivable that, although outbreaks may occur periodically, the control of disease might be easier to overcome than direct medication.Conclusion: A major success of the project accomplishment, is the stimulation of the implementation strategy development for elimination and eradication of Tuberculosis in Sudan with a view to bring diagnostic and surveillance issues much higher up according to the implementation research agenda especially for those areas explored with similar national and international research projects, reports and technical initiatives.

The CSF p-tau181/Aβ42 Ratio Offers a Good Accuracy “In Vivo” in the Differential Diagnosis of Alzheimer’s Dementia

2019 ◽  
Vol 16 (7) ◽  
pp. 587-595 ◽  
Author(s):  
Roberto Santangelo ◽  
Alessandro Dell'Edera ◽  
Arianna Sala ◽  
Giordano Cecchetti ◽  
Federico Masserini ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Diagnosis ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Cost Effective ◽  
Daily Clinical Practice ◽  
Different Types ◽  
Experimental Trials ◽  
Csf Findings

Background: The incoming disease-modifying therapies against Alzheimer’s disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-β 42 (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau181), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption. Methods: We measured CSF AD biomarkers’ concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings. Results: A p-tau181/Aβ42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FDG-PET partially agreed with the p-tau181/Aβ42 ratio, thus determining an increase in CSF accuracy. Conclusions: The p-tau181/Aβ42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.

The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation

2020 ◽  
Vol 16 (4) ◽  
pp. 389-401 ◽  
Author(s):  
Hanane Boucherit ◽  
Abdelouahab Chikhi ◽  
Abderrahmane Bensegueni ◽  
Amina Merzoug ◽  
Jean-Michel Bolla
Keyword(s):  
Virtual Screening ◽  
Bacterial Survival ◽  
Methionine Aminopeptidase ◽  
Bacterial Strains ◽  
Microdilution Method ◽  
Zinc Database ◽  
Promising Target ◽  
New Antibiotics ◽  
Potential Inhibitors

Background: The great emergence of multi-resistant bacterial strains and the low renewal of antibiotics molecules are leading human and veterinary medicine to certain therapeutic impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a promising target for developing new antibiotics because it is essential for bacterial survival. Objective: To screen for potential MetAP inhibitors by in silico virtual screening of the ZINC database and evaluate the best potential lead molecules by in vitro studies. Methods: We have considered 200,000 compounds from the ZINC database for virtual screening with FlexX software to identify potential inhibitors against bacterial MetAP. Nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each inhibitor of MetAP was tested by the disc-diffusion assay against one Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli & Pseudomonas aeruginosa) bacteria. Among the studied compounds, compounds ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results. Results: These results suggest compounds ZINC04785369 and ZINC03307916 as promising molecules for developing MetAP inhibitors. Conclusion: Furthermore, they could therefore serve as lead molecules for further chemical modifications to obtain clinically useful antibacterial agents.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

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