Removal of Anti---Galactosyl Antibodies Elicits Protective Immunity Against Gram-Negative Bacterial Infections

2018 ◽  
Author(s):  
Daniel Bello-Gil ◽  
Magdiel Perez-Cruz ◽  
Cristina Costa ◽  
Mariana Camoez ◽  
Angeles Dominguez ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Bacterial Infections ◽  
Gram Negative

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals The antimicrobial potential of cannabidiol

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Angela M. Kavanagh ◽  
Alysha G. Elliott ◽  
Bing Zhang ◽  
Soumya Ramu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Modern Medicine ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
New Class ◽  
Clostridioides Difficile ◽  
Excellent Activity ◽  
Induce Resistance ◽  
First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

2021 ◽  
Author(s):  
Byungji Kim ◽  
Qinglin Yang ◽  
Leslie W. Chan ◽  
Sangeeta N. Bhatia ◽  
Erkki Ruoslahti ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Broad Spectrum ◽  
Therapeutic Efficacy ◽  
Bacterial Infections ◽  
Silicon Nanoparticles ◽  
First Line ◽  
Gram Positive ◽  
Gram Negative ◽  
Porous Silicon Nanoparticles

RNAi-mediated immunotherapy provided by fusogenic porous silicon nanoparticles demonstrates superior therapeutic efficacy against both Gram-positive and Gram-negative bacterial infections compared with first-line antibiotics.

scholarly journals 695. Infective endocarditis in people who inject drugs (PWID) at UK Medical Center

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S399-S400
Author(s):  
Evelyn Villacorta Cari ◽  
John T Henderson ◽  
Donna R Burgess ◽  
J Zachary Porterfield ◽  
Nicole Leedy ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Tricuspid Valve ◽  
Bacterial Infections ◽  
Medical Center ◽  
Cross Sectional Study ◽  
Addiction Medicine ◽  
University Of Kentucky ◽  
Cross Sectional ◽  
Health Crisis ◽  
Gram Negative

Abstract Background The Intravenous Drug Use (IVDU) epidemic has been developing into a public health crisis in the last twenty years. As a result, the incidence of severe bacterial infections such as infective endocarditis (IE) has been rising dramatically. Methods Cross-sectional study, we reviewed records of all admissions to University of Kentucky hospitals with IVDU associated ICD9/10 codes who received an Infectious Diseases consult during 2018 and focused on the cases with a diagnosis of IE. We describe associated epidemiologic, clinical, and microbiological features Results We include 391 patients in this cohort, among those 157 patients were for IE. Patients had a median age of 34 years old (range: 20 - 62); 81 (51.5%) were female, and five (6.1%) were pregnant and 153 (97.4%) identified as white. A previous episode of infective endocarditis was reported in 55 (35%) cases. The most common illicit substances used were heroin 68 (43.3%) and methamphetamine 65 (41.45%). Tobacco abuse was reported in 134 (86.4%) cases. Fever reported in 93 (59.8%) cases, shortness of air in 43 (28.0%) cases, and chest pain in 44 (28.6%) cases were the most common symptoms. Hepatitis C antibody was positive in 115/149 (73.2%) and 3/143 (1.9%) were HIV positive. Right-sided IE was more frequent, the tricuspid valve was involved in 94 (59.8%) patients. Gram-positive pathogens were isolated in 139 (88.5%) patients, Staphylococcus aureus was isolated in 102 (64.9%) patients, of which 67 (65.7%) were methicillin resistant. Gram-negative pathogens were isolated in 18 (11.2%) patients. Eighty-eight (56.4%) patients had an addiction medicine consult during their admission, (22.9%) patients left against medical advice and 20 (12.7%) patients needed to be readmitted within 30 days after discharge. Overall mortality was 12.7% and was significantly associated with infection by gram-negative pathogens (RR: 2.5; CI 95% 1.05 – 6.25, p=0.037). Conclusion Infectious endocarditis is a frequent complication in PWID which carries a high risk of mortality and often involves the tricuspid valve. The most common pathogen isolated was S. aureus, isolation of gram-negative pathogens was associated with increased mortality. Disclosures All Authors: No reported disclosures

scholarly journals Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

2016 ◽  
Vol 48 (3) ◽  
pp. 181 ◽  
Author(s):  
Joon Hee Lee ◽  
Seul-Ki Kim ◽  
Seong Koo Kim ◽  
Seung Beom Han ◽  
Jae Wook Lee ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antibiotic Resistant ◽  
Gram Negative
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