scholarly journals Antibiotic killing of diversely generated populations of non-replicating bacteria

2018 ◽  
Author(s):  
Ingrid C McCall ◽  
Nilang Shah ◽  
Adithi Govindan ◽  
Fernando Baquero ◽  
Bruce R. Levin
Keyword(s):  
Bacterial Infections ◽  
Mechanisms Of Action ◽  
Gram Negative Bacteria ◽  
Common Belief ◽  
Peptide Antibiotics ◽  
Planktonic Bacteria ◽  
Identical Response ◽  
Short Course ◽  
Different Types ◽  
The Common

Non-replicating bacteria are known to be (or at least commonly thought to be) refractory to antibiotics to which they are genetically susceptible. Here, we explore the sensitivity to killing by bactericidal antibiotics of three classes of non-replicating populations of planktonic bacteria; (1) stationary phase, when the concentration of resources and/or nutrients are too low to allow for population growth; (2) persisters, minority subpopulations of susceptible bacteria surviving exposure to bactericidal antibiotics; (3) antibiotic-static cells, bacteria exposed to antibiotics that prevent their replication but kill them slowly if at all, the so-called bacteriostatic drugs. Using experimental populations of Staphylococcus aureus Newman and Escherichia coli K12 (MG1655) and respectively 9 and 7 different bactericidal antibiotics, we estimate the rates at which these drugs kill these different types of non-replicating bacteria. Contrary to the common belief that bacteria that are non-replicating are refractory to antibiotic-mediated killing, all three types of non-replicating populations of these Gram-positive and Gram-negative bacteria are consistently killed by aminoglycosides and the peptide antibiotics, daptomycin and colistin, respectively. This result indicates that non-replicating cells, irrespectively of why they do not replicate, have an almost identical response to bactericidal antibiotics. We discuss the implications of these results to our understanding of the mechanisms of action of antibiotics and the possibility of adding a short-course of aminoglycosides or peptide antibiotics to conventional therapy of bacterial infections.

scholarly journals Antibiotic Killing of Diversely Generated Populations of Nonreplicating Bacteria

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Ingrid C. McCall ◽  
Nilang Shah ◽  
Adithi Govindan ◽  
Fernando Baquero ◽  
Bruce R. Levin
Keyword(s):  
Bacterial Infections ◽  
Common Belief ◽  
Peptide Antibiotics ◽  
Content Type ◽  
Planktonic Bacteria ◽  
Identical Response ◽  
Short Course ◽  
Different Types ◽  
The Common ◽  
K 12

ABSTRACTNonreplicating bacteria are known to be (or at least commonly thought to be) refractory to antibiotics to which they are genetically susceptible. Here, we explore the sensitivity to killing by bactericidal antibiotics of three classes of nonreplicating populations of planktonic bacteria: (i) stationary phase, when the concentration of resources and/or nutrients are too low to allow for population growth; (ii) persisters, minority subpopulations of susceptible bacteria surviving exposure to bactericidal antibiotics; and (iii) antibiotic-static cells, bacteria exposed to antibiotics that prevent their replication but kill them slowly if at all, the so-called bacteriostatic drugs. Using experimental populations ofStaphylococcus aureusNewman andEscherichia coliK-12 (MG1655) and, respectively, nine and seven different bactericidal antibiotics, we estimated the rates at which these drugs kill these different types of nonreplicating bacteria. In contrast to the common belief that bacteria that are nonreplicating are refractory to antibiotic-mediated killing, all three types of nonreplicating populations of these Gram-positive and Gram-negative bacteria are consistently killed by aminoglycosides and the peptide antibiotics daptomycin and colistin, respectively. This result indicates that nonreplicating cells, irrespectively of why they do not replicate, have an almost identical response to bactericidal antibiotics. We discuss the implications of these results to our understanding of the mechanisms of action of antibiotics and the possibility of adding a short-course of aminoglycosides or peptide antibiotics to conventional therapy of bacterial infections.

scholarly journals On the Non-Gaussianity of the Height of Sea Waves

2021 ◽  
Vol 9 (12) ◽  
pp. 1446
Author(s):  
Alicia Nieto-Reyes
Keyword(s):  
Empirical Study ◽  
Gaussian Process ◽  
Random Projections ◽  
Common Belief ◽  
Sea Waves ◽  
One Dimensional ◽  
The Us ◽  
Different Types ◽  
The Common ◽  
Sea Wave

The objective of this paper is to prove that the sea wave height is not a Gaussian process. This is contrary to the common belief, as the height of a sea wave is generally considered a Gaussian process. With this aim in mind, an empirical study of the buoys along the US coast at a random day is pursued. The analysis differs from those in the literature in that we study the Gaussianity of the process as a whole and not just of its one-dimensional marginal. This is done by making use of random projections and a variety of tests that are powerful against different types of alternatives. The study has resulted in a rejection of the Gaussianity in over 96% of the studied cases.

Dual stain kit for the microscopic gram classification of ocular infection bacteria

1993 ◽  
Vol 51 ◽  
pp. 248-249
Author(s):  
Jacob S. Hanker ◽  
Dale N. Holdren ◽  
Kenneth L. Cohen ◽  
Beverly L. Giammara
Keyword(s):  
Contact Lenses ◽  
Ocular Infection ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Staining ◽  
Ocular Infections ◽  
Different Types ◽  
Culture Positive ◽  
Increased Susceptibility

Keratitis and conjunctivitis (infections of the cornea or conjunctiva) are ocular infections caused by various bacteria, fungi, viruses or parasites; bacteria, however, are usually prominent. Systemic conditions such as alcoholism, diabetes, debilitating disease, AIDS and immunosuppressive therapy can lead to increased susceptibility but trauma and contact lens use are very important factors. Gram-negative bacteria are most frequently cultured in these situations and Pseudomonas aeruginosa is most usually isolated from culture-positive ulcers of patients using contact lenses. Smears for staining can be obtained with a special swab or spatula and Gram staining frequently guides choice of a therapeutic rinse prior to the report of the culture results upon which specific antibiotic therapy is based. In some cases staining of the direct smear may be diagnostic in situations where the culture will not grow. In these cases different types of stains occasionally assist in guiding therapy.

Carbazole Derivatives as Kinase-Targeting Inhibitors for Cancer Treatment

2020 ◽  
Vol 20 (6) ◽  
pp. 444-465 ◽  
Author(s):  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
Alexia Barbarossa ◽  
Anna Caruso ◽  
Fedora Grande ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Mechanisms Of Action ◽  
Biological Pathways ◽  
G Protein Coupled Receptors ◽  
Ability To Act ◽  
Different Types ◽  
Activity Of Enzymes ◽  
Intercalating Agents ◽  
G Protein Coupled

Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.

Anticancer Properties of Essential Oils: An Overview

2018 ◽  
Vol 18 (10) ◽  
pp. 957-966 ◽  
Author(s):  
Milene Aparecida Andrade ◽  
Mariana Aparecida Braga ◽  
Pedro Henrique Souza Cesar ◽  
Marcus Vinicius Cardoso Trento ◽  
Mariana Araújo Espósito ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Essential Oils ◽  
Public Health Problem ◽  
Mechanisms Of Action ◽  
Low Molecular Weight ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Different Types ◽  
Antitumor Properties ◽  
Pharmaceutical Properties

Background: Essential oils are complex mixtures of low molecular weight compounds extracted from plants. Their main constituents are terpenes and phenylpropanoids, which are responsible for their biological and pharmaceutical properties, such as insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Cancer is a complex genetic disease considered as a serious public health problem worldwide, accounting for more than 8 million deaths annually. Objective: The activities of prevention and treatment of different types of cancer and the medicinal potential of essential oils are addressed in this review. Conclusion: Several studies have demonstrated anti-carcinogenic and antitumor activity for many essential oils obtained from various plant species. They may be used as a substitution to or in addition to conventional anti-cancer therapy. Although many studies report possible mechanisms of action for essential oils compounds, more studies are necessary in order to apply them safely and appropriately in cancer therapy.

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.

Aristotle on the Sources of the Ethical Life

2019 ◽  
Author(s):  
Sylvia Berryman
Keyword(s):  
Virtue Ethics ◽  
Human Nature ◽  
Common Belief ◽  
Ethical Life ◽  
Metaphysical Grounding ◽  
Middle Way ◽  
The Common

This work challenges the common belief that Aristotle’s virtue ethics is founded on an appeal to human nature, an appeal that is thought to be intended to provide both substantive ethical advice and justification for the demands of ethics. It is argued that it is not Aristotle’s intent, but the view is resisted that Aristotle was blind to questions of the source or justification of his ethical views. Aristotle’s views are interpreted as a ‘middle way’ between the metaphysical grounding offered by Platonists and the scepticism or subjectivist alternatives articulated by others. The commitments implicit in the nature of action figure prominently in this account: Aristotle reinterprets Socrates’ famous paradox that no one does evil willingly, taking it to mean that a commitment to pursuing the good is implicit in the very nature of action. This approach is compared to constructivism in contemporary ethics.

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.

scholarly journals Understanding Urban Commercial Vehicle Driver Behaviors and Decision Making

2021 ◽  
pp. 036119812110035
Author(s):  
Giacomo Dalla Chiara ◽  
Klaas Fiete Krutein ◽  
Andisheh Ranjbari ◽  
Anne Goodchild
Keyword(s):  
Commercial Vehicle ◽  
Operating Time ◽  
Common Belief ◽  
Policy Makers ◽  
Factors Affecting ◽  
Urban Freight ◽  
The Road ◽  
Commercial Drivers ◽  
The Common ◽  
Printed Materials

As e-commerce and urban deliveries spike, cities grapple with managing urban freight more actively. To manage urban deliveries effectively, city planners and policy makers need to better understand driver behaviors and the challenges they experience in making deliveries. In this study, we collected data on commercial vehicle (CV) driver behaviors by performing ridealongs with various logistics carriers. Ridealongs were performed in Seattle, Washington, covering a range of vehicles (cars, vans, and trucks), goods (parcels, mail, beverages, and printed materials), and customer types (residential, office, large and small retail). Observers collected qualitative observations and quantitative data on trip and dwell times, while also tracking vehicles with global positioning system devices. The results showed that, on average, urban CVs spent 80% of their daily operating time parked. The study also found that, unlike the common belief, drivers (especially those operating heavier vehicles) parked in authorized parking locations, with only less than 5% of stops occurring in the travel lane. Dwell times associated with authorized parking locations were significantly longer than those of other parking locations, and mail and heavy goods deliveries generally had longer dwell times. We also identified three main criteria CV drivers used for choosing a parking location: avoiding unsafe maneuvers, minimizing conflicts with other users of the road, and competition with other commercial drivers. The results provide estimates for trip times, dwell times, and parking choice types, as well as insights into why those decisions are made and the factors affecting driver choices.

Further Investigation upon the Water Movements in the English Channel. Drift-Bottle Experiments in the Summers of 1927, 1928 and 1929, with Critical Notes on Drift-Bottle Experiments in General.

1930 ◽  
Vol 17 (1) ◽  
pp. 241-275 ◽  
Author(s):  
J. N. Carruthers
Keyword(s):  
Wind Speed ◽  
North Sea ◽  
English Channel ◽  
The North ◽  
Different Types ◽  
The North Sea ◽  
The Common ◽  
Relationship Of ◽  
Great Simplicity ◽  
Simple Surface

In July–August of three different years common surface-floating bottles were set adrift at International Station E2 (49° 27' N.—4° 42' W.). With them, various types of drag-fitted bottles were also put out. The journeys accomplished are discussed, and the striking differences as between year and year in the case of the common surface floaters, and as between the different types in the same year, are commented upon in the light of the prevailing winds. An inter-relationship of great simplicity is deduced between wind speed and the rate of travel of simple surface floating bottles up-Channel and across the North Sea from the results of experiments carried out in four different summers.

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