scholarly journals A model-based approach to characterize enzyme-mediated response to antibiotic treatments: going beyond the SIR classification

2021 ◽  
Author(s):  
Virgile Andreani ◽  
Lingchong You ◽  
Philippe Glaser ◽  
Gregory Batt

To design appropriate treatments, one must be able to characterize accurately the response of bacteria to antibiotics. When exposed to β-lactam treatments, bacteria can be resistant and/or tolerant, and populations can exhibit resilience. Disentangling these phenomena is challenging and no consolidated understanding has been proposed so far. Because these responses involve processes happening at several levels, including the molecular level (e.g. antibiotic degradation), the cell physiology level (filamentation) and the population level (release of β-lactamases into the environment), quantitative modelling approaches are needed. Here, we propose a model of bacterial response to β-lactam treatments that accounts for bacterial resistance, tolerance, and population resilience. Our model can be calibrated solely based on optical density readouts, can predict the inoculum effect, and leads to a mechanistically relevant classification of bacterial response to treatments that goes beyond the classical susceptible / intermediate / resistant classification. Filamentation-mediated tolerance and collective enzyme-mediated antibiotic degradation are essential model features to explain the complex observed response of cell populations to antibiotic treatments.

Biosemiotics ◽  
2021 ◽  
Author(s):  
Adam Kłóś ◽  
Przemysław Mieszko Płonka

AbstractBacterial chemotaxis is often considered to be a textbook example of the rudimentary semiotic process. As such, it gives an excellent opportunity to better understand both semiosis and biology. Our study reviews this phenomenon in the light of up-to-date scientific knowledge to answer the most basic semiotic questions: what is the sign? What types of signs are there? What is the meaning understood on the molecular level, and by what means can it grow with time? As a case study, the bacterial chemotaxis toward glucose in E. coli species is chosen, and the semiotic framework of Charles Sanders Peirce applied. The analyses provide us with the following results: the sign, in its ultimate nature, is a general process. Bacterial chemotaxis can be understood in terms of Peircean type, symbol, and argument. The meaning on the molecular level is entirely pragmatic and, in this case, reduced to a bacterial response to glucose. A sign can grow through sign generalization, the emergence of different sign categories, the integration of these categories in functional cycles, and the introduction of contextuality. The sign of bacterial chemotaxis extends from the cell signaling pathways up to the population level. The presented results advance our knowledge of sign processing in the context of semiotic evolution.


2016 ◽  
Vol 9 ◽  
pp. CMAMD.S38531 ◽  
Author(s):  
Richard G. Crilly ◽  
Marita Kloseck ◽  
Selam Mequanint

Background We have previously reported a gender difference in the occurrence of hip fracture type with age in our local population. In the current report, we have explored this phenomenon in a Canadian population using five years of data from a national administrative database. We have compared community-dwelling and institutionalized individuals to determine if frailty is important and has a differential effect on the type of hip fracture experienced. Methods Hospitalization records from 2005 to 2009, in which the most responsible diagnosis, that is the diagnosis causing the admission to hospital, was a hip fracture, were obtained from the Discharge Abstract Database of the Canadian Institute for Health Information. Hip fracture type was identified using the Canadian Classification of Health Interventions and the International Classification of Diseases 10th Revision, Canada (ICD-10-CA). Hip fracture proportions were calculated for the study period and stratified by age group and sex. Results The relative proportion of intertrochanteric fractures in women rose from 35% in the youngest group (55–59 years) to 51% in the oldest group (84+ years; P < 0.0001). In men, the proportions remain relatively stable (47% and 44%, respectively). Community and institutionalized patients showed the same pattern. Conclusions The change in the proportion of the two hip fracture types that occur in women but not men may point to differences in the etiology and consequently the approaches to prevention for the two fracture types. Level of frailty did not seem to be important.


2020 ◽  
Vol 47 (3) ◽  
pp. 260
Author(s):  
J. Sean Doody ◽  
David Rhind ◽  
Simon Clulow

Abstract ContextThe invasive cane toad (Rhinella marina) has decimated populations of a keystone predator, the yellow-spotted monitor (Varanus panoptes), causing trophic cascades in Australian animal communities. Paradoxically, some V. panoptes populations coexist with toads. Demonstrating patterns in heterogeneous population-level impacts could reveal mechanisms that mediate individual effects, and provide managers with the ability to predict future impacts and assist in population recovery. AimsThe aim of the present study was to search for spatial patterns of population resilience of V. panoptes to invasive cane toads. MethodsPublished literature, unpublished data, reports and anecdotal information from trained herpetologists were used to test the emerging hypothesis that resilient predator populations are mainly coastal, whereas non-resilient populations are mostly inland. Key resultsPost-toad invasion data from 23 V. panoptes populations supported the idea that toad impacts on V. panoptes were heterogeneous; roughly half the populations could be designated as resilient (n=13) and half as non-resilient (n=10). Resilient populations had longer times since toad invasion than did non-resilient populations (39 versus 9 years respectively), supporting the idea that some recovery can occur. Non-resilient populations were exclusively inland (n=10), whereas resilient populations were split between inland (n=5) and coastal (n=8) populations. Resilient inland populations, however, were mainly confined to areas in which decades had passed since toad invasion. ConclusionsThe findings suggest that coastal V. panoptes populations fare much better than inland populations when it comes to surviving invading cane toads. ImplicationsUnambiguous recovery of monitor populations remains undemonstrated and will require long-term population monitoring before and after toad invasion.


2016 ◽  
Vol 51 (4) ◽  
pp. 309-316 ◽  
Author(s):  
Matthew S. Tenan

Few authors have reported nationally representative data on the number of sport and recreation (SR) injuries resulting in emergency department (ED) visitation. The existing studies have only provided 1 or 2 years of data and are not longitudinal in nature.Context: To use a novel algorithmic approach to determine if ED visitation is due to SR, resulting in a substantially larger longitudinal dataset.Objective: Descriptive epidemiology study.Design: Hospital.Setting: The National Hospital Ambulatory Medical Care Survey, a stratified random-sample survey of US hospital EDs was combined for years 1997–2009. There were 15 699 unweighted patient visits determined to be from SR.Patients or Other Participants: A custom algorithm classified SR visits based on the International Classification of Diseases, Ninth Revision, Clinical Modification E-code and pattern recognition of narrative text. Sport and recreation visits were assessed by age and categorized according to broad injury classifications. Additional quantification was performed on SR visits for lower extremity and knee-specific injuries. Sample weights were applied to provide national annual estimates.Main Outcome Measure(s): Annually, 4 243 000 ED visits resulted from SR. The largest classification of injury from SR was sprains and strains (896 000/y). Males had substantially more SR-related ED visits than females (2 929 000/y versus 1 314 000/y). For patients 10–49 years old, 1 093 000 lower extremity and 169 000 knee-specific injury visits annually were from SR. For both injury types, males had a higher rate of ED visitation; however, females had 25% and 39% greater odds of visitation for lower extremity and knee-specific injury, respectively.Results: The burden on the health system of ED visits from SR was substantial. Males presented in the ED at a higher rate for SR injury, though females had a higher proportion of lower extremity and knee-specific injury ED visitations from SR. This longitudinal analysis of population-level data provides the information to target research on specific subpopulations to mitigate SR injury.Conclusions:


2019 ◽  
Author(s):  
Jonas Bjork ◽  
Anton Nilsson ◽  
Carl Bonander ◽  
Ulf Strömberg

Abstract Background: Non-participation, losses to follow up and other types of study-specific selection mechanisms can be serious concerns in epidemiological studies. There are also selection processes that result in non-random groupings and changes in the composition of populations. These are continuously on-going irrespectively of whether they are subject to sampling in empirical studies. Such population selections are often overlooked, but may lead to lack of comparability of exposed and unexposed populations or decrease study validity in other ways. The overall aim of this study was to develop a simple but general framework for classifying various types of selection mechanisms of relevance for epidemiological research. Methods: We classify selection mechanisms in three dimensions: i) selection at the population level vs. selection that is study-specific, ii) type of mechanism (selection causing exposure vs. selection in population at risk), iii) timing of the selection (pre-exposure, during exposure or post-outcome). Results: Examples from the epidemiological literature of selection mechanisms are discussed and classified according to the three dimensions of the proposed framework. Conclusions: Increased mechanistic understanding of when, how, and why confusion of effects can occur because of selection is an important step towards improved validity of epidemiological research.


2021 ◽  
Author(s):  
Pierre Miasnikof ◽  
Vasily Giannakeas ◽  
Mireille Gomes ◽  
Lukasz Aleksandrowicz ◽  
Alexander Y. Shestopaloff ◽  
...  

Background Verbal autopsies (VA) are increasingly used in low- and middle-income countries where most causes of death (COD) occur at home without medical attention, and home deaths differ substantially from hospital deaths. Hence, there is no plausible “standard” against which VAs for home deaths may be validated. Previous studies have shown contradictory performance of automated methods compared to physician-based classification of CODs. We sought to compare the performance of the classic naive Bayes classifier (NBC) versus existing automated classifiers, using physician-based classification as the reference. Methods We compared the performance of NBC, an open-source Tariff Method (OTM), and InterVA-4 on three datasets covering about 21,000 child and adult deaths: the ongoing Million Death Study in India, and health and demographic surveillance sites in Agincourt, South Africa and Matlab, Bangladesh. We applied several training and testing splits of the data to quantify the sensitivity and specificity compared to physician coding for individual CODs and to test the cause-specific mortality fractions at the population level. Results The NBC achieved comparable sensitivity (median 0.51, range 0.48-0.58) to OTM (median 0.50, range 0.41-0.51), with InterVA-4 having lower sensitivity (median 0.43, range 0.36-0.47) in all three datasets, across all CODs. Consistency of CODs was comparable for NBC and InterVA-4 but lower for OTM. NBC and OTM achieved better performance when using a local rather than a non-local training dataset. At the population level, NBC scored the highest cause-specific mortality fraction accuracy across the datasets (median 0.88, range 0.87-0.93), followed by InterVA-4 (median 0.66, range 0.62-0.73) and OTM (median 0.57, range 0.42-0.58). Conclusions NBC outperforms current similar COD classifiers at the population level. Nevertheless, no current automated classifier adequately replicates physician classification for individual CODs. There is a need for further research on automated classifiers using local training and test data in diverse settings prior to recommending any replacement of physician-based classification of verbal autopsies.


2020 ◽  
Author(s):  
Jonas Bjork ◽  
Anton Nilsson ◽  
Carl Bonander ◽  
Ulf Strömberg

Abstract Background: Selection and selection bias are terms that lack consistent definitions and have varying meaning and usage across disciplines. There is also confusion in current definitions between underlying mechanisms that lead to selection and their consequences. Consequences of selection on study validity must be judged on a case-by-case basis depending on research question, study design and analytical decisions. The overall aim of the study was to develop a simple but general framework for classifying various types of selection processes of relevance for epidemiological research. Methods: Several original articles from the epidemiological literature and from related areas of observational research were reviewed in search of examples of selection processes, used terminology and description of the underlying mechanisms. Results: We classified the identified selection processes in three dimensions: i) selection level (selection at the population level vs. study-specific selection), ii) type of mechanism (selection in exposure vs. selection in population composition), iii) timing of the selection (at exposure entry, during exposure or post-outcome). Conclusions: Increased understanding of when, how, and why selection occur is an important step towards improved validity of epidemiological research.


2007 ◽  
Vol 57 (12) ◽  
pp. 2894-2901 ◽  
Author(s):  
J. M. Young ◽  
D.-C. Park

The relationships of the genus Azotobacter, Azomonas macrocytogenes and the genus Pseudomonas were revealed by comparative analysis of partial 16S rRNA and atpD, carA and recA gene sequences and as concatenated nucleotide and peptide sequences. Sequence similarities of Azotobacter species and Azomonas macrocytogenes indicated that these may be considered to be synonyms at the molecular level. In addition, these species show an intimate relationship with species of Pseudomonas, especially P. aeruginosa (the type species of the genus). In terms of the current circumscription of the genus Pseudomonas, Azotobacter and Azomonas macrocytogenes should be considered for amalgamation with Pseudomonas. Azotobacter and Azomonas comprise nitrogen-fixing strains with large pleomorphic cells that form cysts, and peritrichous flagella insertion; characteristics not included in the current circumscription of Pseudomonas. The data are discussed in the light of whether lateral transfer of genes could be involved in the determination of significant morphological characteristics, thus leading to a problem that may be encountered more frequently: how to resolve classification of taxa based on conserved sequences with those based on their phenotype. More fundamentally, the results illuminate problems that will increasingly be encountered: by what criteria can taxa be delineated, what are the most appropriate methods for classification, and what are the proper assumptions of bacterial classification?


2011 ◽  
Vol 8 (4) ◽  
pp. 6833-6857
Author(s):  
S. A. Krug ◽  
S. L. Eggers ◽  
B. Matthiessen

Abstract. The ongoing rise in atmospheric pCO2 and the consequent increase in ocean acidification have direct effects on marine calcifying phytoplankton which potentially translates into altered carbon export. To date it remains unclear first, how nutrient ratio, in particular from coccolithophores preferred phosphate limitation, interacts with pCO2 on particulate carbon accumulation. Second, how direct physiological responses on the cellular level translate into a net population response. In this study cultures of Emiliania huxleyi were full-factorially exposed to two different N:P ratios (Redfield and high N:P) and three different pCO2 levels. Effects on net population particulate inorganic and organic carbon (PIC, POC) were measured after E. huxleyi cultures reached stationary phase. Thereby cell sizes and total cell abundance were taken into account. Corresponding to literature results show a significant negative cellular PIC and POC response which, however, was strongest under high N:P ratio. In contrast, net population PIC and POC accumulation was significantly attenuated under high N:P ratio. We suggest that less cellular nutrient accumulation allowed for higher cell abundances which compensated for the strong negative cellular PIC and POC response to pCO2 on the population level. Moreover, the design of this study also allowed following natural alteration of carbon chemistry through changing DIC and alkalinity. Our results suggest that at high initial pCO2 natural alteration of pCO2 during the experimental runtime was regulated by algal biomass. In contrast, at low initial pCO2 the PIC/POC ratio was responsible for changes in pCO2. Our results point to the fact that the physiological (i.e. cellular) PIC and POC response to ocean acidification cannot be linearly extrapolated to total population response and thus carbon export. It is therefore recommended to consider effects of nutrient limitation on cell physiology and translate these to net population carbon accumulation when predicting the influence of coccolithophores on both, the atmospheric pCO2 feedback and their function in carbon export mechanisms.


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