scholarly journals Many Means to a Common End: the Intricacies of (p)ppGpp Metabolism and Its Control of Bacterial Homeostasis

2015 ◽  
Vol 197 (7) ◽  
pp. 1146-1156 ◽  
Author(s):  
Anthony O. Gaca ◽  
Cristina Colomer-Winter ◽  
José A. Lemos
Keyword(s):  
Bacterial Species ◽  
Cell Formation ◽  
Stringent Response ◽  
Survival Strategies ◽  
Cell Physiology ◽  
Bacterial Survival ◽  
Stress Survival ◽  
Rapid Accumulation ◽  
Relationship Of

In nearly all bacterial species examined so far, amino acid starvation triggers the rapid accumulation of the nucleotide second messenger (p)ppGpp, the effector of the stringent response. While for years the enzymes involved in (p)ppGpp metabolism and the significance of (p)ppGpp accumulation to stress survival were considered well defined, a recent surge of interest in the field has uncovered an unanticipated level of diversity in how bacteria metabolize and utilize (p)ppGpp to rapidly synchronize a variety of biological processes important for growth and stress survival. In addition to the classic activation of the stringent response, it has become evident that (p)ppGpp exerts differential effects on cell physiology in an incremental manner rather than simply acting as a biphasic switch that controls growth or stasis. Of particular interest is the intimate relationship of (p)ppGpp with persister cell formation and virulence, which has spurred the pursuit of (p)ppGpp inhibitors as a means to control recalcitrant infections. Here, we present an overview of the enzymes responsible for (p)ppGpp metabolism, elaborate on the intricacies that link basal production of (p)ppGpp to bacterial homeostasis, and discuss the implications of targeting (p)ppGpp synthesis as a means to disrupt long-term bacterial survival strategies.

scholarly journals Targeting the Mycobacterium tuberculosis Stringent Response as a Strategy for Shortening Tuberculosis Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Carina Danchik ◽  
Siqing Wang ◽  
Petros C. Karakousis
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Species ◽  
Stringent Response ◽  
Therapeutic Benefit ◽  
Current Understanding ◽  
Antibiotic Tolerance ◽  
Bacterial Survival ◽  
Inorganic Polyphosphate ◽  
Regulatory Molecule ◽  
Response To Stress

The stringent response is well conserved across bacterial species and is a key pathway involved both in bacterial survival and virulence and in the induction of antibiotic tolerance in Mycobacteria. It is mediated by the alarmone (p)ppGpp and the regulatory molecule inorganic polyphosphate in response to stress conditions such as nutrient starvation. Efforts to pharmacologically target various components of the stringent response have shown promise in modulating mycobacterial virulence and antibiotic tolerance. In this review, we summarize the current understanding of the stringent response and its role in virulence and tolerance in Mycobacteria, including evidence that targeting this pathway could have therapeutic benefit.

scholarly journals Adaptations Accumulated under Prolonged Resource Exhaustion Are Highly Transient

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Sarit Avrani ◽  
Sophia Katz ◽  
Ruth Hershberg
Keyword(s):  
Bacterial Species ◽  
Growth Media ◽  
Bacterial Survival ◽  
Content Type ◽  
Prolonged Starvation ◽  
E Coli ◽  
Resource Exhaustion ◽  
Shed Light ◽  
External Growth

ABSTRACT Many nonsporulating bacterial species can survive for years within exhausted growth media in a state termed long-term stationary phase (LTSP). We have been carrying out evolutionary experiments aimed at elucidating the dynamics of genetic adaptation under LTSP. We showed that Escherichia coli adapts to prolonged resource exhaustion through the highly convergent acquisition of mutations. In the most striking example of such convergent adaptation, we observed that across all independently evolving LTSP populations, over 90% of E. coli cells carry mutations to one of three specific sites of the RNA polymerase core enzyme (RNAPC). These LTSP adaptations reduce the ability of the cells carrying them to grow once fresh resources are again provided. Here, we examine how LTSP populations recover from costs associated with their adaptation once resources are again provided to them. We demonstrate that due to the ability of LTSP populations to maintain high levels of standing genetic variation during adaptation, costly adaptations are very rapidly purged from the population once they are provided with fresh resources. We further demonstrate that recovery from costs acquired during adaptation under LTSP occurs more rapidly than would be possible if LTSP adaptations had fixed during the time populations spent under resource exhaustion. Finally, we previously reported that under LTSP, some clones develop a mutator phenotype, greatly increasing their mutation accumulation rates. Here, we show that the mechanisms by which populations recover from costs associated with fixed adaptations may depend on mutator status. IMPORTANCE Many bacterial species can survive for decades under starvation, following the exhaustion of external growth resources. We have previously shown that bacteria genetically adapt under these conditions in a manner that reduces their ability to grow once resources again become available. Here, we study how populations that have been subject to very prolonged resource exhaustion recover from costs associated with their adaptation. We demonstrate that rapid adaptations acquired under prolonged starvation tend to be highly transient, rapidly reducing in frequency once bacteria are no longer starved. Our results shed light on the longer-term consequences of bacterial survival under prolonged starvation. More generally, these results may also be applicable to understanding longer-term consequences of rapid adaptation to additional conditions as well.

scholarly journals Fatty acid starvation activates RelA by depleting lysine precursor pyruvate

2019 ◽  
Author(s):  
Anurag Kumar Sinha ◽  
Kristoffer Skovbo Winther ◽  
Mohammad Roghanian ◽  
Kenn Gerdes
Keyword(s):  
Fatty Acid ◽  
Slow Growth ◽  
Stringent Response ◽  
Fold Increase ◽  
Underlying Mechanism ◽  
Cell Physiology ◽  
Nutrient Depletion ◽  
Stress Survival ◽  
Secondary Messengers ◽  
Rapid Activation

SummaryBacteria experiencing nutrient starvation induce the ubiquitous stringent response, a profound physiological change that reprograms cell physiology from fast to slow growth and stress survival. The stringent response is mediated by the secondary messengers pppGpp and ppGpp collectively referred to as (p)ppGpp or “alarmone”. InEscherichia coli, two paralogs, RelA and SpoT, synthesize (p)ppGpp. RelA is activated by amino acid starvation whereas SpoT, which can also degrade (p)ppGpp, responds to fatty acid (FA), carbon and phosphate starvation. Here, we discover that FA starvation leads to rapid activation of RelA and reveal the underlying mechanism. We show that fatty acid starvation leads to depletion of lysine that, in turn, leads to the accumulation of uncharged tRNAlysand activation of RelA. SpoT was also activated by fatty acid starvation but to a lower level and with a delayed kinetics. Next, we discovered that pyruvate, a precursor of lysine, is depleted by FA starvation. We also propose a mechanism that explains how FA starvation leads to pyruvate depletion. Together our results indicate that many responses to nutrient depletion may ultimately result indirectly from depletion of amino acids and thereby activating RelA. Interestingly, FA starvation provoked a ~100-fold increase inrelAdependent ampicillin tolerance.

scholarly journals Survival of the Fittest: The Relationship of (p)ppGpp With Bacterial Virulence

2020 ◽  
Vol 11 ◽  
Author(s):  
Shivani Kundra ◽  
Cristina Colomer-Winter ◽  
José A. Lemos
Keyword(s):  
Stringent Response ◽  
Intimate Relationship ◽  
Bacterial Virulence ◽  
Cell Physiology ◽  
The Past ◽  
The Subject ◽  
Relationship Of ◽  
The Relationship ◽  
Survival Of The Fittest

The signaling nucleotide (p)ppGpp has been the subject of intense research in the past two decades. Initially discovered as the effector molecule of the stringent response, a bacterial stress response that reprograms cell physiology during amino acid starvation, follow-up studies indicated that many effects of (p)ppGpp on cell physiology occur at levels that are lower than those needed to fully activate the stringent response, and that the repertoire of enzymes involved in (p)ppGpp metabolism is more diverse than initially thought. Of particular interest, (p)ppGpp regulation has been consistently linked to bacterial persistence and virulence, such that the scientific pursuit to discover molecules that interfere with (p)ppGpp signaling as a way to develop new antimicrobials has grown substantially in recent years. Here, we highlight contemporary studies that have further supported the intimate relationship of (p)ppGpp with bacterial virulence and studies that provided new insights into the different mechanisms by which (p)ppGpp modulates bacterial virulence.

scholarly journals Domain randomization-enhanced deep learning models for bird detection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Mao ◽  
Jun Kang Chow ◽  
Pin Siang Tan ◽  
Kuan-fu Liu ◽  
Jimmy Wu ◽  
...  
Keyword(s):  
Deep Learning ◽  
Continuous Monitoring ◽  
Bird Species ◽  
Training Data ◽  
Learning Models ◽  
Fine Grained ◽  
Bird Detection ◽  
Relationship Of ◽  
The Relationship

AbstractAutomatic bird detection in ornithological analyses is limited by the accuracy of existing models, due to the lack of training data and the difficulties in extracting the fine-grained features required to distinguish bird species. Here we apply the domain randomization strategy to enhance the accuracy of the deep learning models in bird detection. Trained with virtual birds of sufficient variations in different environments, the model tends to focus on the fine-grained features of birds and achieves higher accuracies. Based on the 100 terabytes of 2-month continuous monitoring data of egrets, our results cover the findings using conventional manual observations, e.g., vertical stratification of egrets according to body size, and also open up opportunities of long-term bird surveys requiring intensive monitoring that is impractical using conventional methods, e.g., the weather influences on egrets, and the relationship of the migration schedules between the great egrets and little egrets.

scholarly journals Non-Local and Multi-Scale Mechanisms for Image Inpainting

Sensors ◽  
2021 ◽  
Vol 21 (9) ◽  
pp. 3281
Author(s):  
Xu He ◽  
Yong Yin
Keyword(s):  
Markov Random Fields ◽  
Receptive Fields ◽  
Image Inpainting ◽  
Long Distance ◽  
Visual Appearance ◽  
Fine Grained ◽  
Multi Scale ◽  
Non Local ◽  
Relationship Of

Recently, deep learning-based techniques have shown great power in image inpainting especially dealing with squared holes. However, they fail to generate plausible results inside the missing regions for irregular and large holes as there is a lack of understanding between missing regions and existing counterparts. To overcome this limitation, we combine two non-local mechanisms including a contextual attention module (CAM) and an implicit diversified Markov random fields (ID-MRF) loss with a multi-scale architecture which uses several dense fusion blocks (DFB) based on the dense combination of dilated convolution to guide the generative network to restore discontinuous and continuous large masked areas. To prevent color discrepancies and grid-like artifacts, we apply the ID-MRF loss to improve the visual appearance by comparing similarities of long-distance feature patches. To further capture the long-term relationship of different regions in large missing regions, we introduce the CAM. Although CAM has the ability to create plausible results via reconstructing refined features, it depends on initial predicted results. Hence, we employ the DFB to obtain larger and more effective receptive fields, which benefits to predict more precise and fine-grained information for CAM. Extensive experiments on two widely-used datasets demonstrate that our proposed framework significantly outperforms the state-of-the-art approaches both in quantity and quality.

Technology and Employment in Developing Countries

1978 ◽  
Vol 16 (4) ◽  
pp. 549-564 ◽  
Author(s):  
J. W. Garmany
Keyword(s):  
Developing Countries ◽  
Optimum Combination ◽  
Current Consumption ◽  
The Creation ◽  
Relationship Of ◽  
The Relationship ◽  
Choice Of Technology

This article discusses some of the issues involved in the choice of technology in developing countries, especially those in Africa, and the relationship of this to employment and output. The problem is to find an optimum combination of productive resources that comes nearest to satisfying two objectives: the full and economically efficient utilisation of such resources, and the creation of as much surplus as possible over current consumption, thereby making possible new investment and long-term growth.

scholarly journals The Relationship between Reputation, Customer Satisfaction, Trust, and Loyalty

2014 ◽  
Vol 4 (3) ◽  
pp. 368 ◽  
Author(s):  
Roshana Gul
Keyword(s):  
Customer Satisfaction ◽  
Customer Loyalty ◽  
Significant Relationship ◽  
Positive Sign ◽  
Medical College ◽  
Independent Variable ◽  
Relationship Of ◽  
The Relationship ◽  
Self Administered Questionnaire

Though a lot of studies have been done to conclude customer loyalty as dependent variable but still there is a vast margin of researches to be conducted in future in different spheres of this construct. On the other hand the truth of the importance of customer loyalty as an enduring asset cannot be falsified. It is fundamental for organizations to build up long term and mutual beneficial associations with the customers. The purpose of this research paper is to show the inter relationship of reputation, customer satisfaction and trust on customer loyalty. According to the observations reputation is the major independent variable that has significant relationship with customer satisfaction, customer loyalty, and trust. Data for this research study was taken from the Islamia University, Quaid-e-Azam Medical College, and different banks located at various geographic locations of Bahawalpur region of Pakistan. Data was collected through self administered questionnaire and analyzed by using regression through SPSS. The results have been drawn from 150 users of NISHAT LINEN and it was found that there is positive and significant relationship among reputation, customer satisfaction, trust and customer loyalty. Hence the studies give the positive sign that with the increment of reputation, customer satisfaction and trust the customer loyalty enhances.  

The Research on the Strategies for Sustainable Development and Environmental Protection

2013 ◽  
Vol 869-870 ◽  
pp. 786-790
Author(s):  
Chen Chen Zhang
Keyword(s):  
Sustainable Development ◽  
Environmental Protection ◽  
Development Strategy ◽  
Protection Measures ◽  
The Sustainable Development ◽  
National Economic ◽  
History Of ◽  
Dialectical Relationship ◽  
Relationship Of

The strategies for sustainable development have been included in the medium and long term plan of 2010 for national economic and social development. Protecting the environment is the most important prerequisite and safeguards for the sustainable development strategy. In the study, we described the history of the environmental problems in the world, the proposal and implications of sustainable development, and outlined the dialectical relationship of development with the environment. The environmental protection measures for sustainable development were proposed here, according to the environmental situation severely affecting its biophysical environment.

scholarly journals Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure

2021 ◽  
Vol 22 (14) ◽  
pp. 7521
Author(s):  
Marko Nedeljković ◽  
Diego Emiliano Sastre ◽  
Eric John Sundberg
Keyword(s):  
Immune Responses ◽  
Basal Body ◽  
Vaccine Development ◽  
Bacterial Species ◽  
High Variability ◽  
Bacterial Survival ◽  
Bacterial Flagellum ◽  
Capping Proteins ◽  
Flagellar Filament ◽  
Flagellar Assembly

The bacterial flagellum is a complex and dynamic nanomachine that propels bacteria through liquids. It consists of a basal body, a hook, and a long filament. The flagellar filament is composed of thousands of copies of the protein flagellin (FliC) arranged helically and ending with a filament cap composed of an oligomer of the protein FliD. The overall structure of the filament core is preserved across bacterial species, while the outer domains exhibit high variability, and in some cases are even completely absent. Flagellar assembly is a complex and energetically costly process triggered by environmental stimuli and, accordingly, highly regulated on transcriptional, translational and post-translational levels. Apart from its role in locomotion, the filament is critically important in several other aspects of bacterial survival, reproduction and pathogenicity, such as adhesion to surfaces, secretion of virulence factors and formation of biofilms. Additionally, due to its ability to provoke potent immune responses, flagellins have a role as adjuvants in vaccine development. In this review, we summarize the latest knowledge on the structure of flagellins, capping proteins and filaments, as well as their regulation and role during the colonization and infection of the host.

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