Epigenetic memories and the evolution of infectious diseases

AbstractGenes with identical DNA sequence may show differential expression because of epigenetic marks. Where epigenetic marks respond to past conditions, they represent a form of “memory”. Despite their medical relevance, the impact of memories on the evolution of infectious diseases has rarely been considered. Here we explore the evolution of virulence in pathogens that carry memories of the sex of their previous host. We show that this form of memory provides information about the sex of present and future hosts when the sexes differ in their pathogen’s transmission pattern. Memories of past hosts enable the evolution of greater virulence in infections originating from one sex and infections transmitted across sexes. Thus, our results account for patterns of virulence that have, to date, defied medical explanation. In particular, it has been observed that girls infected by boys (or boys infected by girls) are more likely to die from measles, chickenpox and polio than girls infected by girls (or boys infected by boys). We also evaluate epigenetic therapies that tamper with the memories of infecting pathogens. More broadly, our findings imply that pathogens can be selected to carry memories of past environments other than sex. This identifies new directions in personalised medicine.

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Epigenetic inheritance and the evolution of infectious diseases

10.1101/2020.08.29.273326 ◽

2020 ◽

Author(s):

David V. McLeod ◽

Geoff Wild ◽

Francisco Úbeda

Keyword(s):

Natural Selection ◽

Infectious Diseases ◽

Dna Sequences ◽

Personalised Medicine ◽

Epigenetic Inheritance ◽

Social Differences ◽

Epigenetic Marks ◽

Evolution Of Virulence ◽

The Impact ◽

Past Conditions

AbstractGenes with identical DNA sequences may show differential expression because of epigenetic marks. These marks in pathogens are key to their virulence and are being evaluated as targets for medical treatment. Where epigenetic marks were created in response to past conditions (epigenetically inherited), they represent a form of memory, the impact of which has not been considered in the evolution of infectious diseases. We fill this gap by exploring the evolution of virulence in pathogens that inherit epigenetic information on the sex of their previous host. We show that memories of past hosts can also provide clues about the sex of present and future hosts when women and men differ in their immunity to infection and/or their interactions with the sexes. These biological and social differences between the sexes are pervasive in humans. We show that natural selection can favour the evolution of greater virulence in infections originating from one sex. Furthermore, natural selection can favour the evolution of greater virulence in infections across sexes (or within sexes). Our results explain certain patterns of virulence in diseases like measles, chickenpox and polio that have puzzled medical researchers for decades. In particular, they address why girls infected by boys (or boys infected by girls) are more likely to die from the infection than girls infected by girls (or boys infected by boys). We propose epigenetic therapies to treat infections by tampering with the memories of infecting pathogens. Counterintuitively, we predict that successful therapies should target pathogen’s genes that inhibit virulence, rather than those enhancing virulence. Our findings imply that pathogens can carry memories of past environments other than sex (e.g. those related to socioeconomic status) that may condition their virulence and could signify an important new direction in personalised medicine.

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mSphere of Influence: Translating Gut Microbiome Studies To Benefit Human Health

mSphere ◽

10.1128/msphere.00592-20 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Anna M. Seekatz

Keyword(s):

Sequence Analysis ◽

Infectious Diseases ◽

Gut Microbiota ◽

Dna Sequence ◽

High Throughput ◽

Gut Microbiome ◽

Monozygotic Twins ◽

Fermented Milk ◽

Gnotobiotic Mice ◽

The Impact

ABSTRACT Anna M. Seekatz works in the field of the gut microbiome as it related to infectious diseases. In this “mSphere of Influence” article, she reflects on how two studies, “The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins” (N. P. McNulty, T. Yatsunenko, A. Hsiao, et al., Sci Transl Med 3:106ra106, 2011) and “High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria” (M. J. Hamilton, A. R. Weingarden, T. Unno, A. Khoruts, and M. J. Sadowsky, Gut Microbes 4:125–135, 2013), shaped how she approaches interpreting microbiome studies.

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Awareness of symptomatic differences Covid-19, SARS, Swine Flu, Common cold among dental students

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3431 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 1026-1033

Author(s):

Nivedha Valliammai Mahalingam ◽

Abilasha R ◽

Kavitha S

Keyword(s):

Infectious Diseases ◽

Undergraduate Students ◽

Common Cold ◽

Emerging Infectious Diseases ◽

Dental Students ◽

Swine Flu ◽

Viral Diseases ◽

Surveillance Systems ◽

Cross Sectional ◽

The Impact

Enormous successes have been obtained against the control of major epidemic diseases, such as SARS, MERS, Ebola, Swine Flu in the past. Dynamic interplay of biological, socio-cultural and ecological factors, together with novel aspects of human-animal interphase, pose additional challenges with respect to the emergence of infectious diseases. The important challenges faced in the control and prevention of emerging and re-emerging infectious diseases range from understanding the impact of factors that are necessary for the emergence, to development of strengthened surveillance systems that can mitigate human suffering and death. The aim of the current study is to assess the awareness of symptomatic differences between viral diseases like COVID-19, SARS, Swine flu and common cold among dental students that support the prevention of emergence or re-emergence. Cross-sectional type of study conducted among the undergraduate students comprising 100 Subjects. A questionnaire comprising 15 questions in total were framed, and responses were collected in Google forms in SPSS Software statistical analysis. The study has concluded that dental students have an awareness of the symptomatic differences between infectious viral disease. The study concluded that the awareness of symptomatic differences between viral diseases like COVID-19, SARS, Swine flu, Common cold is good among the dental students who would pave the way for early diagnosis and avoid spreading of such diseases. A further awareness can be created by regular webinars, seminars and brainstorming sessions among these healthcare professionals.

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PODC 2020 Review

ACM SIGACT News ◽

10.1145/3444815.3444827 ◽

2021 ◽

Vol 51 (4) ◽

pp. 75-81

Author(s):

Ahad Mirza Baig ◽

Alkida Balliu ◽

Peter Davies ◽

Michal Dory

Keyword(s):

Machine Learning ◽

Distributed Computing ◽

Keynote Speaker ◽

Lively Discussion ◽

Theoretical Understanding ◽

New Directions ◽

New Ideas ◽

New Challenges ◽

The Impact ◽

Distributed Machine Learning

Rachid Guerraoui was the rst keynote speaker, and he got things o to a great start by discussing the broad relevance of the research done in our community relative to both industry and academia. He rst argued that, in some sense, the fact that distributed computing is so pervasive nowadays could end up sti ing progress in our community by inducing people to work on marginal problems, and becoming isolated. His rst suggestion was to try to understand and incorporate new ideas coming from applied elds into our research, and argued that this has been historically very successful. He illustrated this point via the distributed payment problem, which appears in the context of blockchains, in particular Bitcoin, but then turned out to be very theoretically interesting; furthermore, the theoretical understanding of the problem inspired new practical protocols. He then went further to discuss new directions in distributed computing, such as the COVID tracing problem, and new challenges in Byzantine-resilient distributed machine learning. Another source of innovation Rachid suggested was hardware innovations, which he illustrated with work studying the impact of RDMA-based primitives on fundamental problems in distributed computing. The talk concluded with a very lively discussion.

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Evaluation of Clinical Outcomes after Introduction of a Dedicated Infectious Diseases- Critical Care Medicine Service in Critical Care Units

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab182 ◽

2021 ◽

Author(s):

Polina Trachuk ◽

Vagish Hemmige ◽

Ruth Eisenberg ◽

Kelsie Cowman ◽

Victor Chen ◽

...

Keyword(s):

Critical Care ◽

Infectious Diseases ◽

Clinical Outcomes ◽

Broad Spectrum ◽

Critical Care Medicine ◽

Care Hospital ◽

Intervention Period ◽

Broad Spectrum Antibiotics ◽

Antibiotic Utilization ◽

The Impact

Abstract Objective Infection is a leading cause of admission to intensive care units (ICU), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID-Critical Care Medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. Method In this single site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during post-intervention period from January 1, 2017 to December 31, 2017 and compared it to antibiotic utilization in the same ICUs during the pre-intervention period from January 1, 2015 to December 31, 2015. Results Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam and cefepime during the intervention period. When compared to pre-intervention period there was no difference in-hospital mortality, hospital length of stay and re-admission. Conclusion With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.

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The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study

BMC Infectious Diseases ◽

10.1186/s12879-021-06372-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fabian Chiong ◽

Mohammed S. Wasef ◽

Kwee Chin Liew ◽

Raquel Cowan ◽

Danny Tsai ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Infectious Diseases ◽

Retrospective Cohort ◽

Source Control ◽

First Episode ◽

Oral Antibiotic ◽

Genotypic Analysis ◽

Infectious Diseases Consultation ◽

Staphylococcal Aureus ◽

The Impact

Abstract Background Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB. Methods This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality. Results A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95–20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups. Conclusion Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.

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Chromatin Manipulation and Editing: Challenges, New Technologies and Their Use in Plants

International Journal of Molecular Sciences ◽

10.3390/ijms22020512 ◽

2021 ◽

Vol 22 (2) ◽

pp. 512

Author(s):

Kateryna Fal ◽

Denisa Tomkova ◽

Gilles Vachon ◽

Marie-Edith Chabouté ◽

Alexandre Berr ◽

...

Keyword(s):

Cell Fate ◽

Dna Sequence ◽

Zinc Finger ◽

Chromatin Structure ◽

New Technologies ◽

Dna Interaction ◽

The Other ◽

Proof Of Concept ◽

Epigenetic Marks ◽

Molecular Events

An ongoing challenge in functional epigenomics is to develop tools for precise manipulation of epigenetic marks. These tools would allow moving from correlation-based to causal-based findings, a necessary step to reach conclusions on mechanistic principles. In this review, we describe and discuss the advantages and limits of tools and technologies developed to impact epigenetic marks, and which could be employed to study their direct effect on nuclear and chromatin structure, on transcription, and their further genuine role in plant cell fate and development. On one hand, epigenome-wide approaches include drug inhibitors for chromatin modifiers or readers, nanobodies against histone marks or lines expressing modified histones or mutant chromatin effectors. On the other hand, locus-specific approaches consist in targeting precise regions on the chromatin, with engineered proteins able to modify epigenetic marks. Early systems use effectors in fusion with protein domains that recognize a specific DNA sequence (Zinc Finger or TALEs), while the more recent dCas9 approach operates through RNA-DNA interaction, thereby providing more flexibility and modularity for tool designs. Current developments of “second generation”, chimeric dCas9 systems, aiming at better targeting efficiency and modifier capacity have recently been tested in plants and provided promising results. Finally, recent proof-of-concept studies forecast even finer tools, such as inducible/switchable systems, that will allow temporal analyses of the molecular events that follow a change in a specific chromatin mark.

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Threshold Effects of Infectious Disease Outbreaks on Livestock Prices: Cases of African Swine Fever and Avian Influenza in South Korea

Applied Sciences ◽

10.3390/app11115114 ◽

2021 ◽

Vol 11 (11) ◽

pp. 5114

Author(s):

Hyung-Chul Rah ◽

Hyeon-Woong Kim ◽

Aziz Nasridinov ◽

Wan-Sup Cho ◽

Seo-Hwa Choi ◽

...

Keyword(s):

Avian Influenza ◽

Infectious Diseases ◽

Disease Outbreaks ◽

African Swine Fever ◽

Threshold Effect ◽

Impact Response ◽

Threshold Effects ◽

Infectious Disease Outbreaks ◽

Retail Prices ◽

The Impact

In this paper we demonstrate the threshold effects of infectious diseases on livestock prices. Daily retail prices of pork and chicken were used as structured data; news and SNS mentions of African Swine Fever (ASF) and Avian Influenza (AI) were used as unstructured data. Models were tested for the threshold effects of disease-related news and SNS frequencies, specifically those related to ASF and AI, on the retail prices of pork and chicken, respectively. The effects were found to exist, and the values of ASF-related news on pork prices were estimated to be −9 and 8, indicating that the threshold autoregressive (TAR) model can be divided into three regimes. The coefficients of the ASF-related SNS frequencies on pork prices were 1.1666, 0.2663 and −0.1035 for regimes 1, 2 and 3, respectively, suggesting that pork prices increased by 1.1666 Korean won in regime 1 when ASF-related SNS frequencies increased. To promote pork consumption by SNS posts, the required SNS frequencies were estimated to have impacts as great as one standard deviation in the pork price. These values were 247.057, 1309.158 and 2817.266 for regimes 1, 2 and 3, respectively. The impact response periods for pork prices were estimated to last 48, 6, and 8 days for regimes 1, 2 and 3, respectively. When the prediction accuracies of the TAR and autoregressive (AR) models with regard to pork prices were compared for the root mean square error, the prediction accuracy of the TAR model was found to be slightly better than that of the AR. When the threshold effect of AI-related news on chicken prices was tested, a linear relationship appeared without a threshold effect. These findings suggest that when infectious diseases such as ASF occur for the first time, the impact on livestock prices is significant, as indicated by the threshold effect and the long impact response period. Our findings also suggest that the impact on livestock prices is not remarkable when infectious diseases occur multiple times, as in the case of AI. To date, this study is the first to suggest the use of SNS to promote meat consumption.

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