Amylases and their importance during glycan degradation

Contributed by Narine Arabyan

Amylases catalyze the cleavage of α-D-1,4 and α-D-1,6-glycosidic bonds in starch and related carbohydrates. Amylases are widely distributed in nature and are important in carbohydrate metabolism. Amylases in Salmonella are poorly characterized glycosyl hydrolases. The importance of amylases during Salmonella infection is understudied, especially as new virulence factors. The genome of Salmonella Typhimurium LT2 contains four amylases that are classified under GH13 family: malS (periplasmic α-amylase), amyA (cytoplasmic α-amylase), glgX (glycogen debranching enzyme) and glgB (1,4-α-glucan branching enzyme). Although glgX and glgB are not annotated as amylases, both have a conserved α-amylase domain and function as amylases. Investigating the genomic diversity of microbial amylases will aid in understanding their importance during pathogenesis. Inhibitors of amylases can be new drug targets. Amylases play an important role by altering the host glycan profiles during infection to gain access of the host epithelial cells by binding to terminal mannose molecules to initiate glycan degradation (1). Weimer’s group also demonstrated that each of the four mutant amylase strains (ΔmalS, ΔamyA, ΔglgX, and ΔglgB) had different invasion phenotypes during the in vitro infection of differentiated colonic epithelial cells (Caco-2) (1); however only ΔmalS significantly (p<0.05) reduced adhesion and invasion during infection that were comparable to a non-pathogenic Salmonella strain (1).

  1. Arabyan N, Park D, Foutouhi S, Weis AM, Huang BC, Williams CC, Desai P, Shah J, Jeannotte R, Kong N, Lebrilla CB, Weimer BC. 2016. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep 6:29525.
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A New Take on the Dinosaur Phylogenetic Tree

Contributed by Alli Weis

This week’s blog post is inspired by a new hypothesis that has emerged this month, published in the journal Nature. Essentially, for years the widely accepted theory of Dinosaur relationships has been based on dividing Dinosaurs into two main categories. The division was based upon the hips, or the pelvic anatomy. One category was classified as “bird-like”, known as Ornithischia and the other being “lizard-like” and known as Saurischia. For nearly a century now, the two groups have been classified as separate and thought to have two distinctly different ancestors lineages. This new study has found evidence for another option. They say that they have found a sister-group relationship between Ornithischia (bird-like pelvis) and Theropoda, and named that group “Ornithoscelida”. Further, Sauropodomorpha and Herrerasauridae are now in a refined grouping of Saurischia.

What this means is that now tens of dinosaur scientists (perhaps hundreds? How many are there?) are currently pouring over the data, reanalyzing it and coming up with rebukes to this new controversial theory. Science! Importantly it is a great example for the need to always challenge the central dogma in any field, and, as new molecular data emerges and new computer programs are developed to assist in the analysis and interpretation of data, it’s important to challenge old theories and hypotheses of the past. Somewhere along the road we stumble upon the truth.

Here is the paper:

http://www.nature.com/nature/journal/v543/n7646/full/nature21700.html

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Communicating Goals and Expectations

Contributed by B. Carol Huang

Goal setting is very important for anyone who wishes to have an achievement. The goal is like a blueprint for a building project, a road map for a journey, in which it will answer the questions like what, why, how and when.

What: answers destination, mission, and vision.

Why: answers the importance and value of the project and vision.

How: will lay out the routes, approaches, protocols, strategy to take, plus people will be involved.

When: makes progress steps measurable and traceable. It can be dissected into long term and short term (weekly monthly or daily)

Goals should be SMARTS: be specific on what you what to accomplish; set a timeline for when goals will start, where to start and how to proceed. M: goals need to be measurable, quantify or a timeline would help. A: achievable, goal setting is the first step toward the accomplishment, if it is not achievable it is not a goal. R: realistic, do not set goals so low so there is no challenge to promote the growth. T: a goal should be tangible.

Without a goal it is like a journey without a trip plan, driving without a destination. Having a clear set of goals will help to motivate people to achieve more and efficiently. If I tell people I will get a degree, obviously, people would ask me what is my current level of education, what is the reason I am seeking this degree l, what is the next level I want, and my interests. I will need to find professors in the desired field, prepare my application and know when to start as well as the expected time to finish.  Once I am admitted, a more detailed plan will be made with a professor.

Back to the title, Communicating Goals and Expectations. In a workplace, goal setting will involve two parts: group goals, and individual goals. For better goal delivery,  you need to recognize people who will be involved and clearly communicate your goals with them. You will also need to provide people with context and expectations as well as each one’s role and responsibility in the process.  Based on the group’s big platform individuals will align their goals with the group’s goal to reach the desired achievement.

No goal, no go.

 

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3-D tissue culture models to mimic human gut infections

Contributed by Nguyet Kong

3-D tissue culture models to mimic human gut infections

In an article from npj Microgravity, scientists have reported their latest advancement in 3-D intestinal model development where they want to develop more realistic model to prevent Salmonella from causing food poisoning and disease around the world. Salmonella infections have increase over the years and scientists are worried about finding new ways to improve their research faster than the infectious diseases. The 3-D tissue models are used to more accurately reflect how our bodies will respond to the pathogen. The scientist didn’t have the ability to understand the infectious disease fully due to the lack of models. With the three-dimensional models, they can better predict how people can respond to infection and understand how the cells and tissues in our bodies will function. A new study between Arizona State University and NASA Johnson Space Center, their goal is to make more realistic models that can more accurately reflect how the body will respond to the pathogen. One goal is to prevent Salmonella infection that can sometimes lead to death. In their model, they have incorporate an immune defense cell type, macrophages, they believe it is a key cell type during Salmonella infection. This allow the scientist to see how the macrophages and the epithelial cells interact during this host-microbe interaction study. The scientist have used a multi-drug resistant Salmonella strain that caused an epidemic in Africa for this study, they wanted to better understand the host-microbe interactions and infectious disease mechanisms to allow them to develop new needed vaccines and drug development for their infectious diseases.

Jennifer Barrila, Jiseon Yang, Aurélie Crabbé, Shameema F. Sarker, Yulong Liu, C. Mark Ott, Mayra A. Nelman-Gonzalez, Simon J. Clemett, Seth D. Nydam, Rebecca J. Forsyth, Richard R. Davis, Brian E. Crucian, Heather Quiriarte, Kenneth L. Roland, Karen Brenneman, Clarence Sams, Christine Loscher, Cheryl A. Nickerson. Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns. npj Microgravity, 2017; 3 (1) DOI: 10.1038/s41526-017-0011-2

http://www.rdmag.com/article/2017/03/3d-tissue-culture-model-mimics-gut-infections

 

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Science vs politics?

Contributed by Ning Chin

The advancement in science is often pursued because technological improvement is supposed to improve our life. Researches in biological sciences are especially important to improve our health and general wellbeing. But science does not get implemented in our daily life quick enough. This is partly due to the rigorous self-policing nature of the scientific community in making sure that all the facts line up correctly, which is good. Another part has nothing to do with science and facts itself, but on policy-maker. With the recent change in White House, people are concerned about the president’s acknowledgement of the scientific facts. We always like to think that a person’s life is invaluable – everybody has the right to live. However, this is not the case. The cost and procedure of getting health care in the U.S. is way too complicated.

The lag between scientific discovery and its implementation cost lives. I recently attended Dr. Joe DeRisi’s talk in UC Davis, hosted by the Integrative Pathobiology grad group on campus. He talked about several clinical cases where medical doctors misdiagnosed patients based on symptom-based-diagnosis, causing the patients to suffer; while a quick RNA sequencing was able to diagnose the culprit for the disease – some patients could have been cured earlier and spend less money. Real improvement of sciences is when it is accessible to the general public. However, scientific advancement is always slow because of other social issues – politics, poverty, debate on human rights, etc. Genome sequencing is extremely useful in forensic science – but we can’t have a whole genome sequencing database because people are worried about privacy issues – worried about how is that going to cost them if their health insurance finds out.

There are diseases where our scientific knowledge is still not enough to cure it. I’m confident that someday we’ll find a cure, because scientific knowledge is being built-onto by researchers all over the world. But there are also curable diseases that happens only because people who have the power to decide, decide not to help. Do these people die of illness? Or poverty?

Other resources:

http://www.commonwealthfund.org/publications/press-releases/2015/oct/us-spends-more-on-health-care-than-other-nation

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Sequencing and publication of 306 Listeria monocytogenes genomes

Contributed by Poyin Chen

Listeria monocytogenes is a foodborne pathogen prevalent in environmental and food matrices including soil, fruit, and deli meats. This organism encompasses 13 serotypes, among which serotypes 1/2a, 1/2b, and 4b are most commonly associated with disease including gastroenteritis and abortions. Listeriosis accounts for less than 1% of foodborne illnesses worldwide yet carries the highest highest foodborne mortality rate (16%) with immunocompromised, pregnant, young, or old individuals at risk. When contracted during gestation, listeriosis results in miscarriage, stillbirths, or premature labor leading to infant mortality. Transmission is facilitated by its capability to proliferate at low temperatures and tolerate heat, acid stress, and salt stress, necessitating L. monocytogenes-specific sanitization protocols in processing plants.

Recent years have seen a spike in multistate outbreaks of listeriosis due to food contamination including deli meats, dairy, hummus, cantaloupe, and stone fruit, leading to recalls of contaminated products, resulting in millions of dollars in lost revenue. Genomic comparison of these outbreak strains with environmental isolates via whole genome sequencing will shed light on the genetic factors that potentiate L. monocytogenes virulence. Already we are expanding our knowledge of the genome organization and gene content of this pathogen.

Our recent sequencing and announcement of 306 L. monocytogenes genomes will allow for a greater understanding of L. monocytogenes biology and help to update current classification schemes.

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Importance of sialidases during infection

 

Contributed by Narine Arabyan

Sialidases, also known as neuraminidases, are widely distributed in nature and are found in organisms from Eukarya, Eubacteria, and viruses. Sialidases are glycosyl-hydrolases that cleave the α-ketosidic bond of a terminal sialic acid residue from complex glycans. Sialidases have been implicated and correlated with several diseases. Sialidases play a critical role in microbiology by mediating metabolism, adherence, and infection, and are important regulators of alternate complement pathway activation, red blood cell destruction, cell growth, cell adhesion, and tumor metastasis in mammalian systems1-5. Recently, the importance of sialidases in infection and commensalism, has come to light opening the potential to use newly measured genomic diversity as a means to investigate infection mechanisms.

Sialidase presence is highly correlated with the progress and severity of the disease and the most probable role of sialidase is for successful attachment and colonization. Microbes use sialidases to reveal the cell surface that holds sialic acid-containing cell membrane receptors during infection. Arabyan et al. elucidated how sialidases play an important role by altering the host glycan profiles during infection to gain access of the host epithelial cells by binding to terminal sialic acid receptors to initiate glycan degradation6. Weimer’s group demonstrated that the two sialidases from Salmonella enterica Typhimurium LT2 have the same domains and function as sialidases, however they are structurally very different, indicating domain shuffling and lack of structural conservation6.

Bacterial, viral, and trypanosomal infections of humans and livestock can result in serious medical complications and economic loss. Though antibiotics are available for the treatment of bacterial infections, inhibitors of all sialidases and new drug targets may be medically useful where sialidase activity has been correlated with severe infection pathology. Microbes use sialidases to reveal the cell surface that holds sialic acid-containing cell membrane receptors during infection. In addition to targeting host glycoconjugates, sialidases from Streptococcus pneumonia and Pseudomonas aeruginosa also act as a molecular signal for biofilm formation needed during lung infection. Alternatively, some bacteria (Pseudomonas spp., Haemophilus spp.) use the cleaved sialic acids to sialylate structures on their cell surface, such as flagella, capsule polysaccharide (CPS), or the lipopolysaccharide (LPS), to mask the pathogen from the host immune system. The recent emergence of novel avian A H7N9 influenza virus in poultry and humans in China has shed new light on influenza virus adaptation to mammals using their sialidases. Shi et al. showed that H7N9 appeared to jump the species barrier7. The biological trait required for animal influenza viruses to cross the species barrier is the increased receptor binding specificity for α-2,3sialic acid for avian viruses or α-2,6 sialic acid for human influenza virus8.

 

References

1          Walther, T. et al. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog 9, e1003223, doi:10.1371/journal.ppat.1003223 (2013).

2          Imai, M. & Kawaoka, Y. The role of receptor binding specificity in interspecies transmission of influenza viruses. Curr Opin Virol 2, 160-167, doi:10.1016/j.coviro.2012.03.003 (2012).

3          Varki, A. & Gagneux, P. Multifarious roles of sialic acids in immunity. Ann N Y Acad Sci 1253, 16-36, doi:10.1111/j.1749-6632.2012.06517.x (2012).

4          Chan, R. W. et al. Infection of swine ex vivo tissues with avian viruses including H7N9 and correlation with glycomic analysis. Influenza Other Respir Viruses 7, 1269-1282, doi:10.1111/irv.12144 (2013).

5          de Graaf, M. & Fouchier, R. A. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J 33, 823-841, doi:10.1002/embj.201387442 (2014).

6          Arabyan, N. et al. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep 6, 29525, doi:10.1038/srep29525 (2016).

7          Shi, Y. et al. Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses. Science 342, 243-247, doi:10.1126/science.1242917 (2013).

8          Ichimiya, T., Nishihara, S., Takase-Yoden, S., Kida, H. & Aoki-Kinoshita, K. Frequent glycan structure mining of influenza virus data revealed a sulfated glycan motif that increased viral infection. Bioinformatics 30, 706-711, doi:10.1093/bioinformatics/btt573 (2014).

 

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Ebola Update

Contributed by Allison Weis

Two years ago, beginning in March 2014, the world saw the largest outbreak of Ebola in history. The outbreak was massive, all countries affected combined 28,646 people were infected and of those 11,323 people were killed by the virus (WHO). During the time of the initial outbreak the world was terrified. Not only did we not have a vaccine, we also didn’t have a good treatment. Ebola is one of those rare viruses that is incredibly deathly – about half of the infected die and the deaths seem virtually unstoppable. The countries most affected were all in West Africa: Sierra Leone (3,956 deaths), Liberia (4,809 deaths) and Guinea (2,543 deaths). Mali and Nigeria were also somewhat affected with 6 deaths in Mali and 8 in Nigeria (WHO).

In March, 2016, a full two years after the global crisis, the WHO director general announced an end to the public health crisis. Since the control of the initial outbreak, there were still a number of flare-ups during 2015. For example, in Liberia there was 1 case and 192 contacts in March 2015, which was likely due to sexual transmission of the virus (CDC) and 3 cases in November 2015. Sierra Leone had 6 cases and 840 contacts in August 2015, which shrunk to 1 case by that September. By March 2016, by which the outbreak was established as no longer a health crisis, there were combined 13 cases in Guinea and Liberia and 1200 contacts- sexual transmission being the suspected means of infection.

On the vaccine development front, a lot of progress has been made. Prior to the outbreak, there was no vaccine and only a few labs in the world were even working on Ebola. Now, we have developed a protective vaccine that is in its first stages of distribution and we have stockpiled an emergency supply. As of December 2016, the new Ebola vaccine gave 100% protection – and truly remarkable advancement in a very short time. Thanks to Congress and the Obama administration for the emergency funding, scientists and health professionals have been able to work with unlimited resources to develop, try (all through the trials) and are now beginning to implement the vaccine in the most affected areas (CDC; WHO; NYT). If a new outbreak were to flare, the world is now in a much better position to counter the virus.

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Congrats Alli Weis on her Large-Scale release of Camphlobacter Draft Genomes paper published in Genome Announcements

Large-Scale Release of Campylobacter Draft Genomes: Resources for Food Safety and Public Health from the 100K Pathogen Genome Project

*Allison M. Weis,a,e Bihua C. Huang,a,e Dylan B. Storey,a,e* Nguyet Kong,a,e Poyin Chen,a,e Narine Arabyan,a,e Brent Gilpin,b Carl Mason,c
Andrea K. Townsend,d* Woutrina A. Smith,a Barbara A. Byrne,a Conor C. Taff,d*

*Bart C. Weimer a,e

School of Veterinary Medicine, UC Davis, Davis, California, USAa; Institute of Environmental Science & Research Ltd., Christchurch, New Zealandb; Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailandc; Department of Wildlife, Fisheries and Conservation Biology, UC Davis, Davis, California, USAd; 100K Pathogen Genome Project, UC Davis, Davis, California, USAe

A B S T R A C T Campylobacter is a food-associated bacterium and a leading cause of foodborne illness worldwide, being associated with poultry in the food supply. This is the initial public release of 202 Campylobacter genome sequences as part of the 100K Pathogen Genome Project. These isolates represent global genomic diversity in the Campylobacter genus.

To read the full article click here

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New Breath Analysis method to detect metabolites

Enhanced non-invasive respiratory sampling from bottlenose dolphins for breath metabolomics measurements

Konstantin O Zamuruyev1Alexander A Aksenov1Mark Baird2Alberto Pasamontes1Celeste Parry2Soraya Foutouhi3Stephanie Venn-Watson2Bart C Weimer3Jean-Pierre Delplanque1 and Cristina E Davis1,4,5

Published 30 September 2016 • © 2016 IOP Publishing Ltd 
Journal of Breath ResearchVolume 10Number 4

To read full abstract click here

 

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