Weimer Micro Lab

Contributed by Carol Huang

The recent news about former president Jimmy Carter’s cancer has stopped spreading and is “responding well to treatment,” has drawn great attention to immunotherapy.

Carter, 91, announced in August that four spots of cancer, melanoma had spread to his brain. Then in early December he was told that recent tests have shown there is no evidence of new malignancy, and his original problem is responding well to treatment. Carter said he will continue taking his regular 3-week immunotherapy treatments of the cancer drug pembrolizuma, which has shown promise in the treatment of melanoma.

What is Immunotherapy? Immunotherapy is the treatment of disease by inducing, enhancing, or suppressing an immune response. Activation immunotherapies are to elicit or amplify an immune response; while suppression immunotherapies are to reduce or suppress immune response.

Activation cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors. Cell-based immunotherapies are proven to be effective for some cancers. Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells (NK Cell), cytotoxic T lymphocytes (CTL), etc., work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of the tumor due to mutation. Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent rejection of transplanted organs or cells.

The key for Carter’s promising result is his body’s immune system, cancer cells are responding well to the treatment.

https://en.wikipedia.org/wiki/Immunotherapy

Contributed by Bart C. Weimer, Ph.D.

Food microbiologists have wrestled with the concept of non-culturable bacteria (NCB). It is well accepted in environmental microbiology the NCB are common. The expanded importance of the gut microbiome has raised this issue to the forefront. The implications of NCB for food safety are extensive. If bacteria become NC in food there is room for extraction from the zombie state to cause disease. My group has long had interest in NCB. It first started with bacteria used in fermentation where we conclusively demonstrated that lactococci produce branched chain fatty acids only after entry in NC. A recent search produced only 6 papers for Salmonella NC and virulence. I was surprised. The data are not at all convincing that link NC in pathogens to virulence. The link between survival in the food supply and emergence of outbreaks is yet to be proven. This is an important link that needs attention!

Additional reading:

Shah, Jigna, Prerak T. Desai, & Bart C. Weimer. 2014. Genetic mechanisms underlying pathogenicity of cold-stressed Salmonella Typhimurium in cultured intestinal epithelial cells. Appl. Environ. Microbiol. 80:6943-53. (PMID: 25192993)

Shah, J., Prerak Desai, Dong Chen, John Stevens, and Bart C. Weimer. 2013. Proteomics of cold stress in Salmonella enterica sv Typhimurium LT2. Appl. Environ. Microbiol. 79:7281-7289. (PMID: 24056458)

Ganesan, B., M. Stuart, and Bart C. Weimer. 2007. Carbohydrate starvation causes a metabolically active but nonculturable state in Lactococcus lactis. Appl. Environ. Microbiol. 73:2498-2512.

Persistent Ganesan, B., P. Dobrowolski, and B. C. Weimer. 2006. Identification of the Leucine-to-2-Methylbutyric Acid Catabolic Pathway of Lactococcus lactis. Appl. Environ. Microbiol. 72:4264-73.

Contributed by Azarene Foutouhi

 Following a devastating earthquake in 2010 Haiti felt the beginnings of a Cholera outbreak. As in the case of many natural disasters, there was a resultant influx of aid in the form of supplies and volunteers from foreign countries, yet nearly five years later the outbreak seems to be getting worse. Only recently the infection rate which seemed to hold steady at a rate of one thousand new infections a month jumped to one thousand per week. After millions of dollars in aid, and months of humanitarian work, how has the outbreak not improved, and why is it getting worse?

 Cholera is an acute and potentially fatal disease which is caused by the ingestion of food or water by the bacterium Vibrio cholerae. The WHO estimates roughly 1.4-4.3 million cases annually, and a short incubation time of 2 hours to 5 days can result in an explosive outbreak. Sanitation and the maintenance of clean water sources are essential to maintaining a stable outbreak-free environment.

Where did the aid go? Soon after the earthquake, Haiti was flooded with foreign humanitarian aid: nurses, doctors, and supplies. However, recent reports have pointed out that while foreigners arrive assuming a nation–such as Haiti–has a shortage of specialized health workers, this is not usually the case, and that help without an informed context is little help at all. The initial aid did little to stop an outbreak in a country where many live in slums or the undeveloped countryside with no access to sanitation or clean water, and have to choose between the purchase of food and soap. As the aid workers left Haiti, little remained but the medical supplies they had brought with them and latrines in the cities.

 There is promise however, in the Cholera vaccine, which has been administered to approximately 300,000 people to date. However, with a nation of 10 million people there is much work yet to be done, and with an estimated price tag of 2.2 Billion to eradicate Cholera in the nation, people are left wondering when it will happen.

References:

http://www.who.int/mediacentre/factsheets/fs107/en/

http://annals.org/article.aspx?articleid=746955

http://www.npr.org/2015/06/02/411406390/haiti-sees-spike-in-cholera-cases-4-years-after-the-outbreak-began

Contributed by Ning Chin

The U.S. National Institutes of Health has devoted a considerable amount of research funds on the Human Microbiome Project. Since 2008, a lot of research was done to identify the species of bacteria existing on the human body. Human microbiome is defined as the community of bacteria that coexist with humans since birth. These bacteria function as another barrier to protect us from other harmful pathogens, as they physically occupy the available niches on our body where they flourish in communities. These studies have shed light on the bacterial community existing on both healthy and unhealthy individuals, especially in the gut. However, as we keep making discoveries, more questions arises with these findings.

Pharmacology, the study of drug action, is concerned with pharmacokinetics (how does the body reacts to a drug) and pharmacodynamics (what a drug does to the body). Bacteria in our gut are now known to affect both of these factors leading so labs to determine how we consume drugs personally for maximal effect – so called personalized or individualized medicine, now, more commonly called precision medicine. Phamacomicrobiomics, is a new area of science that investigates the effect of human microbiome on the action and disposition of drugs with the thought of enabling precision medicine based on the microbiome and the individuals own body chemistry. The term was first coined by Aziz et al. in 2011, but few studies have been conducted in this area. Over the weekend, I read an interesting article about how a diabetes drug, metformin, alter the gut microbiome to produce favorable compounds, further enhancing the result of the drug. Due to the close relationship between the human microbiome and our own chemistry, it is not so much a surprise to see that microbiome plays a role in how our body reacts to different chemical compounds, either enhancing the result or diminishing the result. This has been shown with antibiotics too. Our own lab has been involved in studies that demonstrate the effect of antibiotics to change the microbiome interactions and susceptibility to disease (Ferreyra et al., 2014). To fully understand the effects of drugs on human lifestyle, it is important to investigate the link between these drugs with our forgotten organ – our microbiome.

Additional reading and links:

Aziz RK, Saad R, Rizkallah MR. PharmacoMicrobiomics or how bugs modulate drugs: an educational initiative to explore the effects of human microbiome on drugs. BMC Bioinformatics. 2011;12(Suppl 7):A10. doi:10.1186/1471-2105-12-S7-A10.

Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Ferreyra JA, Wu KJ, Hryckowian AJ, Bouley DM, Weimer BC, Sonnenburg JL. Cell Host Microbe. 2014 Dec 10;16(6):770-7. doi: 10.1016/j.chom.2014.11.003. PMID: 25498344

http://pharmacomicrobiomics.com/

http://healthsciences.ku.dk/news/news2015/new-research-intestinal-bacteria-are-affected-by-antidiabetic-drugs/

Contributed by Roberto Torres

Helicobacter pylori is a gram negative bacterium which colonizes the human gastric mucosa. In the 1980’s, through biopsies and histological observations, Doctors Robin Warren and Barry Marshall proposed that peptic ulcers were caused by a gastric epithelial infection by a similar Campylobacter bacterium, and now we classify it as Helicobacter. This proposal caused high controversy because for a long time the scientific community believed that the acidic environment of the stomach made it a sterile organ. To demonstrate his theory, Dr. Marshall ingested an inoculum of Helicobacter, which caused him to develop gastritis a week later. The theory was accepted after the publication of his observations in the journal “The Lancet” in 1983. In 2005 Doctors Warren and Marshall were awarded the Nobel Prize in Medicine or Physiology for their research work related to Helicobacter and its role in the development of gastritis and peptic ulcers. After 30 years of this discovery and thanks to the hard work of microbiologists worldwide, it is well known that Helicobacter pylori is the main cause of gastritis and is the main risk factor for the development of peptic ulcers and intestinal type adenocarcinoma, being so far the only bacterium recognized as Type I carcinogen by the WHO. However, it is still not clear what bacterial factors determine the development of these different diseases. Today in the age of “Omics”, determination of these bacterial factors is a difficult task shared by microbiologists and bioinformaticians, even through the use of classical molecular techniques with the latest Whole Genome Sequencing procedures combined with Big Data processing.

Contributed by Nguyet Kong

The beneficial bacteria in the citrus tree is actually the Asian citrus psyllid (ACP), a pest that is the carrier spreading huanglongbing (HLB)

The Asian citrus psyllid (ACP), which spreads the pathogen believed to cause citrus greening disease, may be playing a role in Florida’s devastating outbreak. It is also found in Southern California too where the state of California is monitoring the spread. The ACP is a tiny mottled brown insect that is about the size of an aphid. ACP attack all different types of citrus and it actually aims for the new leaf growth where it injects the toxin that causes the new leaf tip to twist or burn back. The more serious damage is causing huanglongbing (HLB) disease, which is citrus greening that causes the citrus tree to die within 5 to 8 years with no cure. It causes the fruit to be asymmetrically with aborted seeds and bitter juice. A few other symptoms include unique yellow leaf mottling that is not the same on both sides of the leaf and the shoot and branch of the tree to turn yellow. Current citrus growers are treating this by applying  a wide range of pesticides to their tree several times a year to minimize the spread of HLB. It is hard to detect the symptoms because it may not show up for more than a year after the tree is infected. Monitoring practices can include yellow sticky cards to trap and detect adult psyllid, visual monitoring by examining new leaves where the adult psyllid lay eggs in new flush, and misting with a detergent solution to get the aphids off.

There is a new study where ACP, the citrus green bacterium effects the insect vector by changing inside the insect. During the infection, the pathogen affects the good part of the bacteria and alters the metabolism so it can spread the pathogen. The study reveals weak points in the transmission cycle that could yield high specific targets for control strategies that can be more effective and more environmentally friendly than using a lot of pesticides (PLOS ONE papers).

More information:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130328

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131917

http://www.ipm.ucdavis.edu/PMG/PESTNOTES/pn74155.html

https://www.cdfa.ca.gov/plant/pe/InteriorExclusion/acp_quarantine.html

Contributed by Poyin Chen

For my upcoming wedding, we will have a tree planting ceremony. As part of the ceremony, we will be planting our little love tree in soil from both of our families’ homes…a little from the Bay Area, and a little from Michigan.

Similar to how each person’s microbiome is unique, soil from different areas will have its unique mixture of microorganisms. What this mixture is is largely dependent on the surrounding environment. Perhaps my mom’s questionable homemade (fermented) fertilizer contributed some acid tolerant bacteria to our garden soil. Perhaps the drought conditions in California have favored the enrichment of bacteria resistant to dry conditions. These bacteria likely have thicker cell walls to withstand harsher conditions; maybe there are more bacterial spores in my Bay Area sample.

The soil we collected from Michigan was from under a mossy tree while the rain came down on us. Who knows which microbes were taking advantage of the wet conditions with some celebratory replication? One can only speculate on the small molecules being released by the tree’s root system and how they are influencing the structure and diversity of the surrounding soil microbiome.

I like to think that when we introduce our Bay Area and Michigan soil samples to each other under our little love tree, we will be initiating an intense, microscopic battle for resources. There will be rapid shifts in bacterial diversity in the days to come, and maybe even some bacteriocin production! When the dust settles, the outcome will be our own unique blend of soil microbiome underneath our love tree.

Contributed by Robin Jones

Happy Thanksgiving!  As I woke this morning my mind was filled with excitement for the upcoming events of the day.  The oven is already hot and in use, the house is beginning to smell of delicious treats, soon friends will be arriving, and the day will continue with a festive mood.  I am in the mountains of northern New Mexico this morning, Taos, to be exact.  The skies are becoming darker by the moment and the clouds are rolling in almost promising to give us a blanket of snow before the days end.  I honestly don’t think it could be more perfect!

My wish for everyone this morning (and always) is that whatever you do, be it today or every day of your life, is that you are happy. I hope that if you are celebrating at home that your home is full of laughter and joy.  If you are visiting others, may you be the joy that walks through their doors.  If you are working to serve others today, may each person recognize your service and be blessed by what you are doing, as I know you will be by serving those in need.  I hope you are surrounded by those you love and find peace and contentment in your hearts.

Happy Thanksgiving!

Researchers from McGill and Laval universities will receive close to $10 million over the next four years for work that is designed to both identify and find natural solutions for the reducing the growth of the salmonella strains that cause human disease.

This is one of two Quebec-based research projects that will receive funding from Genome Canada and Génome Québec under the program Genomics and Feeding the Future.”

To read full article click here.