Pacifying our microbes – a way to prevent resistance evolution

On November 25th, Jon Femling MD PhD will give a lecture for the Evolutionary Medicine class. His talk will focus on the topic of microbial virulence evolution, pointing out several novel ways to prevent the evolution of antibiotic resistance using molecules that target virulence without killing microbes.

Jon Femling MD PhD

Dr. Femling will discuss ways to inhibit quorum sensing and virulence  gene expression in Staphylococcus aureus, transforming this often deadly bacterium from an enemy to a friend. Since this strategy does not kill the bacteria, it is expected to limit selection for antibiotic resistance.

Targeting Agr Quorum Sensing Inhibition in Staph

 

His recent paper can be read in its entirety here:

Selective Chemical Inhibition of Agr Quorum Sensing

Extra reading: Evolution of virulence. Ewald PW. 2004. Infect Dis Clin N Am (18)

There is no writing assignment this week. Work on your final presentations.

 

Extra – the gut microbiome has rhythm

A remarkable study pointing to gut microbiota involvement in jet lag was recently published in Cell by Elinav and colleagues : Transkingdom control of microbiota diurnal oscillations control metabolic homeostasis.

Until now, little recent evidence has linked sleep with gut microbiota. This study changes that. A major finding of Elinav’s group is that gut microbiota have a circadian rhythm, with gene expression and population numbers that cycle in circadian fashion:. For example Lactobacillus populations expand and contract in the gut microbiome, depending on the time of day:

Thaiss et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 2014. 159 (3) 514-529

Thaiss et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 2014. 159

This group showed that the gut microbiota follows a circadian rhythm, just like host cells. Moreover, they showed that healthy cycling microbiotas require a host that follows a normal circadian pattern of eating and sleep. When the mouse sleep and eating pattern is disrupted, their microbes lose their rhythm. When this “jet-lagged” microbiota is transplanted into germ free mice, the inoculated mice become fat and lose glucose control, that is, they exhibit a pre-diabetic state.

Circadian microbiota graphical abstract

The investigators also studied humans who suffered jet lag. Two subjects with 10-12 hour time change gave fecal samples before, during, and after resolution of jet lag. The samples were inoculated into germ free mice. Lo and behold, the mice receiving jet-lagged poop became obese and pre-diabetic, exhibiting glucose intolerance:

Jet lagged human microbiota causes metabolic changes

Jet lagged human microbiota causes metabolic changes in mice

I interpret these findings to mean that all our body’s activities, and those of our microbiota, have evolved to be on a timer. Mistimed sleep and eating has real consequences, increasing the risk of obesity, diabetes and many other diseases. In an editorial accompanying the Thaiss et al. paper, the question is raised whether similar changes in microbiota and metabolic control occur in humans who work night shifts. Coincidentally, our group at UNM is studying this very question. The UNM Department of Emergency Medicine is currently studying the effect of shift work on the microbiome and immune system. Since we emergency physicians work day shifts and night shifts: we are the shift-workers that we will be studying.

Stay tuned.

Guest lecturer Melanie Martin November 18

Melanie Martin will be giving a guest lecture Nov 18, 2014 at 5:30pm for the evolutionary medicine class and UNM community:

Becoming your microbiome: how early life shapes human microbial composition and function

Melanie Martin is a biological anthropologist who studies how variation in nutritional and microbial ecologies shape infant feeding practices and health outcomes. Since 2009 she has worked with the Tsimane, an indigenous forager-farmer population in the Bolivian Amazon. She has published research on Tsimane maternal milk fatty acid composition and parasitic coinfection risk, and is currently studying how maternal and infant fitness trade-offs influence Tsimane breastfeeding practices. She is also collaborating with researchers at UNM, Los Alamos National Laboratory, and Stanford to examine the influence of specific feeding practices on Tsimane infant gut and salivary microbiomes.

Melanie Martin with Tsimane kids

Reading for Tuesday’s talk: 1) Infant Gut Microbiota: Developmental Influences and Health Outcomes by Melanie Martin and David Sela

Visitors may find this map useful – Castetter is #21:

Castetter

Writing assignment for evolutionary medicine students due Nov. 18th

Up to 20% of the carbohydrate content in breast milk is indigestible by the infant! It might seem paradoxical and wasteful that the mother converts easily digested fuel (glucose) into indigestible milk oligosaccharides. Why doesn’t natural selection decrease or eliminate the production of oligosaccharides in human breast milk?

Additional Recommended Reading:

3) Human milk and infant intestinal mucosal glycans guide succession of the neonatal intestinal microbiota.

New England Journal on Antibiotic Resistance

Screen Shot 2014-11-10 at 12.05.18 AM

Nathan and Cars wrote a perspective piece on antibiotic resistance published 4 days ago in the New England Journal of Medicine. On about the same day, I gave a lecture to UNM emergency medicine residents on using evolution to mitigate antibiotic resistance and how to reduce the unintended consequences of selection on the microbiome.

I did a quick search of the recent NEJM article: amazingly, there is no mention of evolution. This omission perpetuates the misguided notion that evolution in unimportant in medicine. Most egregiously, the article made no mention of novel strategies for the prevention of resistance evolution. These include antibiotic cycling by Miriam Barlow, ways to reduce drug selection pressure by Andrew Read, and evolving bacteriophages to kill bacterial pathogens by Michael Hochberg.

Developmental origins of disease – lecture Nov. 11th – updated!

Developmental programming is thought to be a source of many adult diseases, including obesity, diabetes, and cardiovascular disease. The notion that early life experiences, including nutrient transfer from the mother in utero, can anticipate future environments and also shape the risk of later adult diseases has been termed the predictive adaptive response, or PAR.

This relationship first came to light when Barker documented a curious association between birth weight and adult cardiac events in British men. Babies born small had a higher risk of chronic inflammatory diseases as adults. These small babies have been described as adopting a “thrifty phenotype.” That is, nutrient deprivation as a fetus is thought to have shaped the developmental trajectory in these individuals. This shift results in reduced expenditure on muscle and increased energy storage as fat.

This Tuesday, we are lucky to have a special guest, Jack Baker PhD, who has published extensively on human development and evolution. He co-authored a chapter in the 2008 Trevathan textbook: Evolutionary Medicine and Health New Perspectives, entitled “Evolutionary Medicine and Obesity: Developmental Adaptive Responses in Human Body Composition. More recently, Dr. Baker has published work that fits with expectations of the predictive adaptive response among the Ache in Paraguay, and some results that seem to conflict with the PAR. He teaches a course in Evolution and health in the UNM Anthropology Dept.

Jack Baker PhD

Jack Baker PhD

In preparation for Tuesday, first read this Carl Zimmer piece in Friday’s Times about cortisol in mother’s milk having lasting effect on their offspring’s behavior:

Screen Shot 2014-11-07 at 9.52.16 PM

Click on the image for the Zimmer article. Photo by Kathy West from NYT

Readings:

1) Kuzawa Evolution developmental plasticity, and metabolic disease

2) Birth Weight and Coronary Heart Disease

3) Birth Weight and Insulin Resistance

Late addition:

3.1) PNAS-2013-Hayward PAR

Optional:

4) Developmental Origins of Obesity

5) Gluckman Effect of in Utero and Early Life Conditions on Adult Health and Disease

6) Predictive Adaptive Response

In keeping with the last two weeks, there will be no writing project. Instead, find examples from  the internet how early life experiences change the body’s development in ways that cause disease? Could these changes also be adaptive, or not? (Try using the search terms “Predictive Adaptive Response” and or “Developmental Origin of Health and Disease” or DOHAD)

Maley and Aktipis Lecture Schedule for Monday and Tuesday

http://scopeblog.stanford.edu/2010/02/03/the_not-so-immo/

HeLa Cells. Asae Igarashi image, Kyowa Hakko Kirin Co., Ltd., Japan. Image by GE Healthcare from Flickr.

Dr. Carlo Maley, from the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, will present, An Overview of the Evolutionary Biology of Cancer.On MONDAY, November 3 at 12:00PM (lunch will begin at 11:30AM) in 107 Castetter Hall.

Dr. Athena Aktipis, from the Center for Evolution and Cancer at the University of California, will present:
“Beyond tit-for-tat: Computational models of human sharing and the evolution of sociality”Tuesday, November 4, 2:00PM; 57 Castetter Hall

and

Tuesday, November 4, 5:30PM; 258 Castetter Hall, guest lecture for the Evolutionary Medicine Class:
“Are cancer cells somatic cheaters? Cooperation and exploitation in multicellular bodies”

Evolutionary Medicine Students are encouraged to attend the extra two lectures on Monday and Tuesday (in addition to class).

There will be a reception/party for Dr. Aktipis and Maley on Monday night hosted by Steve Gangestad. Contact Steve or Joe Alcock for details.

Visitors may find this map useful – Castetter is #21:

Castetter

Click on the image to view the entire map