mBiosphere

From one tiny room to a $26 billion budget: Joseph Kinyoun's NIH

The National Institutes of Health (NIH) today is the world's largest biomedical research institution, but back in 1887 it began its existence as a one-man immigrant quarantine station on Staten Island. The authors of a Minireview in mBio today tell the story of NIH's early growth with a biography of the Institute's founder, Joseph James Kinyoun (1860-1919).

At 125 years old, the NIH is now comprised of 27 Institutes and centers and is responsible for $26.4 billion in annual spending on both grant-based extramural funding and on its own intramural biomedical research program, but every mighty oak begins with a small acorn. The NIH began as the Hygienic Laboratory, an arm of the Marine Health Services, employing 25 year old Dr. Kinyoun (rhymes with “pinion”) as chief of a lab that occupied what once was a tiny museum room. The station served as a diagnostic laboratory to support quarantine activities to prevent new cases of cholera, plague, smallpox, and yellow fever from entering the country. Decades later, after several relocations, the Hygienic Laboratory would be known as the NIH.

Morens and Fauci's Minireview traces Dr. Kinyoun's career prior to his position at the Hygienic Laboratory, the aspects of his research program that helped propel the newly minted field of bacteriology forward, and the personal tragedies that compelled him to continue his work on preventing and curing infectious disease.

Amphibian-killing fungus: is one gene family responsible for the downfall of frogs?

Recent headlines highlight the alarming rate at which species are being forced into extinction, and amphibians are particularly vulnerable. Up to 41% of frog, toad, newt, salamander, caecilian, and other amphibian species are listed as Vulnerable, Endangered, or Critically Endangered, and although habitat loss and other factors play a role in these extinctions and near-extinctions, it is now clear that a pathogenic fungus is responsible for the threatened state of many amphibian species. Batrachochytrium dendrobatidis, often called chytrid fungus or Bd, causes chytridiomycosis, a disease that strikes entire populations, causing widespread declines that can eventually lead to extinction.

But the Bd picture is far from complete. We know that Bd causes an electrolyte imbalance in amphibian bodies, and that it may suppress the immune system to some extent, but we have little understanding of its pathogenicity on a molecular level.

John Abramyan and Jason Stajich of UC Riverside examined the genomes of two Bd isolates to find clues about its pathogenicity, reasoning that since Bd is the only known amphibian pathogen in its phylum, its genome must bear the marks of restructuring to adapt to its new environmental niche and exploit its amphibian hosts. Other fungal lineages that evolved into pathogens or adapted to new host types have gained or lost genes and often showed signs of lineage-specific expansions of certain gene families and domains within a gene. Does Bd have telltale genome differences like these that could give away how the fungus causes disease?

Abramyan and Stajich say "yes". Compared with its fellow phylum members, Bd genomes have an expanded number of genes in the Carbohydrate-Binding Module Family 18 (CBM18), a family of proteins linked to pathogenicity in other fungal species. The expansions have been limited to three categories of genes, each of which has been implicated in host-pathogen interactions in the past.

This expansion in CBM18 could well mean it plays a role in the mode of pathogenicity of Bd an offers clues for future work to elucidate the why and how of chytrid disease in amphibians.

The results may also lead to a better understanding of the ecology of Bd and how it might be controlled. The authors predict that one of the categories of genes affected, lectin-like genes, function as lectins, possibly binding chitin in the way other lectin-like genes do in other fungal species. In other fungi, chitin-binding molecules protect the fungus from attack by plant chitin-targeting enzymes, and could protect Bd from amphibian chitinases. Or Bd may use its ability to bind chitin to attach itself to chitin-containing structures outside the host. This may mean Bd can attach and survive in ponds and wet places amphibians live, a crucial piece of knowledge that, if true, could have serious implications for amphibian conservation and eradication of the fungus.

Salmonella gooses the human host to boost its own fitness

A gene Salmonella picked up from a virus apparently enables it to tweak the human gut to get what it needs to outcompete its neighbors, according to the latest study published in mBio this week.

A multi-drug resistant strain of Salmonella that caused an outbreak among both humans and cattle in the 1980's carried a gene called sopE. sopE is not your average Salmonella gene: it's a virulence factor the bacterium acquired from a phage. Overall, sopE is present in only a small fraction of Salmonella isolates, but it was all over the human-and-cattle-epidemic strain like white on rice. It's an effector protein of the invasion-associated type III secretion system and it's a potent inducer of inflammation in the intestine, but what sort of advantage does it offer to Salmonella that made it so successful in this outbreak? What does sopE do, exactly? Figuring this out could help control outbreaks in the future (and rest assured there are plenty of Salmonella outbreaks in our future).

Researchers at UC Davis (Go Aggies!) studied the action of sopE in mice. They found that by inducing the host to make inducible nitric oxide synthase, sopE enhances the production of host-derived nitrate, enabling the bacterium to live off nitrate, a valuable electron acceptor in this dog-eat-dog anaerobic habitat. This provides a growth advantage for Salmonella, boosting its numbers in the lumen.

In a tidy little turn of events, when Salmnonella has access to nitrate in the gut it turns down the respiration of another, less valuable electron acceptor: tetrathionate. Without sopE, Salmonella uses tetrathionate for its "breathing" needs, expressing genes for tetrathionate respiration so that it can survive in the anaerobic gut. But when sopE is on hand to help Salmonella extract nitrate from the host, the bacterium reduces the expression of tetrathionate respiration genes. This ensures the bacterium uses the optimal electron acceptor, nitrate, and maximizes its growth rate, allowing it to outcompete other bacteria in the gut. 

Salmonella gooses the human host to boost its own fitness

What you're reading

We've been watching you, and we like your taste in microbiology. Here come mBio's most read papers of the past month. Drumroll, please?

Coming in at #3: A commentary on the potential application of phage therapy in cystic fibrosis. Pseudomonas Biofilms, Cystic Fibrosis, and Phage: a Silver Lining? mBiosphere featured this Commentary back in April. 

mBio's 2nd most read paper this month? Evidence that antibiotics on the farm can lead to resistance. Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock This was a significant paper. Some of the first hard evidence that using sub-therapeutic doses of antibiotics in farm animals can encourage resistance in human pathogens. Again, this was discussed on the blog. 

And finally, our most read paper of the month: The Black Queen Hypothesis: Evolution of Dependencies through Adaptive Gene Loss. A new take on how bacteria do more with less. And you guessed it! The BQH was also discussed on the blog.