Small Things Considered

Are You Me or Am I You?

by Elio

Growth of Proteus on an agar plate, starting from
an inoculum in the center. Source.

When one cell meets another, it must make decisions. This extends itself to practically every attribute of living things, from avoiding mating with self to the establishment of territorial boundaries. Do we fuse? Will you attack me? Are you a potential mate or are you lunch? And, in the bodies of vertebrates, are you something that my immune system should recognize as foreign? Microbes are not exempted from these quandaries, being that they carry out lively conversations for purposes as diverse as feeding, differentiating into biofilms or fruiting bodies, moving, surviving in a host, or sensing their own numbers. As with the social insects, microbes converse in a chemical language. As Strassman et al. say in an insightful review: Recognition seems likely to be particularly important to microbes because they undertake many processes extracellularly in the public sphere that larger organisms privatize inside.

In studying such microbial interactions, one can choose among a number of interesting models. The Gram-negative bacillus, Proteus mirabilis, practically begs us to select it.

Two New Books (with my name on the spine)

by Elio

When I’m not blogging, I tend to get involved in book publishing. Twelve, so far. Mostly what I do is editing, although I have been an honest co-author for a few. My most recent venture was a project somewhat simpler than most. I had served as the editor-in-chief of the 3^rd edition of the Encyclopedia of Microbiology (Elsevier) and was approached by the publishers to put together two ‘derivatives,’ that is, books drawn from the encyclopedia but centered on one or area or another. The appeal to me was that it was comparatively little work, plus the books could be offered at a relatively low price, given that most of the cost had been incurred already.

One of the two, Topics in Ecological and Environmental Microbiology, was edited by Tom Schmidt, an experienced microbial ecologist, and myself. It is comprehensive, with 48 chapters divided into five major sections: Microbial Ecology, Metabolism and Behavior of Diverse Microbes, Microbial Habitats, Biogeochemical Cycles and their Consequences, and Biotechnological Topics. For the table of contents, click here. We believe that it will serve well as a reference work, with a lot of material between the covers.

Ringing a Microbial Dinner Bell

by Mark Martin

An adult hoverfly, also known as a flower fly. Source.

A few weeks ago, I wrote a short Small Things Considered essay describing the diverse roles that odors can play in microbiology. Articles here and there written by others attest to a growing interest in sociomicrobiology. As for myself, I have long suspected that microbes are constantly sending and responding to a wide communication ‘bandwidth’ of rich chemical chatter, and that other organisms can use or eavesdrop on those signals. Such communication is common in the eukaryotic world, conveyed by a variety of chemical messages or semiochemicals with myriad effects.

Thus, I was charmed by a recent article by Pascal Leroy and coworkers, as well as the accompanying Research Highlights essay. The researchers report how it is that the hoverfly Episyrphus balteatus is able to locate its prey, the pea aphid Ayrthrosiphon pisum. As you might guess, reading this blog, there is indeed a microbial component to this story.

Is a Good Offense the Best Defense?

by Merry

The budding yeast, S. cerevisiae. © Eye of Science/
Photo Researchers, Inc. Used with permission. Source.

Most eukaryotes possess an RNA interference system (RNAi) that they use to regulate gene expression and to defend against viruses and other mobile elements. However, some budding yeasts, such as Saccharomyces cerevisiae, appear to get along just fine without it even though RNAi has benefited other yeasts by silencing transposons in particular. How do these yeasts that lack functional RNAi systems compete with closely related species that do? And how come they don’t have RNAi when RNAi arose in an early eukaryote ancestor and is conserved throughout most of the fungi?

Virus Hacks Intercellular Communications Network

by Merry

A T cell (blue), a type of lymphocyte, in contact with
the dendritic cell beneath it. Credit: Lawrence Berkeley
Lab. Source.

What do monocytes, lymphocytes, and neutrophils all have in common? Well, yes, they are all leucocytes and part of our immune system, but what else? They all can be prompted to migrate to the site of infection by a specific class of cytokines known as chemotactic cytokines, or chemokines for short. These chemokines are made by a wide variety of cell types, including macrophages, various blood cells, epithelial cells, endothelial cells, and, of particular interest here, by numerous human tumor cell lines, melanoma cells, and liver cells infected by hepatitis C virus. Some chemokines function to direct cell migration during normal processes, such as embryogenesis, lymphoid organ development, and haematopoiesis. The chemotactic responses they incite can be quite specific, with different cell populations responding to different chemokines, of which there are more than 40, classified into four families. They’re all small proteins (~8–10 kDa), all have the same characteristic structure, and all are homologous, with 20–50% amino acid identity. That much divergence in sequence provides plenty of opportunity for specificity of action.

Diagram showing a chemokine with its typical,
conserved fold within the lumen of a blood
vessel. The chemokine is interacting with a
glycosaminoglycan (GAGs present on the sur-
face of an endothelial cell lining the vessel.
From there, the chemokine is presented to the
seven-transmembrane domain signalling recep-
tor in the membrane of a passing leucocyte.
Receptor binding involves multiple regions of
both the chemokine and the receptor. The key
motifs involved are labeled here. Source.

The receptors for these intercellular communication molecules  lie on the surface of the leucocytes, and they, too, are a diverse lot—at least 19 different ones are known. They also have their own commonality: a structure with seven-transmembrane domains to securely anchor them in the cell membrane and a coupled G protein. Along comes their cognate chemokine secreted by some cell at the site of infection. The chemokine binds to the receptor, and the coupled G protein initiates an intracellular signaling cascade that can affect multiple pathways. Actually, it’s a little more complicated. Chemokines bind first to the surface of the endothelial cells lining the blood vessel via GlycosAminoGlycans (GAGs). This keeps them from being washed away by the bloodstream and positions them for binding to receptors on passing leucocytes. (See the figure to the left.) For an effective inflammatory response, the leucocytes also need  to be shown which way to go. The GAGs are essential here, too. The chemokines bound to the GAGs along the blood vessel establish a stationary chemokine concentration gradient around the site of infection. When a leucocyte binds a chemokine, it ‘crawls’ along the chemotactic gradient and then undergoes diapedesis to migrate into the tissue space.

Talmudic Question #81

Given that most mutations are deleterious, why does the mutation rate not evolve to zero?

A Pestis from the Past

by S. Marvin Friedman

The plague victims at East Smithfield burial ground. Photo repro-
duced courtesy of the Museum of London Archaeology. Source.

In recent decades we’ve come to realize that victory goes not to the swift or to the strong, but to the immune. The introduction of agents of deadly diseases into immunologically naïve populations determined momentous events in human history. The conquest of the Americas resulted in good part from the decimation of native people by diseases brought by the Spaniards, such as smallpox and measles. Two seminal books, one by William McNeill and the other by Jared Diamond, come to mind, followed recently by one by Irwin Sherman. It follows that students of historical human affairs need also a solid background in the affairs of microbes. The methods now available to paleomicrobiologists allow us to travel back in time and probe microbial events that took place in the distant past. One approach, determining the genetic sequence of ancient microbes, while still a daunting task, is providing exciting glimpses into the history of humans and their pathogens, as shown in a paper I will discuss here.

(c) Geographical origin of genome sequences used
in a and b (see later figures). (d) Geographical spread
of the Black Death from infection routes. Source.

As the Black Death or Plague spread throughout Europe from 1347-1351, it claimed about 30 million victims or roughly 40% of the population. It is widely thought to have been caused by the Gram-negative bacterium Yersinia pestis. Y. pestis recently evolved from the soil-dwelling bacillus Yersinia pseudotuberculosis and in the process acquired two more plasmids (pMT1 and pPCP1) that enabled this highly contagious pathogen to invade mammalian hosts and cause disease. Like its ancestral Y. pseudotuberculosis, it also hosts a pCD1 plasmid. A multinational research team from Canada, Germany, and the United States has now presented a draft genome of Y. pestis from the time of the Black Death. Included in their report is this ancient microorganism’s chromosome (4.6 megabases) and the two remaining plasmids, pCD1 (70 kb) and pMT1 (100 kb), some of the same investigators having previously sequenced pPCP1 (9.6 kb).

Fine Reading: Adaptations to energy stress dictate the ecology and evolution of the Archaea, by D. L. Valentine

by Elio

It's been over thirty years since Carl Woese discovered the Archaea, yet they still qualify as the most puzzling of the domains of life. Many of them are extremophiles, but not all, and they differ from the Bacteria in significant ways, such as their rRNAs and tRNAs, the lipids in their membrane, and how they synthesize macromolecules. Yet typical members of the two domains tend to be similar in size and body plan, and, when compared with the eukaryotes, they have a more confining developmental repertoire. In distinguishing between Archaea and Bacteria, we are helped by an insightful paper by David Valentine, who proposes that the difference between them resides in the Archaea being better adapted to energy stress, something that sooner of later all free-living organisms experience. Included in the argument are not only the extremophilic Archaea, but also those living in a more ‘regular’ environment, such as nitrifiers and methanogens.