Small Things Considered

A Most Personal Note

by Elio

Wonderful, wonderful Copenhagen
Friendly old girl of a town
                   Wonderful Copenhagen, lyrics by Frank Loesser

At the June General Meeting of the ASM in Boston, there was a session called From Bacterial Physiology to Cellular Genetics: Reflections on the 50th Anniversary of Schaechter, Maaløe, and Kjeldgaard. The participants were Fred Neidhardt, Stephen Cooper, Amy Vollmer, and myself.

Fifty years ago, it so happens, I was wrapping up my postdoc in the lab of Ole Maaløe (pronounced something like Moh-lö — "umlaut" on the o) in Copenhagen. It was also at that time that our two papers on growth physiology of Salmonella enterica var. Typhimurium appeared. (For PubMed citations to these papers, click here and here.) So, what is all this current fuss about? Our work and that of others led to the realization that when organisms grow in various media, their size and gross content of cell constituents (proteins, DNA, RNA, lipids, etc.) is directly proportional to their growth rate. The faster they grow, the more of these constituents they have. This holds true as long as the cultures are growing exponentially and thus are at a steady state. Two media differing in composition but supporting the same growth rate give the same measurements. We concluded that a bacterium can exist in any one of a number of physiological states depending on its rate of growth. As an illustration, cells of the same species observed under slow versus fast growing conditions can vary in volume by a factor of 10 or more!

This work helped clear up what had been a rather confusing state of affairs regarding bacterial growth. The classical, more-or-less S-shaped growth curve could now be interpreted as an exponential phase bracketed by two transitions, first from slow to fast growth and then from fast to slow growth (a shift up and a shift down). Details and further interpretations will soon be available in a review by Cooper recently accepted for publication in BioEssays.

What came of this?

Talmudic Question #34

We may be revealing our ignorance, but we are under the impression that although there are giant bacteria, there are no giant archaea. If this is the case, why might this be so?

Your Name and Occupation?

by Jennifer Gutierrez

The community under investigation.
Veg = vegetative cyanobacterial
cells; Het = heterocyst; Epi =
epibiont (Rhizobium sp. attached
to heterocyst); unatt. Epi =
unattached Rhizobium cells.

How would you like to be able to ask this question of an individual bacterium in its natural habitat—and get a truthful answer? It turns out that there is a way to do just that, thanks to a cool and innovative technique called Secondary Ion Mass Spectrometry (SIMS). A current version, known as NanoSIMS, is basically a high-resolution microscope and a mass spectrometer in one. Sweet! (For a review of this technology, click here.)

NanoSIMS has a resolution of 50 nm, which allows one to visualize single cells and to analyze their atomic makeup at the same time. Here’s how:

The Long Star State

by Kevin D. Young

There is nothing new under the sun.
         Ecclesiastes 1:9

King Solomon may be technically correct about the dearth of novelty, at least in its most general form. But that doesn’t mean we can’t be surprised, over and over, by things we’ve just discovered. For example, I would have thought that the basic shapes of bacteria would have been pretty well covered by now. After all, there are only a limited number of shapes available, right? Rods, spheres, and spirals seem to pretty well make up the bulk of the fundamental alternatives, with some variations on these themes and a few oddities thrown in for good measure. So it came as something of a shocker when Wanger et al. reported they had found a bacterium sporting a unique cell shape.

Ultrathin section transmission electron micrograph
of a six-pointed star. The cell envelope (12 nm in
thickness), which differs from that of both Gram-
negative and Gram-positive bacteria, possesses
the granular repeating structure characteristic
of a bacterial S-layer. Bar: 100 nm. Source

While looking at the organisms embedded in deep “mine slimes” (biofilms) in South Africa, they observed a filamentous bacterium that was star-shaped when examined in cross section. Star-shaped bacteria have been seen before (e.g., the genus Stella) and, of course, long rod shaped bacteria are common. What had never been observed was a combination of the two. The authors aptly describe the shape as looking like the children’s clay-like toy material, Play-Doh^©, after it has been extruded by pressing it through a star-shaped opening. Or, for that matter, like churros (“Spanish doughnuts”). Unexpected, unprecedented, and rather weird, actually.

Bloggers in Boston

by Elio

Elio Schaechter (this blog) holding
court at the Science Social Media
Breakfast in Boston.

On the occasion of the ASM General Meeting in Boston early in June, about a dozen of us interested in science blogs met for a discussion of blog-related issues. Several of the people in attendance were bloggers, notably Tara Smith of Aetiology, Jonathan Eisen of Tree of Life, Mackenzie Cowan of Diybio, and myself. Others were people interested in diverse blog-related isssues.

The Pathogen's Guide to Profiting From the Immune System

by Elio

Ah, that amazing innate immunity and those equally amazing ways microbes respond to it! There seems to be no end of the variations in the choreography of host and parasite. Here are two intriguing versions of that dance.

News from the Department of Mimivirology

Transmission electron micrograph of
cryo-fixed, sectioned, and stained
Mimivirus particle revealing a star-
shaped structure. Scale bar: 100 nm.
Source

Combine the new imaging techniques with the colossal and eyecatching Mimivirus, and you'd expect some stunning images. A recently published paper does not disappoint. The authors used several techniques to investigate how this virus packages its 1.2 million base pair DNA genome and then discharges it into an Acanthamoeba host during infection. Quoting the authors:

...we show that Mimivirus genome delivery entails a large-scale conformational change of the capsid, whereby five icosahedral faces open up. This opening, which occurs at a unique vertex of the capsid that we coined the stargate, allows for the formation of a massive membrane conduit through which the viral DNA is released. A transient aperture centered at an icosahedral face distal to the DNA delivery site acts as a non-vertex DNA packaging portal.

The Tip of the Iceberg

by David Hopwood

The position of erythromycin (red) within
the large ribosomal subunit (RNA, dark
green; proteins, light green). The view is
looking from the active site into the protein
exit tunnel. Erythromycin binds to the
entrance of the tunnel and blocks the
progression of nascent proteins. Source:
European Synchrotron Radiation Facility

We cannot read the popular press—let alone the scientific literature—these days without realising that the resistance of dangerous pathogenic bacteria to currently used antibiotics is increasing at an alarming rate. Methicillin (or multiple) resistant Staphylococcus aureus (MRSA) is the most talked about, closely followed by vancomycin resistant Enterococcus (VRE) as well as multiple and extremely resistant Mycobacterium tuberculosis (MDR and XDR), but many clinicians see drug resistant Gram-negative respiratory pathogens as an even bigger threat, especially to immuno-compromised patients. It is commonly believed that Nature revealed all her valuable antibiotics after the Golden Age of antibiotic discovery that tailed off after the 1960s. Drug companies then turned to robotic or combinatorial chemistry in the 1990s to fill the gap, but the tens of thousands of novel molecules synthesised by this approach turned out not to be "druggable." A promising route to improved antibiotics is to do complex medicinal chemistry by genetics—combinatorial biosynthesis—exploiting the flowering of the genetic understanding of natural product biosynthetic pathways in the late 1990s, but this is unlikely to generate novel chemical classes of antibiotics.

Alternatively—another product of the current explosion of genomic data for antibiotic producing microbes, especially for the actinomycetes, is the realisation that they encode the capacity to produce a vast array of interesting chemical entities that are not seen under typical laboratory screening conditions. Presumably these pathways have evolved to serve specific roles in the life of the organisms in their natural habitats, and they are expressed only under special conditions of the physical, chemical or biological environment of the soil. How can we wake up these "sleeping" genes and reveal the molecules that the pathways generate?

Talmudic Question #33

Imagine that we could completely get rid of the microbial biofilms found on all natural surfaces, including rocks and soil particles in and out of water. I don’t mean by scrubbing each one with a brush, but by some equally implausible process. What would be the consequences for the biogeochemical cycles of the planet?

Complex Simplicity

We translate and offer a post from the Spanish blog Esos Pequeños Bichitos (Those Small Bugs).

Bernini’s baldachin (aka canopy of state)
in the Vatican’s Basilica of Saint Peter.
The helical columns remind us of the
helical rails that transport proteins along
the membrane of bacterial cells. Credit:
Thiago.

by Miguel Vicente

The textbooks we used in the 20th century described bacterial division with one term, binary fission, implying a simple process. Nothing could be farther from the truth. Today we know that more than a dozen proteins are employed to make the division septum in Escherichia coli. They assemble in a complex sequence and all are needed. In the absence of any one, subsequent assembly is not possible and division cannot take place. Before this machinery can be assembled, an initiator protein, FtsZ, becomes localized in the middle of the cell, where it makes a constriction ring.

The Search for the Center

There are at least two mechanisms that ensure the precise location of FtsZ. One is that this protein does not function in the vicinity of the nucleoid (termed “nucleoid occlusion” by Conrad Woldringh). The other way is independent of the nucleoid and relies on the local concentration of an FtsZ inhibitor called MinC (a mechanism proposed by Larry Rothfield).