Small Things Considered

Talmudic Question #74

by Welkin Johnson

Do the seven strategies in the Baltimore scheme of viral replication represent all possible ways of being a virus? Have other strategies fallen by the evolutionary wayside?

Coping with Hard Times: Death as an Option

by Elio

First, some musings about life and death, two matters that don't seem to occupy the same space in our brain. We tend to celebrate the former and resent the latter, and we often see the world through this perspective. Only on reflection do we realize how wrong this is, especially with regard to biology. The cycle of life depends fundamentally on living things dying. But this is not  always the prevailing way we approach biological questions. Think of how long it took for the concept of apoptosis (in itself an old realization) to take hold. In microbiology, most of the early modern studies on bacterial physiology dealt with growth and seldom with how bacteria deal with adverse conditions, such as starvation, and death. But all this is changing, as we realize that organisms have evolved to cope as much with danger as with good times. And their coping is often due to a collaborative effort, which is why the adaptation to hard times is a primary concern of the emergent science of Microbial Sociology.

Among the big-time adjustments in our views of the microbial world has been the recognition in the last few decades that bacteria do not particularly behave as individuals. That was the preferred way of thinking about them, not the least because it made life simpler. Remember that modern biology (the post-World War II variety) was greatly influenced by physicists, who brought along a  predilection  for simple units as model systems (e.g., a single atom, ergo a single T4 coliphage particle or one E. coli cell). As is now obvious, this is an incomplete way of thinking because bacteria interact in important and diverse ways with members of their same or other species. So intricate are these interactions that bacteria are beginning to vie for sophistication in communication with the social insects. Remember, both speak a chemical language.

Of Terms in Biology: Millisievert

The Fukushima nuclear power plant in better
days. Source.

by Elio

Reports in the media of the nuclear plant disasters in Japan often cite the amount of radioactivity released in units called millisieverts. Not knowing what a millisievert is, I resorted to Wikipedia for the needed clarification. We reproduce some of their explanation here as a public service.

The sievert (symbol: Sv) is the SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to the physical aspects, which are characterised by the absorbed dose, measured in gray. It is named after Rolf Sievert, a Swedish medical physicist renowned for work on radiation dosage measurement and research into the biological effects of radiation.

Six Questions About CRISPRs

by Merry

Sitting ducks. Source.

Phage predation on bacteria is intense, but bacteria are not defenseless sitting ducks. They make use of a repertoire of diverse strategies to stay even with even the wiliest of phages. First line defenses are those that block phage entry at the door. Often these involve modifying a surface component that is used by the phages as a recognition, attachment, or entry site. Such changes typically carry fitness costs, by impacting essential transporters for example; as a result, phage sensitive strains often outcompete the phage-resistant mutants when there are no phages around. Also, when resistance is gained by modifying the bacterium's surface LPS or O-antigen, acquiring resistance to one phage can mean the loss of resistance to another.

CRISPRs, on the other hand, are a second line phage defense, one that swings into action after the phage has successfully attached and injected its genome into the cell. Although it may be risky letting the wolf in the door, a successful CRISPR defense offers several advantages. For one, the bacterium may get a nucleotide lunch; for another, CRISPRs can defend against plasmids, too. And as we'll see, this system allows for resistance to multiple phages without apparent fitness costs. So far CRISPRs have been found in approximately 40% of the sequenced bacterial genomes, but that number may be an underestimate as many of the sequenced strains, having been maintained in phage-free culture for a long time, may have lost their CRISPRs.

What is a CRISPR?
For the basic story about these Clustered Regularly InterSpersed Palindromic Repeats, as known three years ago, check out our earlier post and refer to the figure legend below. For excellent recent review articles, click here, here, and here.

A CRISPR locus in a bacterial chromosome. The locus includes an array of alternating spacers and palindromic direct repeats. The identical repeats range between 21 and 47 bp in different loci; the spacers are of constant length but are hypervariable in sequence, their sequences having been derived from previously encountered DNA phages or plasmids. The entire array is transcribed as a single mRNA under the direction of a promoter located in the leader sequence. Other CRISPR-associated genes (CAS genes) encode the CAS proteins that add new spacer-repeat pairs, process the CRISPR transcript, and cleave the recognized foreign DNA. Source.

Microbial Embraces

by Elio

A Schistosoma mansoni pair, with the
thin female located in the male's so-called
gynaecophorical canal. Source.

There are embraces and there are embraces. Some may last for a lifetime, as was thought to be the case with some schistosomes (though it turns out that a few pairs do get a divorce). Other contacts, as with humans, may become quite intimate and lead to the transfer of biological material. In the bacterial world, embracing has been thought to be limited to conjugation, an iffy process that can be interrupted by shaking. But herein lies the news.

Recently, a group of researchers reported that Borrelia, the agents of Lyme disease and recurrent fever, undergo a very intimate sort of embrace. They reported seeing Borrelia cells associating, sometimes for seconds or even minutes, before again dissociating. Details of the process  as observed by using cryotomographic electron microscopy revealed something novel:  the fusion of the outer membranes of these cells (being Gram negative, they have an inner and an outer membrane). Since the fused regions span several micrometers, the two partners come to share a common periplasm. The flagella, which in spirochetes are bundled and lie within the periplasmic space, here fused to make a single bundle. And in one striking example (their words), the cytoplasms of the two cells were also seen to have fused together.

Cyanobacteria: Growing a Green Future Around the Clock

by Spencer Diamond and Britt Flaherty

Cyanobacteria, present as stromato-
lites, oxygenate the atmosphere of
earth in this artist's representation.
Source.

With such famous bacteria as Escherichia coli and Bacillus subtilis hogging the stage, it can be hard for bugs like cyanobacteria to enter the limelight. However, without E. coli and B. subtilis we would still be here today; without cyanobacteria (or something with similar capabilities) earth would be an anaerobic world incapable of harvesting the sun's energy. Cyanobacteria infused the atmosphere with oxygen, provided photosynthesis to plants through endosymbiosis, and increased the amount of usable nitrogen by fixing atmospheric N₂ into ammonia. Many of these little photosynthetic factories can undertake conflicting metabolic processes within a single cell, such as photosynthesis and nitrogen fixation. With the need for renewable sources of energy and industrial products, cyanobacteria present themselves as an excellent self-contained platform for metabolic engineering and subsequent green chemical production.

The open ocean accounts for roughly 20% of all biological nitrogen fixation on the planet, and most of that  is the work of cyanobacteria and their nitrogenase enzyme. The oxygen-sensitivity of nitrogenase, however, poses a key problem: how does one fix nitrogen while living in an aerobic environment? Moreover, both photosynthesis and nitrogen fixation require iron, an extremely limited resource in open ocean environments. The cyanobacteria found ways to separate nitrogenase from oxygen, both physically and temporally, and some even coordinate this separation for efficient iron utilization.

Beyond the Bacterial Microcompartment

by Merry

A spectrum of compartments and enzyme complexes. (A) Model
of the ethanolamine utilization (Eut) microcompartment. (B)
Model of the carboxysome microcompartment. (C) Shell
structure of T. maritima encapsulin. (D) Shell structure of
B. subtilis lumazine synthase. (E) 3D reconstruction of
bovine pyruvate dehydrogenase complex. (F) Structure of
human ferritin. Source.

Bacterial microcompartments were a great innovation. As Alan Derman explained,  these protein-bounded structures assist with diverse metabolic processes by housing the requisite enzymes along with their substrates, sequestering potentially toxic intermediates, and allowing the products to exit. But the story does not end there. Enter the nanocompartment.

These are the simplest variation known so far on the theme of bacterial compartments. Like the micro version, these nano structures are thin, icosahedral protein shells that enclose a specific protein payload. Here the shells are only 20-24 nm in diameter, compared to the ~120 nm diameter of the microcompartments, and the shells are built from only 60 copies of a single protein, encapsulin. Turns out that the encapsulins are a large and widely-distributed family of proteins found in both the Bacteria and the Archaea. The first ones had been noticed a decade ago in culture supernatants of Mycobacterium tuberculosis and Brevibacterium linens. However, their structural role in the building of protein shells was not discovered until 2008 when Sutter and colleagues investigated the structure of the capsulin of Thermotoga maritima, a hyperthermophile from a very deep branch in the bacterial lineage. (For a helpful commentary on the Sutter paper, click here.)

Pneumococcus: Nature’s Tiniest Cheat

by Brandon Kim and Jon Sin

To a pathogenic microbe, the human body is a foreboding environment filled with bacteriocidal immune cells ready to seek out and destroy foreign invaders. When a leukocyte detects the presence of pathogen-associated molecular patterns (PAMPs) present on the surface of pathogenic bacteria, it releases an array of cytokines, mounting an immune response and bringing about an abrupt end to the pathogen’s colonizing campaign. However, as a testament to bacterial evolution, many species of bacteria have developed tactics to evade the host immune system. Such trickery includes hiding within the safety of host cells, releasing free antigens into the blood to inactivate antibodies, or coating themselves with a slippery sugar-based capsule that makes them inedible by macrophages.

One method employed by the meningococcus (Neisseria meningitides) and H. flu (Haemophilus influenzae) is to cover their surface antigens with sialic acid, a monosaccharide that is widely found as a terminal residue on the polysaccharides that coat the cells of our tissues. In this way, these pathogens disguise themselves as "self," thus thwarting the action of patrolling leukocytes. Truly, this would seem to be a foolproof method of immune evasion, as patrolling immune cells would be none the wiser, allowing the invading bacteria to comfortably colonize the respiratory tract free from danger. And indeed, this tactic does effectively ward off immune attacks, but it does not evade a most-conniving cohabitating organism, the pneumococcus (Streptococcus pneumoniae).

Talmudic Question #73

Note:  Please note today's date.

If people go to heaven does their microbiome go with them?

Ramy Aziz, Merry, and Elio already provided some imagined responses.

An answer from Rome:  Only microbes that don't engage in immoral horizontal gene transfer or illegitimate recombination.

A moralist’s answer:  Each microbe will be judged by her actions. Did she produce more energy than waste products?

A Jewish answer:  Why not?

A Protestant answer:  Depends on their denomination.

A Hindu answer:  Better sequence the microbiome's genomes in order to detect changes upon reincarnation.

A Taoist answer:   Host and microbiome are equal in the eyes of the Tao. The ten thousand things are all manifestations of the Tao.

A Pantheist answer:  Only pangenomes get in.

The Microbiota's answer:  Aren't we there already?