Moselio Schaechter


  • The purpose of this blog is to share my appreciation for the width and depth of the microbial activities on this planet. I will emphasize the unusual and the unexpected phenomena for which I have a special fascination... (more)

    For the memoirs of my first 21 years of life, click here.

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« February 2012 | Main | April 2012 »

March 29, 2012

Fine Reading: Autophagy & the Cytoskeleton—New Links Revealed By Intracellular Pathogens

by Elio

Life inside cells of the immune system presents a special challenge to pathogenic bacteria. Some are killed after being taken up, others survive. One favorite mechanism used by Shigella, Listeria, and Rickettsia, among others, is to escape from the phagocytic vacuole into the cytoplasm. This avoids the action of enzymes from the lysosomes that would otherwise fuse with the bacteria-containing vacuole. Once in the cytosol, the invaders enjoy what seems to be a rich and carefree existence.

But how do they infect new host cells? Instead of simply sitting idly, these bacteria recruit host actin, which in polymerizing pushes them around. When the moving bacteria hit the host cell membrane, they enter into protrusions that can penetrate into an adjacent cell. This has been the conventional story. The bug wins, or so it would seem. What does the host cell do about it? It has been discovered recently that the cells respond to these gymnastics by encasing the bacteria in cages of a cytoskeletal protein called septin. Now the bacteria can be dealt with by the autophagy system of the cell. The choreography between host and parasite continues.

One of the most satisfying aspects of current day Microbiology is how studying pathogens has contributed to our understanding of the host cell. Just like phages have helped understand bacteria, mammalian pathogens have helped elucidate the inner workings of their host.

March 26, 2012

TB or not TB?

by Jaime Zlamal, Andy Cutting, and Steven Quistad

Microfluidic

Microfluidic device used in the study. Media flows
through the main channel (large arrow) and provides
nutrients (cyan circles) by diffusion (small arrows)
to the cells. Source.

As one would expect, creating a functional human body with 10 fingers and 10 toes from a single cell is a highly coordinated process of cell differentiation. By comparison, the growth of a single rod-shaped bacterium and its division into two cells would be expected to be relatively simple. A bacterial cell elongates until it reaches a specific length, then proceeds to septate at the center, and there you have it—two daughter cells. Easy stuff, right? However, it turns out that the two daughter cells are not always the same. Cells of members of three large and anciently-diverged clades of bacteria (Actinobacteria, Alphaproteobacteria, and Planctomycetes) grow from a single pole and divide asymmetrically, producing two daughter cells that are not identical at birth. Of course, this is also the well-known lifestyle of budding yeasts.

What types of evolutionary advantages might result from creating two different daughter cells? In Caulobacter crescentus, a stalk formed at one of the poles attaches the cell to surfaces, whereas a flagellum is formed at the other pole, making that cell motile. Reproductive asymmetries may prove advantageous in removing damaged or old cellular machinery from the population. By segregating the “old” macromolecules into one daughter cell and forcing the other cell to generate new macromolecules, bacterial lineages may be able to persist under stress conditions. In these instances, polar growth creates a heterogeneous population which could increase the fitness of a microbial species in response to environmental stress. It makes sense, therefore, to look for growth at the poles in other species as well. The question arises: could polar growth also contribute to an antibiotic resistant phenotype?

Continue reading "TB or not TB?" »

March 22, 2012

The Two Quantitative Steps in the Biology Growth Curve

by Elio

Growth_curve

The early tools of the exercise: the first one-step growth curve
from the 1940 paper by Max Delbrück, obtained using B. coli and
an unspecified phage. Source.

We are witnessing a highly influential influx of physicists, mathematicians, and engineers into biology. This is not the first time. Over the centuries, biology has been blessed by the involvement of people from other fields. During the last half century or so, we can point to two distinct incoming waves, each one bringing in many with different viewpoints and often greater quantitative skills. The first wave took place after World War II and played a key role in the development of modern biology. The second one is happening now.

In brief, I would like to compare these two episodes not as a historian, but, perhaps naively, simply as one who has lived through these periods. I started my graduate work in 1950, about the heyday of the development of molecular biology, and I am still around to observe what is happening now.

Continue reading "The Two Quantitative Steps in the Biology Growth Curve" »

March 19, 2012

Sex to the Rescue

by Elio

Fig. 1 Sulfolobus_1

Fishing for hyperthermophiles. Rabbit Creek, Yellowstone
National Park. Image courtesy of Dr. Ken Stedman. Source.

Life is tough out there. If chemistry (via oxidizing radicals) doesn’t get you, sunlight (via UV irradiation) will. No wonder that cells, both prokaryotic and eukaryotic, have an intense preoccupation with keeping their DNA intact. In most organisms, a considerable portion of the genome is devoted to making sure that this actually takes place. There are two good ways to do this. One is to repair damaged DNA, the other to re-acquire undamaged DNA from undamaged cells by homologous recombination. The two are biochemically the same process, varying only in the context of how they are used. But for prokaryotes to acquire undamaged DNA from another cell, donor and recipient cells must conjugate, and that doesn't grow on trees. To make sure that it takes place with some frequency, some archaea have evolved a neat intracellular signaling system. The punch line is that they respond to UV irradiation by activating their cell-cell conjugation system.

Continue reading "Sex to the Rescue" »

March 15, 2012

Fine Reading: Nematodes & HGT

by Elio

The larger the catalog of sequenced genomes, the greater the chance for seeing horizontal gene transfer (HGT) in action. Although reports of HGT between prokaryotes and eukaryotes have appeared sporadically, it seems that incontrovertible evidence is only beginning to appear now. Indeed, the genomes of nematodes reveal that genes have been acquired from bacteria a number of times. A recent, one-page review of this subject discusses examples of this phenomenon.

Evidence for inter-domain HGT seems to be on its firmest footing when it comes to nematodes. Given the intimate contact between bacteria, fungi, and many soil-dwelling worms (many of which are bacteriovores), this should not be surprising. Nor is it unexpected that the genes that have been transferred encode enzymes that can break down otherwise indigestible sugars, such as glycosides and cellulose, that are constituents of plant food that the worms ingest. Little is known as yet about how the foreign genes “adapt” to their new genomic context, although it is known, at least in some cases, that they are indeed expressed. I can predict with confidence that this subject will be fertile territory for many years to come

Given that HGT provides endless opportunities for evolution, the question begs: Why does it not take place more often between prokaryotes and eukaryotes? Aren’t prokaryotes and their viruses a nearly endless repository of potentially useful genes? This grandmother of Talmudic Questions brings up the stark fact that organisms must be highly selective in what foreign genes they allow into their genome, lest they lose their identity and potentially their survival skills. But even without getting into the thicket of mechanisms designed to stabilize genomes and keep them from going astray, I still wonder why HGT between prokaryotes and eukaryotes (in either direction) appears to be something that may happen with some frequency but that is only rarely triumphant.

March 12, 2012

Salmonella’s Exclusive Intestinal Restaurant

by Elio

Fig_4_tetra

Transmission electron micrographs of S. enterica
strains grown on ethanolamine as carbon and
energy source. The arrow points to one carboxy-
some-like structure termed a metabolosome. Source.

Interesting, how we get carried away by exciting concepts. I am thinking about how the study of pathogens has focused so much on the microbes’ virulence factors, by which we mean nasty substances such as toxins, adhesins, and invasins that participate directly in the disease process. Their study has dominated microbial pathogenesis for many decades. Without doubt, understanding how they function is essential, but in the process we may have tended to overlook an obvious fact: for survival, pathogens have to find nourishment in the body of the host. Let’s make a distinction here between broad nutritional strategies that are common to many bacteria, pathogenic or not, and those that are quite specific to pathogens. We can expect pathogens to have evolved their own individual kind of metabolism matched to conditions in their host. A widely known example that comes to mind is the way many bacteria have invented systems to enhance the supply of iron within the host. But there is much more to this. Food for thought, no? An enlightening manifesto was published recently with the challenging title Are Pathogenic Bacteria Just Looking for Food? Metabolism and Microbial Pathogenesis.

It's obvious that animal hosts are full of goodies that microbes can readily utilize. Our bodies are replete with small molecular weight compounds such as amino acids and sugars, and our macromolecules can be cut to size by the microbes’ extracellular enzymes. But if this simply led to a feeding frenzy, there would be little in it for the pathogens, as the commensals would do just as well. Here I will discuss a particularly interesting case of a specific metabolic strategy evolved by one of the best studied of all pathogenic bacteria, Salmonella.

Continue reading "Salmonella’s Exclusive Intestinal Restaurant" »

March 08, 2012

Talmudic Question #85

If small microbes tend to be eaten by bigger ones, why aren’t all microbes big?

 

Pictograph

by Elio

Recently I saw this 600 or so year-old Native American pictograph on a large boulder in Idyllwild, CA. What do you make of it?

Picto dna sm

  

March 07, 2012

TWiM #28: Not unorganized bags of enzymes

Hosts: Vincent RacanielloElio Schaechter, and Michael Schmidt.

On episode #28 of the podcast, Vincent, Michael, and Elio review how competition within a host drives virulence of Streptococcus pneumoniae, and the expanding universe of the bacterial cytoskeleton.


Right click to download TWiM #28 (53.5 MB, .mp3, 77 minutes).

Subscribe to TWiM (free) on iTunesZune Marketplace, via RSS feed, by email or listen on your mobile device with the Microbeworld app.

Links for this episode:

Send your microbiology questions and comments (email or mp3 file) to twim@twiv.tv , or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twim.

 

March 05, 2012

How to Reform a Resistant Bacterium

by Merry

Futile
Source.

A recent paper by Edgar and colleagues captured my attention with a new twist on how to combat antibiotic resistance: Our overall goal in this study is to provide a proof of principle for a genetic system that is able to restore drug sensitivity to drug-resistant pathogens residing on hospital surfaces. And these researchers propose using my favorite life form, bacteriophages, to do the job.

The seed of their idea goes back to a 1951 paper by Lederberg. He reported that in heterozygous diploids of E. coli K-12, the wild-type (wt) allele conferring streptomycin sensitivity is fully dominant to mutant streptomycin resistant alleles. This suggests that if you introduce a wt sensitive gene into a resistant bacterium by any method, you would then have a streptomycin sensitive bacterium. You don’t even have to eliminate or alter the resident resistant gene. However, once you have such a bacterium, you need to provide some selection pressure that favors it over the antibiotic resistant multitude.

The Edgar team saw this as a potential mechanism for reversing the rising tide of antibiotic resistance, especially as manifested in the form of multiple-drug resistant nosocomial infections. Resistant bacteria can survive for extended periods on hospital “touch surfaces” from where they can be transported, directly or indirectly, to their next host. The researchers envision using temperate phages sprayed on these surfaces to introduce the genes to reform their hosts. Could this work? In their paper, they provide proof of principle for such a system.

Continue reading "How to Reform a Resistant Bacterium" »

March 01, 2012

Onboard a Flying Syringe

by Merry

MDN1-WHITEFLY_FACE__942979c

The face of a rugose spiraling whitefly in southern
Florida. This particular species recently hitchhiked
to Florida on people or plants traveling from Central
America. Although whiteflies feed on plant phloem,
the greatest impact on crop plants caused by many
species is due to their vectoring numerous viral plant
diseases. Source.

Each year we spend vast sums of money trying to obliterate an enormous number of insects. Some are targeted because they munch on plants we want to eat ourselves, others just because they have the audacity to want to share our homes with us. Our greatest concern, however, lies with those that vector pathogens, including many viral pathogens. These “flying syringes” ferry from host to host, a particularly easy task given the concentration of hosts in monocropped fields, feedlots, and cities. We’d like to be able to query these insects, ask them what hosts they have visited and which viruses they have onboard, either internally or on their surface. Now we can do just that using vector-enabled metagenomics (VEM).

Continue reading "Onboard a Flying Syringe" »

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  • We welcome readers to answer queries and comment on our musings. To leave a comment or view others, remarks, click the "Comments" link in red following each blog post. We also occasionally publish guest blog posts from microbiologists, students, and others with a relevant story to share. If you are interested in authoring an article, please email us at elios179 at gmail dot com.

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