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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« August 2011 | Main | October 2011 »

September 29, 2011

One Size Sometimes Can Fit All

by Merry Youle

In 2008, a man died in a Swedish hospital from an antibiotic-resistant urinary tract infection that he had acquired on a recent trip to New Delhi. The bug responsible was a Klebsiella pneumoniae  strain that was found to harbor a new, plasmid-encoded, antibiotic resistance gene. By 2009, this antibiotic resistance factor, the New Delhi metallo-β-lactamase 1 (NDM-1), had been found in 22 carbapenem-resistant organisms, including 10 Klebsiella species, 9 E. coli strains, 2 enterobacter species, and Morganella morganii. As of late 2010, cases had been reported in multiple areas of India, Pakistan, Bangladesh, USA, Canada, China, Japan, United Kingdom, Israel, Turkey, Australia, France, Kenya, Singapore, and the Nordic countries, although most cases outside of India were still limited to persons who had visited there. What makes this particular metallo-β-lactamase (MBL) of especially great concern is that it is effective against an unusually large range of β-lactam antibiotics including our current antibiotics of last resort, the carbapenems.

The cat is out of the bag. It is doubtful that NDM-1 can be geographically contained now, and those who monitor such things are mighty worried.     Our best hope at the moment is to design an effective inhibitor that can be administered clinically along with β-lactam antibiotics. As a key step in that direction, researchers recently reported successful determination of NDM-1’s structure by X-ray crystallography. Although sharing only 20-33% sequence identity with other MBLs, it possesses the characteristic MBL ‘fold’ and has conserved key amino acids at the active site. Based on active site similarities, NDM-1 is predicted to bind two zinc ions, both of which are involved in catalysis of β-lactam hydrolysis. However, the structure of NDM-1 differs significantly from that of other known MBLs in that the active site is larger and many of the catalytic amino acids are located on five flexible loops. Both of those modifications likely contribute to NDM-1’s ability to accommodate and hydrolyze a host of structurally diverse β-lactams.

Continue reading "One Size Sometimes Can Fit All" »

September 26, 2011

A Bug in a Bug in a Bug

by Elio

Mealybug

A mealybug, Planococcus citri. Mealybugs are so
called because they’re covered with a white powdery
substance. Source.

Rattling around inside my head for some time has been the reported discovery that there are bacteria that live within other bacteria. To me, this is an honest-to-goodness gee-whiz piece of microbial lore. Made me wonder why the story had not been followed up on. Could be because you have to go to mealybugs to find these eccentrics. But now I'm happy to report that someone has. A recent paper by the discoverer of this phenomenon, entomologist Carol von Dohlen, and the endosymbiont expert John McCutcheon has the tantalizing title of An Interdependent Metabolic Patchwork in the Nested Symbiosis of Mealybugs. Note that this blog is especially receptive to the allure of parasites within parasites (the ‘nested parasites’ or matryoshka dolls). As evidence, see also other of our stories about endosymbioses with complex metabolic relationships (click here and here).

Bacteriocytes

Artificially colorized TEM of Planococcus citri
bacteriocytes. Tremblaya cells are colored dark
blue, Moranella cells are red, the mealybug cyto-
plasm is grey, and the mealybug nucleus is green.
Bar = 2.33 μm. Source.

First the players. The insect in question is the citrus pest mealybug, Planococcus citri. Like aphids and other insects that feed on the amino-acid poor phloem sap of plants, mealybugs require endosymbiotic bacteria to provide them these essential nutrients. They carry these working partners in the cytoplasm of specialized cells, the bacteriocytes. As for the bacteria, the ‘host’ is β-proteobacterium Candidatus Tremblaya princeps, called Candidatus because it cannot be grown in the lab. Its name won’t be italicized until this rule changes. It better, because T. princeps (I use italics in defiance) will never be able to grow independently as it has the smallest of all known cellular genomes: 139 kb. Living inside of it is the newly named γ-proteobacterium, Moranella endobia (also a ‘candidatus,’ but we’ll dispense with that.) The genus name honors the famed endosymbioticist Nancy Moran. The host Tremblaya cells are quite large, 10-20 μm wide; nested within are the Moranella, each 3-6 μm long and with a Gram-negative-like double membrane structure. Moranella has the audacity to possess a genome about four times larger than that of its host, a case, ostensibly, of genomic chutzpah.

Continue reading "A Bug in a Bug in a Bug" »

September 23, 2011

21 Blogs Considered

by Elio

Fellow blogger César Sánchez has posted Microbiology Blogs: A list of 20 great blogs for microbe lovers. Modestly, he omitted his own notable blog, Twisted Bacteria.

We are in good company. Thanks, César.

September 22, 2011

Fine Reading: Microbial Evolution

by Merry

Cover2

Darwin focused his attention on visible life forms…and there the evolutionary focus remained until recent decades when the microbes seized the limelight. The American Academy of Microbiology (ASM’s honorific leadership group) acknowledged this overdue shift two years ago, on the 150th anniversary of publication of On the Origin of Species. The AAM brought together 34 microbiologists with diverse specialties to participate in a colloquium held in the Galapagos Islands (where else?). What, they collectively wondered, would Darwin have made of the microbial world?

Some answers are shared in the colloquium report recently published by the AAM. For readers of this blog, already among the converted, the report provides a cogent summary of the importance of microbial evolution for all life on Earth—past, present, and future. The report’s clear and attractive presentation makes it also well-suited for use when proselytizing to those who tend to ignore The Small Things. As you would expect, it reminds us that for billions of years, microbial evolution was the only evolution, and that today most of the extant biological diversity is microbial. Further, it points out that many of the mechanisms driving the evolution of both macrobes and microbes were discovered by studying the latter. Studying microbial evolution is also useful in a practical sense as we seek new ways to tailor microbes for our own purposes (e.g., controlling disease, biosynthesis of useful materials, bioremediation). Despite methodological advances, these studies remain challenging due to the vast diversity of the microbes, their rampant gene swapping, and their ability to adapt at both the individual and community level.

This research takes on an added importance today because of the key role of the microbes in modifying and maintaining the global systems that support life on Earth. As we go purblindly about perturbing environmental systems in countless ways, some are asking: How resilient are these systems? How will the microbes respond? In the tradition of these colloquia, the report concludes with well-founded recommendations for how to pursue the answers. Key current research questions are highlighted, as well as potentially fruitful research directions. In brief, the report reminds us that if you want answers to such questions, ask the microbes.

September 19, 2011

Bacteria Activate Fungal Gene Clusters

by S. Marvin Friedman

Structure

Legend: Orsellinic acid. Source.

Fungi are notorious for their ability to produce a wide variety of secondary metabolites, including antibiotics, statins, immunosuppressants, mycotoxins, and others. A veritable pharmacopeia. Interestingly, many of the gene clusters involved in the biosynthesis of these compounds are silent under normal laboratory conditions. In some cases, the synthesis of these compounds is known to depend on a symbiotic relationship with bacteria. Previous research has shown that intimate physical contact between the model fungus Aspergillus nidulans and the soil bacterium Streptomyces rapamycinicus activates the fungal ors gene cluster that encodes one of the fungal secondary metabolites, orsellinic acid and its derivatives. The effect is impressive: gene expression is 5 orders of magnitude greater when the fungus and bacterium are co-cultivated. Orsellinic acid is a polyketide, a large group of organic compounds that include antibiotics such as erythromycin, tetracyclines, and amphotericins. Orsellinic acid has pharmacological activities, including radical scavenging.

In filamentous fungi, the regulation of secondary metabolism involves the post-translational modification of histones. Nutzmann and coworkers have now analyzed the effect of several such epigenetic modifiers on the synthesis of orsellinic acid by A. nidulans co-incubated with S. rapamycinicus. Adding an inhibitor of histone acetyltransferase (HAT), lecanoic acid,  blocked transcription of the orsA gene. On the other hand, a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, activated the orsA gene without the need for co-incubation with S. rapamycinicus.

Continue reading "Bacteria Activate Fungal Gene Clusters" »

September 15, 2011

Talmudic Question #79

What's your guess as to the number of different kinds of viruses that can infect a single species on average?

September 12, 2011

Wolbachia: The Difference Between a Nuisance and a Threat?

by Jamie Schafer

N_vitripennis

The parasitoid wasp N. vitripennis is a Wolbachia
host in which the degree of cytoplasmic incompati-
bility correlates with bacterial density. Credit: Oliver
Niehuis. Source.

No summer evening outdoors seems complete without a mosquito bite (or ten). While these bites are often just a nuisance, they can also serve as the point of transmission for many mosquito-borne diseases: West Nile virus, dengue virus, yellow fever virus, malaria, and the filarial nematodes that cause elephantiasis, to name a few. Efforts to control the spread of these diseases, many of which cannot be curbed by vaccination, have lately looked to the intracellular bacterium Wolbachia pipientis for help. Wolbachia naturally infect many insects including some mosquitoes, and strains have recently been developed to infect Aedes aegypti, the vector for dengue, and Anopheles gambiae, malaria’s vehicle of choice. Infection by Wolbachia may limit the spread of these diseases by efficiently becoming established in insect populations, where they shorten the lifespan of their hosts or directly interfere with the pathogens the insects carry.

With virions wasp_testes_2

Wolbachia infecting the testes of the wasp N. vitri-
pennis.
Arrowheads = phage particles inside Wol-
bachia.
Field of view ~0.6 μm wide. Adapted from
this source.

Wolbachia spread very effectively through insect populations. For example, when researchers released infected A. aegypti mosquitoes into a wild population, nearly all mosquitoes in the population became infected in just a few months. This efficiency is due largely to a phenomenon called cytoplasmic incompatibility. Upon Wolbachia infection, dramatic changes occur in the host insect’s gametes such that infected females can reproduce by mating with either infected or uninfected males, but uninfected females who mate with infected males have no offspring. Since the bacterium is passed on maternally from infected females to their eggs, this incompatibility gives a reproductive advantage to infected females, thereby favoring the spread of Wolbachia. Although its cause has remained somewhat elusive, the degree of cytoplasmic incompatibility correlates with bacterial density. Recently it was also shown to inversely correlate with infection of the Wolbachia with bacteriophage WO-B in the parasitoid wasp Nasonia vitripennis. WO-B lytic development would cause lower bacterial density, and may  explain how WO-B infection causes differences in the strength of cytoplasmic incompatibility observed in some Wolbachia strains.

Continue reading "Wolbachia: The Difference Between a Nuisance and a Threat?" »

September 08, 2011

Fine Reading: Two Fine Protist Blogs

by Elio

Ocelloid

Merry and I would like you to know about two specialized blogs that deal mainly with protists, one called Skeptic Wonder, the other The Ocelloid. The first one is a spirited blog whose history goes back to 2008, the second a recent addition to the Scientific American Blog Network. Both are written by a friend and avid protistologist who goes by the name of Psi Wavefunction, and we’re glad to help publicize them.

We applaud the blogger's effort, in good part because we believe that protists need good press. Everyone has heard of them, perhaps encountering them as pond-scum paramecia in high school, when learning about malaria, or more recently in the hoopla about using micro-algae to produce fuels. But they deserve more attention than that for their enormous variety in shape, size, and genomic complexity. They have a central role in this planet’s metabolism, being responsible for a huge amount of carbon cycling. In addition, many, like the diatoms, are a joy to the eye.

The first issue of The Ocelloid is A Quick Dive into the Protist World, and quite a trip it is. Here you'll encounter organisms you may have heard about, or not—intricate radiolaria, filose amoebas that leave tracks on the sand, and gorgeous foraminifera. The name of this blog refers to an eye-like structures of dinoflagellates, the ocelloid. This is a true model biological wonder, with a complexity that approaches that of the vertebrate eye, all in one unicellular organism.

Many blogs deserve your attention, but these two stand out in our opinion.

Skeptic

 

September 05, 2011

Phage DNA: Going with the Flow

T4s on coli

Phage T4 virions poised on the surface
of an E. coli cell. Courtesy of Cornell
Integrated Microscopy Center. Source.

by Merry Youle

We've heard it said so often, it must be true. After tailed phages adsorb to their host and bind securely to their specific receptor on the cell surface, they inject their DNA into the cell and the infection is off and running. This injection notion arose naturally from the classic image of a T4 phage with its contractile tail, poised syringe-like on the surface of its soon-to-be host E. coli. The tail contracts, the DNA squirts into the cell. Simple, but is it true? In particular, it leaves us asking where the force that moves the DNA comes from.

T4_DNA

A classic dark field image of the DNA molecule released
by rupture of a single T4 capsid. (Two other intact
virions are also shown.) Source.

A popular answer invokes the pressure inside the phage capsid, and that pressure is not negligible. The DNA within a T4 virion is estimated from indirect measurements to exert a pressure on the capsid of about 60 Atm, the result of being packaged at very high density (on the order of 500 mg ml–1) and confined in tight quarters against its will. The double-stranded DNA (dsDNA) of phage T4, for example, is about 50 μm long, whereas its capsid diameter is only about 1/1000 of that (85 nm). Tightly coiled inside the capsid, the DNA double helix pushes back due to its inherent bending resistance and the mutual repulsion of its negatively-charged phosphate backbone. Stuffing all the DNA into the capsid in the first place, against ever-increasing resistance takes work. The DNA 'packaging motor' of phage φ29 can move its DNA into a capsid against a force of at least 100 pN (whereas molecular motors such as dynein and kinesin exert a force of only 5-7 pN).

Continue reading "Phage DNA: Going with the Flow" »

September 02, 2011

How to Escape a Deadly Embrace

This is the last of three installments celebrating the Week of the Fungi on STC.

by Elio

1st_screen

A network of fungal hyphae modified for nematode-
trapping. Source.

The space around a single soil particle can be one hell of a battlefield. Here, nematode worms consume bacteria, bacteria fight back and kill them, fungi suck the worms dry, and so on. Not a moment of peace. These battles are as intense as they are intricate, yet we know little about all this drama. Honest, if it weren’t for C. elegans, nematodes would hardly be in my consciousness despite their enormous abundance and ecological importance in soils and waters. They are found nearly everywhere. They are major players in the McMurdo Dry Valleys of Antarctica, and have recently been found one kilometer down in a gold mine, where they feed on bacterial biofilms growing on the walls. Nematodes have their bard: a delicious 1914 article by N.A. Cobb graciously extols their glory. But this being Fungus Week at STC, I choose to relate a nematode story of life in the soil that involves fungi.

Continue reading "How to Escape a Deadly Embrace" »

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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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