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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April 03, 2014

The “Microbe Hunters” by Paul DeKruif - A Major Force in Microbiological History

by Elio

The chances are good that when you ask a senior microbiologist how he or she got into this science, they will tell you that they were influenced as teenagers by reading  “Microbe Hunters.” I was about 14 years old when I did, and I became transfixed by the glorious and intrepid achievements of our forefathers, told in a jaunty and florid style. There was nothing else I wanted to do with myself than to become a Microbe Hunter.

Figure1 Figure 1. Microbe Hunters (1950 edition)

This book was written in 1926, two years before my birth, by the microbiologist Paul DeKruif, whose career was as checkered as it was unusual. He graduated in 1916 from University of Michigan with a PhD in microbiology and, after World War I, got the job at the Rockefeller Institute. This, however, did not last long because his lifestyle included writing for the general public, which at the time was frowned upon by the establishment. He also hung out with such suspect characters as Carl Sandburg, H.L.  Mencken, and Sinclair Lewis, of whom he became a welcome drinking companion. DeKruif became the source of microbiological information for Lewis’ best-selling book, Arrowsmith. In this book, a somewhat persecuted microbiologist works on developing phage therapy in a lab he had built in his own home.

Figure2 Figure 2. Paul DeKruif. Source.

”Microbe Hunters” rapidly became a huge success. It was translated into all major languages and inspired two Hollywood movies. It still sells well. But for all its appeal, it received serious criticism. DeKruif wrote in a “jazz style,” where bravura at times seems to be more important that the facts. To make the narrative conform to his “voice,” DeKruif not only made up dialog from whole cloth but also took liberties with the facts.  So much so that one of the people depicted in the book, the British microbiologist Ronald Ross, threated a lawsuit. The matter was resolved by omitting the chapter on Ross from the British edition! But such thorny facts do not detract from the impact of the book. As I can attest, if you read it at a susceptible time of life, you will be carried away by the pungency of the tales, the spirited portrayal of the protagonists and the glory of the achievements.

For more on the book and its author, click here for an article by Robin Marantz Henig and here for a video clip of a lecture by John M. Lehman.

March 03, 2014

A Mouthful Of Microbes

by Gemma Reguera

Smile (or not)!

Figure1 Figure 1. One of our ancient relatives? Source.

After watching Hollywood movies of medieval knights with neat haircuts and bright smiles, it may shock you to be reminded that our dear medieval cousins looked anything but clean. The truth is that hygiene was not a top priority in the Middle Ages and germs were in heaven. This was a time in which cities lacked sewage systems and feces, urine, and garbage were dumped onto the streets or into the castle moat. Not surprisingly, outbreaks of water-borne diseases were a frequent occurrence. Add to that religious concerns about nudity, and it will not surprise you to know that even the most illustrious doctors recommended not taking baths regularly. As a result, everybody, from the lowest peasant to the most powerful king, stank like a smelly animal.

In this era of complete disregard for personal hygiene, people did pay some attention to dental hygiene. Why? Because toothache was a widespread malady and people would result to anything in their power to prevent it and alleviate it. They would rub on their teeth, for example, mixtures of fresh or burned scented herbs such as parsley, mint, and rosemary, and then rinse their mouths with solutions made of herbs, vinegar, wine, and/or alum (the latter is still use by many as a home remedy for sore throat). Alas, these practices were not effective enough to prevent dental bacteria from growing and causing cavities and infections. I also read that our medieval ancestors were advised to clean their teeth in the morning, rather than at night. I imagine this was done to ensure they had good (better?) breath. However, the morning practice left the oral microbes free to roam and proliferate throughout the long night hours. Hence, cavities and abscesses were very common and medieval barbers found a profitable side job: pulling out teeth!

Continue reading "A Mouthful Of Microbes" »

February 17, 2014

The Fungus That Killed Darwin’s Frog

by Gemma Reguera

A Mouthful of Kids

Figure1 Figure 1. A ‘pregnant’ male Darwin frog carries its babies in the vocal pouch (left) until they are big enough to be spat out (right). Sources here and here.

In his second expedition to South America, Darwin discovered many new species of animals and plants. The field observations obtained throughout this 5-year expedition provided the intellectual framework for the maturation of his ideas on evolution. It also introduced the world to a tiny (2-3 cm in length) frog known as Darwin’s frog. The group includes the northern (Rhinoderma rufum) and the southern (Rhinoderma darwinii) species, which inhabit the central and southern forests of Chile (and adjacent areas of Argentina), respectively. As in many other amphibians, fecundation is external. However, Darwin’s frogs do not leave the fecundated eggs on the ground and exposed to environmental insults and predators. The males scoop them with their mouths and incubate them in their vocal sac. The dedicated dads feed their offspring after the eggs hatch, producing secretions analogous to milk that allow the tadpoles to grow in a protected environment, sometimes until they have fully developed into froglets. When the young are mature enough to fend for themselves, the male frog literally spits them out. You can see a short video describing this amazing reproductive strategy following this link. This behavior, generally known as neomelia, allows the male ‘surrogates’ to care for the eggs and then the young, maximizing survival throughout the critical tadpole stage. Unfortunately, deforestation in the regions inhabited by these frogs has resulted in vast habitat losses, leaving Darwin’s frogs in precarious conditions. The last sight of a northern Darwin frog was reported in 1980, leading researchers to suspect that this particular species went extinct years ago. The species has been tagged as ‘possibly extinct’. The southern species, R. darwinii, which has traditionally occupied a much larger region, has been able to survive, but population numbers have declined dramatically.

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February 10, 2014

Death Toll to Persisters

by S. Marvin Friedman

Figure1 Figure 1. Persistence. Source.

The disconcerting ability of bacteria to evade death from treatment with antibiotics is achieved with two distinct strategies, resistance and tolerance. Resistance occurs by a variety of mechanisms, including drug efflux and/or preventing the drug from binding by modifying either the drug itself or its target. Tolerance, on the other hand, is a characteristic of a subpopulation of normal cells known as “persisters.” This phenomenon was first described by J. W. Bigger in 1944 who found that some members of a population of Staphylococcus aureus survived treatment with penicillin. Pathways leading to tolerance have been studied extensively in Escherichia coli, where they have been shown to be highly redundant and therefore hard to combat. At long last, the work of Lewis and collaborators suggests that a combination of antibiotics mat be the answer to this mode of bacterial defense.

Persistence Counts

Here’s how persisters arise: given that most antibiotics work on growing bacteria, slowing down their metabolism will make them insensitive to the drugs. Normally, a small proportion of cells in the population spontaneously enter a state of reversible dormancy. Commonly, this is thought to take place through the action of toxin-antitoxin modules. An example of such a mechanism relies on the activity of the HipA toxin, a kinase that phosphorylates a glutamyl-transfer RNA synthetase. This leads to the overproduction of the signaling molecule (p)ppGpp and the activation of the stringent response, which shuts down the synthesis of about 1/3 the genes of the bacterium and thereby leads to dormancy. But there are other dormancy pathways as well and their multiplicity makes finding a drug that inhibits the development of persistence a futile task. Thus, researchers have recently turned their attention to the search for agents that would “corrupt” a target in persistent S. aureus cells located within a biofilm.

Before discussing the paper in question, note that the theme of persistence has been often linked to that of biofilm formation. This is appealing because bacteria in biofilms often become insensitive to antibiotics, ergo can turn into persisters. Many chronic infections have been shown to involve biofilms, including osteomyelitis, endocarditis, deep-seated infections of soft tissues, gingivitis, infections of catheters and other indwelling devices. Particular attention has ben paid to the emergence of persisters in Pseudomonas aeruginosa biofilms.

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November 04, 2013

Radiation Ahead? Eat a Black Mushroom!

Week of the Fungi on STC is a sporadic undertaking. This occasional festival is our way to hail the fall mushroom collecting season in parts of the northern hemisphere. We are a bit late this year, but mushroom collecting is still possible in many parts.

by Elio

Fig. 1. Left: Auricularia-auricula-judae (Judas’ ear, tree ear, jelly ear). Source. Right: Boletus edulis (porcini, cep, king bolete). Source.

Suppose that one day you have the misfortune to receive a strong dose of radiation in preparation for a medical procedure, say a bone marrow transplant. To your surprise, the physician prescribes that you eat a hefty serving of dark-colored mushrooms about an hour beforehand. Lest you think this black magic, the clinician explains that this has been proven effective in 'clinical trials' in mice, surprisingly so in fact. A 2012 paper with the forbidding title Compton Scattering by Internal Shields Based on Melanin-Containing Mushrooms Provides Protection of Gastrointestinal Tract from Ionizing Radiation describes this work. The authors fed mice a mushroom used in East Asian cuisine, called Judas’ ear, tree, or jelly ear (Auricularia auricula-judae) an hour before giving them a powerful 9 Gy dose with the beta emitter Cesium137. For perspective, anything over ~0.1 Gy is considered a dangerously high dose for humans. All the control mice died in 13 days while ~90% of the mushroom-fed ones survived. Mice fed a white mushroom (porcini) died almost as fast as the controls, but those fed white mushrooms supplemented with melanin also survived.

Continue reading "Radiation Ahead? Eat a Black Mushroom!" »

October 14, 2013

Vesiculation: Another Bacterial Skill

by Elio

Microbiology, we will agree, is a vast subject where many important aspects are likely to evade one’s sight. Here’s an example—the formation of vesicles from the outer membrane of Gram-negative bacteria. This phenomenon, known as vesiculation, is widespread and noteworthy for enhancing our understanding of bacterial capabilities and for its potential applications. My guess is that many microbiologists, like myself until recently, have only a hazy notion of it.

Let me set this in context. Bacteria have evolved a panoply of tactics for communicating both socially and antisocially with most anyone, be they other bacteria or cells of their host. For this they deploy small molecules (active only above a critical threshold concentration, hence quorum sensing), they construct pili to translocate DNA, and they export proteins via more than a half dozen secretory systems. Each of these tactics requires its own mechanics and makes its own demand for energy. Secreting proteins freely into the environment is particularly wasteful of resources because few of the molecules are likely to reach their intended target. To improve the odds, some bacteria depend on making direct contact between donors and recipients before exporting. Others parcel out the molecules inside specialized delivery structures—the subject of this post.

Fig. 1. OMVs on an enterotoxigenic E. coli recovered from mouse small intestines 2h after intragastric inoculation. EM by Amanda McBroom. Source.

Vesicles On The March

Many, possibly most of the Gram-negative bacteria produce extracellular vesicles from their outer membrane (OM). These blebs, usually called outer membrane vesicles (OMVs), are spherical structures typically 20 to 200 nm in diameter formed by the outward protrusion of small bits of the OM that then pinch off to release the vesicles into the environment. Thus formed, the OMVs are bounded by a double-layered membrane with the usual OM protein, lipid, and lipopolysaccharide (LPS) constituents, and carry within them proteins from the periplasm. While details of the mechanism of vesiculation are yet to be elucidated, here’s one exciting example: The Pseudomonas aeruginosa signaling molecule PQS (2-heptyl-3-hydroxy-4-quinolone) stimulates OMV formation, apparently by inducing membrane curvature through interaction with the LPS.

Continue reading "Vesiculation: Another Bacterial Skill" »

September 16, 2013

It’s Time for Salmonella

by Susan Golden

If one were to ask, “What happens when Salmonella infects the gut?” it might not be obvious that you’d also need to ask, “What time is it?” But indeed you’d need to know the latter to appropriately address the former. An invading Salmonella, intent on setting up camp, is trying to pitch its tent on a landscape that is changing throughout the day. The mammalian gut, like most eukaryotic and some prokaryotic cells, uses an internal timing device to control its physiological functions. The circadian, or 24-h (circa diem, about a day) clock employs an endogenous oscillator to control gene expression, metabolism, and other cellular processes in such a way that individual genes, pathways, and their components ebb and flow in activity with distinctive daily programs, meshing together to execute the enterprise of the cell. Among circadian regulated processes are aspects of the immune system, including components of the inflammatory response. Included are changes in the expression of several inflammation-related (“proinflammatory”) cytokines by macrophages not only in the animal but also ex-vivo. Not coincidentally, Salmonella thrives in the inflamed gut.

Bellet and colleagues set out to investigate the relevance of circadian rhythms of the mammalian immune response during infection by using a mouse model. In this protocol, animals are pretreated with streptomycin, overtly to rid the mouse of much of its intestinal microbiome (this is known as the “colitis model”). Pretreatment with the antibiotic changes the way the mice respond to Salmonella enterica serovar typhimurium, which would otherwise mount a systemic infection more similar to typhoid in humans. The handy mouse colitis model frees researchers from the restrictive and expensive need of using the other established model: cows. The mice pretreated with streptomycin, once infected with Salmonella, mount a massive inflammatory response in the gut, as do humans.

Figure 1. Representative images (10× magnification) of cecal inflammation in WT mice infected (Salmonella) or not at day or night. Source.

Continue reading "It’s Time for Salmonella" »

September 02, 2013

Mtb Craves Sweets

by S. Marvin Friedman

Figure 1. View of the inside of a plaster cast of the skull of a young male Homo erectus from western Turkey. The blue stylus points to tiny lesions 1-2 mm in size found along the rim of bone just behind the right eye orbit. The lesions were formed by a type of tuberculosis that infects the brain. At 500,000 years in age, represents the most ancient case of TB known in humans. Source.

Tuberculosis is an ancient disease that still affects millions of people, largely in developing countries. A startling statistic valued by fundraisers for tuberculosis research is that this devastating disease claims three lives every minute worldwide. Since a major factor underlying this important health threat is the alarming rate at which drug-resistant strains emerge, the search for new therapeutic agents is of urgent concern. The armamentarium currently available for the treatment of tuberculosis is pretty feeble and better drugs are badly needed. Favored targets for antibacterial drugs are the pathogen’s virulence factors (see for example), one reason being that the selection for resistance to such specific inhibitors should be weaker than for –static or –cidal drugs. But beyond that, to understand the infection process we need to have a thorough knowledge of the virulence factors involved and how they operate.

When it comes to the tubercle bacillus (Mtb), the detection of virulence factors has been relatively slow in coming. This organism does not make classical exotoxins, but rather, they give the impression that it is an “existential pathogen,” causing disease mainly by the reactions of the host’s immune system. Surely it isn’t that simple—the bugs are not just inert bystanders. In fact, the list of mycobacterial virulence factors is rapidly expanding to include constituents responsible for host-cell invasion, intracellular replication, escape from the cytosol, stimulation of cytokine formation, killing of host cells, and dissemination. Added to the list are novel secretory mechanisms that allow these factors to escape from the bacteria. So, progress along these lines is being made.

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August 12, 2013

Polymicrobial Infections: Perhaps The Rule, Not The Exception

by Katy Patras

Figure 1. Critically ill patients in the intensive-care unit are good examples of the diversity of sites at which bacteria and fungi can interact and cause disease. The boxes describe the organisms that are most commonly found at each site. Source.

The recent film World War Z describes an apocalyptic event where a rabies-like virus spreads via bite wounds to the majority of Earth’s population and turns them into zombies. Since the world’s leading virologist dies early in the film, it is up to Brad Pitt’s character to find the source and cure for this zombie virus. Spoiler alert: He discovers that virus-infected individuals will not bite humans with other infections or terminal illnesses, and proceeds to infect himself with a BSL4 pathogen and walk among the zombies unscathed. Although every scientist reading has first cringed and then come up with at least a half dozen reasons why this is not possible, the point is that even the film industry is recognizing that pathogenic (and non-pathogenic) microbes are capable of communicating with one another within the host to alter the course of disease.

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July 15, 2013

Aggregatibacter actinomycetemcomitans: A Unique Exotoxin-Producing Oral Bacterium

by Pedro Valero-Guillén

Fig. 1: Colony of A. actinomycetemcomitans, showing the characteristic flower-like morphology. From UCL Eastman Dental Institute. Source.

The production and secretion of protein toxins (exotoxins) is a most common strategy among microbial pathogens. Yet, oddly, these virulence factors are fairly rare among oral pathogens, with one exception, the Gram-negative Aggregatibacter actinomycetemcomitans. For readers with an interest in taxonomy, this microbe was originally named Actinobacillus actinomycetemcomitans and later reclassified and renamed (you known taxonomists...). The new genus name refers to the microbe’s tendency to aggregate with other bacteria in the dental plaque, whereas the equally bombastic species name speaks to the fact that it was isolated together with the common mouth-dwelling Actinomyces. This microbe makes pretty colonies that look like a flower. But, esthetics aside, this microbe has attributes that warrant special attention. It is found in about one third of the human population and it is involved in a particularly rapid progressive form of adolescent periodontal disease, common in those of African descent. It has also been implicated in infective endocarditis and other deep serious infections. Viable cells of A. actinomycetemcomitans cellshave been identified in atherosclerotic plaque. This is, without a doubt, a microbe that knows how to cause trouble. But what makes it so prominent in the oral environment and such a successful pathogen?

Continue reading "Aggregatibacter actinomycetemcomitans: A Unique Exotoxin-Producing Oral Bacterium " »

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