One simple medical test for all infections

21 05 2015

University of Toronto researcher uses new technology to fast-track diagnoses and provide targeted treatment


The technology will be ready for clinicians to use for routine testing in about a year, says Samir Patel (photo by Gerda via Flickr)

If you’re returning from abroad with a fever, your doctor will likely test you for malaria. You’ll give multiple blood samples at the lab, and if the results are inconclusive, you’ll face yet another round of tests.

But researchers from the University of Toronto are fast-tracking this process with new technology. With one sample, they can quickly and accurately diagnose a patient and recommend targeted treatment against any bacteria or virus.

“With this new technology we can streamline ordering 30 different tests. We can just order the one test and identify the pathogen – whether it’s dengue fever, West Nile virus, Chikungunya virus, or a new bacteria or virus,” said Samir Patel, a professor at U of T’s department of laboratory medicine and pathobiology.

Using what is called Next Generation Sequencing, Patel takes a patient’s sample and analyzes its genetic code. His team then matches the code to a database of thousands of bacteria and viruses, interprets the complex data and provides a diagnosis.


“Our current tests can be expensive, time consuming and aren’t always accurate,” said Patel (pictured at right). “Next Generation Sequencing will revolutionize the microbiology field. With the information it provides we can fine-tune patient treatment.”

This technology also removes the need for lengthy guesswork. For example, if an Ontario patient has a fever and a severe headache during the summer, doctors would normally test for West Nile virus. But those test results are frequently negative. Instead of speculating, doctors can now let high-powered computers discover what’s in the sample.

“Dr. Patel’s work in pathogen discovery aims to deliver a one-stop-shop that can definitely determine the causative organisms in severe infections such as meningitis and encephalitis,” said Vanessa Allen, chief of medical microbiology at Public Health Ontario. “This has the potential to revolutionize the way we deliver microbiology diagnostics for improved patient care.”


Patel, a clinical microbiologist, began using this technology for the Pathogen Discovery Program at Public Health Ontario in 2012. The goal of the program is to diagnose difficult cases and to quickly and accurately identify bacteria and viruses that could cause an outbreak.

During an outbreak, Patel could also track where the bugs come from and how they are evolving.  Others have used Next Generation Sequencing to identify and track specific strains of Ebola in West Africa.

“Should any outbreak occur in Ontario, we could test samples, identify the bacteria or virus that is causing the outbreak and track the spread using a systematic process,” said Patel. “We can also see how infectious a virus or bacteria is, and if similar strains are circulating through other parts of the world.”

Patel predicts that the technology will be ready for clinicians to use for routine testing in about a year.

“The program will help diagnose patients who have inconclusive routine test results, and will also enhance the public health response to an outbreak in Ontario. A lot of times we’re in a reactive mode, but this is an area where we’re getting ahead of the game.”


By Katie Babcock [en línea] Toronto (CAN):, 21 de mayo de 2015 [ref. 22 de abril de 2015] Disponible en Internet:

How blood group O protects against malaria

18 05 2015

It has long been known that people with blood type O are protected from dying of severe malaria. In a study published in Nature Medicine, a team of Scandinavian scientists explains the mechanisms behind the protection that blood type O provides, and suggest that the selective pressure imposed by malaria may contribute to the variable global distribution of ABO blood groups in the human population.

Anopheles albimanus mosquito. Credit: James Gathany (Wikimedia Commons).

Malaria is a serious disease that is estimated by the WHO to infect 200 million people a year, 600,000 of whom, primarily children under five, fatally. Malaria, which is most endemic in sub-Saharan Africa, is caused by different kinds of parasites from the plasmodium family, and effectively all cases of severe or fatal malaria come from the species known as Plasmodium falciparum. In severe cases of the disease, the infected red blood cells adhere excessively in the microvasculature and block the blood flow, causing oxygen deficiency and tissue damage that can lead to coma, brain damage and, eventually death. Scientists have therefore been keen to learn more about how this species of parasite makes the infected red blood cells so sticky.

It has long been known that people with blood type O are protected against severe malaria, while those with other types, such as A, often fall into a coma and die. Unpacking the mechanisms behind this has been one of the main goals of malaria research.

A team of scientists led from Karolinska Institutet in Sweden have now identified a new and important piece of the puzzle by describing the key part played by the RIFIN protein. Using data from different kinds of experiment on cell cultures and animals, they show how the Plasmodium falciparum parasite secretes RIFIN, and how the protein makes its way to the surface of the blood cell, where it acts like glue. The team also demonstrates how it bonds strongly with the surface of type A blood cells, but only weakly to type O.


Conceptually simple

Principal investigator Mats Wahlgren, a Professor at Karolinska Institutet’s Department of Microbiology, Tumour and Cell Biology, describes the finding as “conceptually simple”. However, since RIFIN is found in many different variants, it has taken the research team a lot of time to isolate exactly which variant is responsible for this mechanism.

“Our study ties together previous findings”, said Professor Wahlgren. “We can explain the mechanism behind the protection that blood group O provides against severe malaria, which can, in turn, explain why the blood type is so common in the areas where malaria is common. In Nigeria, for instance, more than half of the population belongs to blood group O, which protects against malaria.”

The study was financed by grants from the Swedish Foundation for Strategic Research, the EU, the Swedish Research Council, the Torsten and Ragnar Söderberg Foundation, the Royal Swedish Academy of Sciences, and Karolinska Institutet. Except Karolinska Institutet, co-authors of the study are affiliated to Stockholm University, Lund University, Karolinska University Hospital, and the national research facility SciLifeLab in Sweden, and to the University of Copenhagen in Denmark and University of Helsinki in Finland. Mats Wahlgren is a shareholder and board member of drug company Dilaforette AB, which is working on an anti-malaria drug. The company was founded with support from Karolinska Development AB, which helps innovators with patent-protected discoveries reach the commercial market.



RIFINs are Adhesins Implicated in Severe Plasmodium falciparum Malaria

Suchi Goel, Mia Palmkvist, Kirsten Moll, Nicolas Joannin, Patricia Lara, Reetesh Akhouri, Nasim Moradi, Karin Öjemalm, Mattias Westman, Davide Angeletti, Hanna Kjellin, Janne Lehtiö, Ola Blixt, Lars Ideström, Carl G Gahmberg, Jill R Storry, Annika K. Hult, Martin L. Olsson, Gunnar von Heijne, IngMarie Nilsson and Mats Wahlgren

Nature Medicine, AOP 9 March 2015, doi: 10.1038/nm.3812
 [en línea] Solna (SUE):, 18 de mayo de 2015 [ref. 10 de marzo de 2015] Disponible en Internet:

Individual’s unique microbial ‘fingerprint’ drastically affects home environment

6 10 2014

A person’s home is their castle, and they populate it with their own subjects: millions and millions of bacteria.


A recent study investigated the complex interplay between the teeming communities of microbes that are unique to each person and the bacteria found in their homes. Courtesy of Argonne National Laboratory

A study published last week in Science provides a detailed analysis of the microbes that live in houses and apartments. The study was conducted by researchers from the U.S. Department of Energy’s Argonne National Laboratory and the University of Chicago.


The results shed light on the complicated interaction between humans and the microbes that live on and around us. Mounting evidence suggests that these microscopic, teeming communities play a role in human health and disease treatment and transmission.


“We know that certain bacteria can make it easier for mice to put on weight, for example, and that others influence brain development in young mice,” said Argonne microbiologist Jack Gilbert, who led the study. “We want to know where these bacteria come from, and as people spend more and more time indoors, we wanted to map out the microbes that live in our homes and the likelihood that they will settle on us.


“They are essential for us to understand our health in the 21st century,” he said.


The Home Microbiome Project followed seven families, which included eighteen people, three dogs and one cat, over the course of six weeks. The participants in the study swabbed their hands, feet and noses daily to collect a sample of the microbial populations living in and on them. They also sampled surfaces in the house, including doorknobs, light switches, floors and countertops.


Then the samples came to Argonne, where researchers performed DNA analyses to characterize the different species of microbes in each sample.


“We wanted to know how much people affected the microbial community on a house’s surfaces and on each other,” Gilbert said.


They found that people substantially affected the microbial communities in a house—when three of the families moved, it took less than a day for the new house to look just like the old one, microbially speaking.


Regular physical contact between individuals also mattered—in one home where two of the three occupants were in a relationship with one another, the couple shared many more microbes. Married couples and their young children also shared most of their microbial community.


Within a household, hands were the most likely to have similar microbes, while noses showed more individual variation.


Adding pets changed the makeup as well, Gilbert said—they found more plant and soil bacteria in houses with indoor-outdoor dogs or cats.


In at least one case, the researchers tracked a potentially pathogenic strain of bacteria called Enterobacter, which first appeared on one person’s hands, then the kitchen counter and then another person’s hands.


“This doesn’t mean that the countertop was definitely the mode of transmission between the two humans, but it’s certainly a smoking gun,” Gilbert said.


“It’s also quite possible that we are routinely exposed to harmful bacteria—living on us and in our environment—but it only causes disease when our immune systems are otherwise disrupted.”


Home microbiome studies also could potentially serve as a forensic tool, Gilbert said. Given an unidentified sample from a floor in this study, he said, “we could easily predict which family it came from.”


The research also suggests that when a person (and their microbes) leaves a house, the microbial community shifts noticeably in a matter of days.

“You could theoretically predict whether a person has lived in this location, and how recently, with very good accuracy,” he said.


Researchers used Argonne’s Magellan cloud computing system to analyze the data; additional support came from the University of Chicago Research Computing Center.


The study was funded by the Alfred P. Sloan Foundation. Additional funding also came from the National Institutes of Health, the Environmental Protection Agency and the National Science Foundation.


Other Argonne researchers on the study included Argonne computational biologist Peter Larsen, postdoctoral researchers Daniel Smith, Kim Handley and Nicole Scott, and contractors Sarah Owens and Jarrad Hampton-Marcell. UChicago graduate students Sean Gibbons and Simon Lax contributed to the paper, as well as collaborators from Washington University in St. Louis and the University of Colorado at Boulder.
 [en línea] Chicago, IL (USA):, 06 de octubre de 2014 [ref. 02 de septiembre de 2014] Disponible en Internet:

Una plataforma biocomputacional analizará células cancerosas y bacterias

14 04 2014

Útil para poder predecir el comportamiento que seguirán las células cancerosas y las bacterias ante un tratamiento específico

Científicos de la Universidad de Costa Rica (UCR) crearán una plataforma biocomputacional que procese rápidamente toda la información de las investigaciones que tratan de combatir la resistencia de las células cancerosas a la quimioterapia y de las bacterias a los antibióticos.


El investigador principal del proyecto es el Dr. Francisco Siles Canales, coordinador del Laboratorio de Investigación en Reconocimiento de Patrones y Sistemas Inteligentes. FOTO: UCR.

El investigador principal del proyecto es el Dr. Francisco Siles Canales, coordinador del Laboratorio de Investigación en Reconocimiento de Patrones y Sistemas Inteligentes. FOTO: UCR.


En el combate de las células cancerígenas y de las bacterias los científicos se topan con el problema de que estos agentes infecciosos son resistentes a las terapias que se aplican para eliminarlos y curar el mal.
En el caso de las células cancerígenas, poseen mecanismos autodefensivos que hacen que algunas sobrevivan a la quimioterapia aunque queden dañadas en su Ácido Desoxirribonucleico (ADN).

Las bacterias se vuelven más resistentes a los antibióticos que van enfrentando, por lo que constantemente hay que estar creando nuevos y más poderosos.

Para poder predecir el comportamiento que seguirán las células cancerosas y las bacterias ante un tratamiento específico, es necesario procesar una cantidad inmensa de información, para lo cual se requiere una poderosa capacidad de procesamiento computacional.

Contar con este recurso es lo que se propone el equipo interdisciplinario de científicos agrupados en la Red de Investigación en Biocomputación (RIB), disciplina que aplica métodos computacionales, matemáticos e ingenieriles a problemas biológicos.

El investigador principal del proyecto es el Dr. Francisco Siles Canales, coordinador del Laboratorio de Investigación en Reconocimiento de Patrones y Sistemas Inteligentes (PRIS-Lab) de la Escuela de Ingeniería Eléctrica de la Universidad de Costa Rica (UCR).

También participan investigadores de la Facultad de Microbiología y del Centro de Investigación en Enfermedades Tropicales (CIET) de la UCR. Asimismo investigadores de la Escuela de Salud Pública y del Centro de Investigaciones en Tecnologías de la Información y Comunicación (CITIC).


Matemáticas, células y bacterias

El Dr. Siles explicó que este equipo multidisciplinario está avocado a “construir un modelo matemático que describa el proceso defensivo a los tratamientos por parte de estos agentes que causan enfermedades, para luego implementarlo en la computadora”.

“Es decir que no se quede como un modelo teórico, sino que ese modelo teórico se implemente y que podamos validarlo experimentalmente con los colegas de microbiología. Nosotros proponemos el modelo analítico, lo simulamos en la computadora, lo llevamos al laboratorio y vemos que tan cierto es y lo que vaya saliendo mal lo vamos ajustando.”

Para comprobar la efectividad de las predicciones del modelo matemático se debe trabajar inicialmente con líneas de bacterias y de células cancerosas que estén ampliamente estudiadas y de las cuales se tenga mucha información.

Sobre las células, uno de los miembros del equipo multidisciplinario, el microbiólogo Steve Quirós Barrantes, dijo que van “a trabajar con líneas cancerosas que están sumamente estudiadas, de las cuales se conocen muy bien los detalles y están muy bien descritas, porque llevan ya muchos años de análisis por parte de la comunidad científica.”

Explicó que esa numerosa información se utilizará para desarrollar la plataforma y comprobar si el modelo matemático logra predecir acertadamente el comportamiento de determinado cultivo de células cancerosas al aplicársele alguna quimioterapia específica.

Si se comprueba en el laboratorio que la evolución de las celular es igual al que predijo la plataforma biocomputacional, entonces se podrá aplicar para prever el comportamiento de otras células o bacterias en estudio.

El proyecto se denomina “Plataforma biocomputacional de análisis de datos genómicos para superar la resistencia a la terapia contra el cáncer y las infecciones microbianas”. A finales del 2013 ganó recursos del Fondo de Incentivos que concede anualmente el Ministerio de Ciencia, Tecnología y telecomunicaciones (MICITT).

El Dr. Siles coordina también la Red de Investigación en Computación Científica, creada también por investigadores de la UCR en colaboración con el Colaboratorio Nacional de Computación Avanzada (CNCA), del Centro Nacional de Alta Tecnología (CeNAT), así como también otros centros y laboratorios de investigación costarricenses y extranjeros. [en línea] Salamanca (ESP):, 14 de abril de 2014 [ref. 11 de abril de 2014] Disponible en Internet:

Secrets of trail-blazing bacteria revealed

22 07 2013

Bacteria in slimy biofilms are able to spread rapidly over surfaces such as catheters by building a transport network with DNA for tracks, say Australian researchers.

Microbiologist Associate Professor Cynthia Whitchurch from the University of Technology, Sydney and colleagues report their findings today in the journal Proceedings of the National Academy of Sciences.

Extracellular DNA (yellow) organises traffic flow of individual bacteria (blue) as a biofilm expands and spreads infection (Source: E. Gloag and L. Turnbull/The ithree institute and University of Technology Sydney)

Extracellular DNA (yellow) organises traffic flow of individual bacteria (blue) as a biofilm expands and spreads infection (Source: E. Gloag and L. Turnbull/The ithree institute and University of Technology Sydney)

“By following each other along this network and behaving the rules they can move quite efficiently through the system and out to the front of the biofilm,” says Whitchurch.

“We believe this is the equivalent to how a bacterial biofilm would expand up a catheter.”

Bacteria colonise the surfaces of our body, and the environment, in communities held together with slime.

These “biofilms” are a real problem because they make the bacteria resistant to antibiotics and disinfectants, and to the immune systems of organisms.

“They’re really resistant to everything we can throw at them, pretty much,” says Whitchurch.

“Probably half of hospital-acquired infections are due to biofilms forming on implanted medical devices … like catheters.”

If a biofilm establishes on a catheter, it can migrate and spread infection up to the bladder and kidneys, says Whitchurch.

To investigate how biofilms form and expand into new areas she and colleagues studied Pseudomonas aeruginosa, a bacteria that commonly causes urinary tract and respiratory infections.


Virtual tracking

The researchers used a technique called high-resolution phase-contrast time-lapse microscopy to track the movement of thousands of individual bacterial cells on computer.

“For the first time we could get quantitative data of individual cell movements during the process of biofilm expansion,” says Whitchurch. 

She and colleagues were able to show the cells lining up in co-ordinated fashion to blaze new trails.

Atomic force microscopy revealed that the advancing bacteria were forging furrows, which constituted the edges of the network.

Fluorescence microscopy revealed that DNA excreted by the bacteria provided the network “tracks” that organised the flow of bacterial traffic.

“You have long ropes of DNA that the bacteria are aligning themselves to,” says Whitchurch.

To demonstrate the role of the DNA the researchers used an enzyme to chew up the DNA.

“When we remove the DNA, the bacteria completely lose their ability to co-ordinate their behaviours. They start bouncing around as individual cells and end up in traffic jams and the whole rate of expansion of the biofilm seizes up.”


Bulldozing bacteria

Importantly, Whitchurch and colleagues also found that the DNA was also helping to glue together individual bacteria, called “bulldozer aggregates”, which collectively forged new furrows ahead of them. 

“They can’t move out into new territory individually. They have to act as a collective to do that,” says Whitchurch.

She says if this is indeed how bacterial biofilms colonise, it suggests ways of controlling biofilms on medical devices such as catheters.

“One opportunity is to build our own networks that tell the bacteria to go in a way that doesn’t enable their biofilm to expand,” says Whitchurch.

Whitchurch suggests it might be possible to insert small furrows on the devices using microfabrication that would limit the spread of the biofilm.

“We could build our own furrows and get the bacteria running around in futile circles instead of co-ordinating themselves to move along the device,” she says. [en línea] Sydney (AUS):, 22 de julio de 2013 [ref. 25 de junio de 2013] Disponible en Internet:

Bacteria targets pancreatic cancer in mice

29 04 2013


An experimental therapy that uses Listeria bacteria to infect pancreatic cancer cells and deliver tumour-killing drugs has shown promise in mice, say US scientists.


Radioactive bacterium: Ninety per cent of mice treated with radioactive listeria showed no evidence of cancer spread after three weeks(Source: Centers for Disease Control and Prevention)

Radioactive bacterium: Ninety per cent of mice treated with radioactive listeria showed no evidence of cancer spread after three weeks(Source: Centers for Disease Control and Prevention)

While it remains unknown whether the method might work in people, the researchers say they are encouraged by its ability to halt cancer’s spread.

“At this point, we can say that we have a therapy that is very effective for reducing metastasis in mice,” says co-author Dr Claudia Gravekamp, associate professor of microbiology and immunology at Albert Einstein College of Medicine of Yeshiva University in New York.

The experimental technique described in the Proceedings of the National Academies of Science works by using a weakened form of Listeria, a bacterium which in its wild form can cause foodborne illness.

Pancreatic cancer tends to spread quickly through the body and is particularly lethal, since it is often discovered only once it has progressed beyond the pancreas.

Untreated patients usually die within three to six months, and the five-year survival rate is just four per cent.

In previous research, Gravekamp’s team discovered that Listeria could be used to infect tumour cells with antigens. While the bacterium was cleared from normal cells by the body’s immune system within three to five days, it accumulated in the immunosuppressed tumours.

“Based on these results we hypothesized that Listeria could be used to deliver anticancer agents such as radionuclides,” they write.

In this experiment, the researchers attached a radioactive isotope to the bacteria and injected it into mice with pancreatic cancer. They found the radioactive bacteria infected cancer cells but not normal cells.

Ninety per cent of mice with pancreatic cancer treated with the technique showed no evidence of cancer spread after three weeks.

Researchers halted the experiment at 21 days because that is when the control mice, who had pancreatic cancer, but were not treated, began to die.

The treatment stopped the cancer’s spread in most cases, and appeared to have no ill effects on the mice, but more work needs to be done to see if it may extend survival time.

“With further improvements, our approach has the potential to start a new era in the treatment of metastatic pancreatic cancer,” says Gravekamp. [en línea] Sydney (AUS):, 29 de abril de 2013 [ref. 23 de abril de 2013] Disponible en Internet:

More than a Machine

20 12 2012

Ribosome regulates viral protein synthesis, revealing potential therapeutic target 


Some viruses depend on ribosomal protein L40 (rpL40), highlighted within the large (60S) subunit, for protein synthesis. Image courtesy of the Whelan Lab.

Some viruses depend on ribosomal protein L40 (rpL40), highlighted within the large (60S) subunit, for protein synthesis. Image courtesy of the Whelan Lab.

By ELIZABETH COONEY Viruses can be elusive quarry. RNA viruses are particularly adept at defeating antiviral drugs because they are so inaccurate in making copies of themselves. With at least one error in every genome they copy, viral genomes are moving targets for antiviral drugs, creating resistant mutants as they multiply. In the best-known example of success against retroviruses, it takes multiple-drug cocktails to corner HIV and narrow its escape route.

Rather than target RNA viruses themselves, aiming at the host cells they invade could hold promise, but any such strategy would have to be harmless to the host.  Now, a surprising discovery made in ribosomes may point the way to fighting fatal viral infections such as rabies.

Results were published online November 19 in Proceedings of the National Academy of Sciences.

The ribosome has traditionally been viewed as the cell’s molecular machine, automatically chugging along, synthesizing proteins the cell needs to carry out the functions of life. But Amy Lee, a former graduate student in the program of virology, and Sean Whelan, HMS professor of microbiology and immunobiology, now say the ribosome appears to take a more active role, regulating the translation of specific proteins and ultimately how some viruses replicate.

The researchers were studying differences between how viruses and the host cells they infect carry out the process of translating messenger RNAs (mRNAs) into proteins. Focusing on protein components found on the surface of the ribosome, they discovered a protein that some viruses depend on to make other proteins, but that the vast majority of cellular mRNAs do not need.

Called rpL40, this ribosomal protein could represent a target for potential treatments; blocking it would disable certain viruses while leaving normal cells largely unaffected.

“Because certain viruses are very sensitive to the presence and absence of these ribosomal proteins, it might be a useful way for us to think about targeting ribosomes for therapeutic purposes from an antiviral standpoint,” said Whelan. “This is a way to think about interfering with rabies virus infection. There are no therapeutics for rabies infection.”

The team screened protein constituents of the ribosome to see which ones might be involved in specialized protein synthesis. Studying the vesicular stomatitis virus, a rhabdovirus in the same family as the rabies virus, they found that its mRNAs depended on rpL40 but only 7 percent of host-cellular mRNAs did. Some of the cellular mRNAs that depend upon rpL40 were stress response genes.

Experiments in yeast and human cells revealed that a class of viruses, which includes rabies and measles, depended on rpL40 for replication.

“This work reveals that the ribosome is not just an automatic molecular machine but instead also acts as a translational regulator,” said first author Amy Lee, who is now a post-doctoral researcher at the University of California, Berkeley.

The concept of targeting cellular functions such as protein synthesis for antiviral therapies is being explored by a number of research groups, but there are no drugs based on this.

“We think the principle is bigger than just this single protein,” Whelan said.  “Viruses have an uncanny way of teaching us new biology all the time.”

Maria Barna, assistant professor of developmental biology and genetics at Stanford University, called the work part of an exciting area of exploration. Her own recently published findings showed that a single ribosomal protein belonging to the large ribosome subunit rpL38 is critically required for formation of the mammalian body plan and specialized translational control.
“It is extremely fascinating that one single ribosomal protein is required for translational control of so many viruses, while its loss does not appear to have a major consequence on general protein synthesis or for cell viability. Any means to down-regulate rpL40 may be a novel therapeutic approach for viral infections,” she said about work led by Whelan. Barna was not involved in the research. “However, a deeper understanding is critically needed to determine whether the few ribosomal proteins, such as rpL40, shown to exert ribosome-mediated translational specificity reflects a harbinger of a new layer of gene regulation.”

This work was supported by NIH grants AI059371 and AI057159. Whelan is a recipient of a Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Award. Lee is supported by the Department of Defense through the National Defense Science & Engineering Graduate Fellowship Program and the National Science Foundation through the Graduate Research Fellowship Program. [en línea] Cambridge, MA (USA):, 20 de diciembre de 2012 [ref. 26 de noviembre de 2012] Disponible en Internet: