We Need More Science: 07/24/14

Linking microbial, immune environment in semen to HIV viral load, transmission

While HIV is found in many body fluids, sexual transmission through semen is the most common route of infection. Consequently, the amount of virus in semen (the semen viral load) affects the likelihood of HIV transmission. Besides sperm, semen also contains immune factors and communities of bacteria, an environment that could influence the viral load. Research published on July 24th in PLOS Pathogens reports that HIV infection re-shapes the relationship between semen bacteria and immune factors which in turn affects viral load, suggesting that the semen microbiome plays a role in sexual transmission of HIV.

Researchers led by Lance Price, from the Translational Genomics Research Institute, USA, and Rupert Kaul, from the University of Toronto, Canada, studied the relationship of semen bacteria with HIV infection by analyzing semen samples from 49 men who have sex with men (MSM). They focused on MSM because of the high risk of sexual HIV transmission in this population. 27 of the men were HIV infected, and provided samples both before they started anti-retroviral therapy (ART) and one and six months after. Samples from 22 MSM not infected with HIV served as controls.

In HIV-infected men not on ART, overall numbers of bacteria in the samples -- the semen bacterial load -- was correlated with HIV viral load. Analyzing the bacterial DNA in the samples, the researchers detected a total of 248 unique types of bacteria in semen from the controls, on average 71 different ones per sample. In samples from HIV-infected untreated men, semen microbiome diversity was markedly reduced, and the relative abundance of the more common bacterial groups differed. ART for six months reduced semen viral load to undetectable levels, and restored bacterial diversity and composition to a situation similar to the controls.

There was no correlation in uninfected controls between levels of immune factors and semen bacterial load. In contrast, in HIV-infected men, several factors, and most strongly one called interleukin-1beta (IL-1b), a mediator of inflammation, showed a correlation with both semen bacterial load and semen viral load.

"While delineating the directionality and causality of the complex relationships they observed will require further studies," the researchers say, their data "suggest an interaction between semen microbiome, local immunology, and semen viral load. Higher bacterial load in semen could lead to higher IL-1b levels, which in turn could induce viral shedding, thereby increasing viral load." They conclude that the results "support the hypothesis that semen bacteria play a role in local inflammation and HIV shedding, and that they are a possible target for reducing HIV transmission."

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The above story is based on materials provided by PLOS . Note: Materials may be edited for content and length.

Detecting Salmonella in pork meat processing: New methods

Infections caused by foodborne microorganisms are an increasing public health burden. In a PhD project at the National Food Institute, Technical University of Denmark, new methods of characterising and dectecting foodborne illness-causing Salmonella in pork meat processing and in bacteria in water, feed and food samples were studied.

Traditional methods of characterizing and detecting bacteria are often slow and time-consuming. Therefore, development of new methods of characterising and detecting illness-causing microorganisms is very important for improving food safety.

Trine Hansen, PhD student at the National Food Institute, has studied new methods of characterising Salmonella in pork meat processing and detecting unknown bacteria in water, feed and food samples.

The research project has given a better understanding of which factors in pork meat processing may contribute to the development of more appropriate processing environments, which can limit the occurrence of Salmonella.

Furthermore, a method based on concentration and sequencing of parts of the genome for all microorganisms present in e.g. a water sample was also tested, enabling researchers to find not only the microorganisms they are specifically looking for. This method was tested on B. cereus in water samples and can be used for discovering bacterial contamination in e.g. foodborne outbreaks where the contamination source is unknown.

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The above story is based on materials provided by Technical University of Denmark (DTU) . Note: Materials may be edited for content and length.

One route to malaria drug resistance found

Researchers have uncovered a way the malaria parasite becomes resistant to an investigational drug. The discovery, at Washington University School of Medicine in St. Louis, also is relevant for other infectious diseases including bacterial infections and tuberculosis.

The study appears July 24 in Nature Communications.

Many organisms, including the parasite that causes malaria, make a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy, whether plants, animals or bacteria. In malaria, the investigational drug fosmidomycin blocks isoprenoid synthesis, killing the parasite. But over time the drug often becomes less effective.

"In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study," said senior author Audrey R. Odom, MD, PhD, assistant professor of pediatrics. "We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?"

Fosmidomycin, an antibiotic, is being evaluated against malaria in phase 3 clinical trials in combination with other antimalarial drugs.

Using next-generation sequencing technology, the research team compared the genetics of malaria parasites that responded to the drug to the genetics of malaria parasites that were resistant to it. With this approach, Odom and her colleagues found mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

"The PfHAD1 protein is completely unstudied," Odom said. "It's a member of a larger family of proteins, and there are almost no biological functions assigned to them."

In malaria parasites, Odom's team showed that the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing. Since isoprenoids are necessary for life, it's not clear why the organism would purposefully slow down isoprenoid production.

"We don't know why the protein puts the brakes on under normal conditions," Odom said. "Perhaps simply because it's an energetically expensive pathway. But loss of PfHAD1 releases the brakes, increasing the pathway's activity, so that even when the drug is there, it doesn't kill the cells."

Odom says isoprenoid synthesis is an attractive drug target not just for malaria but for tuberculosis and other bacterial infections because these organisms also rely on this same isoprenoid pathway. While people make isoprenoids, these vital compounds are manufactured entirely differently in animals compared with many infectious pathogens likely to cause disease.

Inhibiting isoprenoid manufacturing in malaria, bacteria or tuberculosis, for example, would in theory leave the human pathways safely alone. In people, perhaps the most well-known isoprenoid is cholesterol, with statin drugs famously inhibiting that manufacturing pathway.

Odom, who treats patients at St. Louis Children's Hospital, said she sees a handful of malaria cases each year, mostly in patients who have recently traveled to parts of the world where malaria is common. The parasite remains a massive global health problem, causing about 627,000 deaths in 2012 alone, according to the World Health Organization. Most deaths are in children under age 5.

Despite this public health burden, malaria is understudied in the lab because it is notoriously difficult to grow. It has a complex lifecycle that includes two-way transfers between mosquito and human and spans different forms in the human liver and red blood cells.

"The malaria parasite is difficult to work with in the lab; it's nearly impossible to replicate the lifecycle," Odom said. "That's why it was so exciting to be able to do this kind of study in malaria, rather than in a typical model organism like yeast. This genetic study would not have been possible even five years ago because the gene sequencing technology was not there."

Sapronoses: Diseases of another kind, caused by pathogenic microorganisms

The drought that has the entire country in its grip is affecting more than the color of people's lawns. It may also be responsible for the proliferation of a heat-loving amoeba commonly found in warm freshwater bodies, such as lakes, rivers and hot springs, which the drought has made warmer than usual this year.

A 9-year-old Kansas girl recently died of an infection caused by this parasite after swimming in several area lakes. The amoeba enters the body through the nose of an individual and travels to the brain. Nose plugs can lower the odds of this rare but fatal pathogen entering the body.

The amoeba, Naegleria fowleri , is classified as a sapronosis, an infectious disease caused by pathogenic microorganisms that inhabit aquatic ecosystems and/or soil rather than a living host. Scientists at UC Santa Barbara studying infectious disease transmission published their findings in the latest issue of the journal Trends in Parasitology.

"Sapronoses do not follow the rules of infectious diseases that are transmitted from host to host," said lead author Armand Kuris, a professor in UCSB's Department of Ecology, Evolution and Marine Biology (EEMB). "They are categorically distinct from the way we think infectious diseases should operate. The paper tries to bring this group of diseases into sharp focus and get people to think more clearly about them."

A well-known example of a sapronosis is Legionnaires' disease, caused by the bacteria Legionella pneumophila , which can be transmitted by aerosolized water and/or contaminated soil. The bacteria can even live in windshield-wiper fluid. Legionnaires' disease acquired its name in July 1976, when an outbreak of pneumonia occurred among people attending an American Legion convention at the Bellevue-Stratford Hotel in Philadelphia. Of the 182 reported cases, mostly men, 29 died.

A major group of emerging diseases, sapronotic pathogens can exist independently in an environmental reservoir like the cooling tower of the Philadelphia hotel's air conditioning system. Some rely on mosquitoes to find disease hosts for them. Zoonoses, by contrast, require a human host.

According to Kuris, diseases borne by a vector -- a person, animal or microorganism that carries and transmits an infectious pathogen into another living organism -- are more or less virulent depending on how efficiently they are transmitted. As a result, virulence evolves to a level where it is balanced with transmission in order to maximize the spread of the virus. However, Kuris noted that there is no virulence trade-off for sapronotic disease agents. Transmission of a sapronosis pathogen is able to persist regardless of any changes in host abundance or transmission rates.

To quantify the differences between sapronoses and conventional infectious diseases, the researchers developed a mathematical model using population growth rates. Of the 150 randomly selected human pathogens examined in this research, one-third turned out to be sapronotic -- specifically 28.6 percent of the bacteria, 96.8 percent of the fungi and 12.5 percent of the protozoa.

"The fact that almost all of the fungi we looked at are sapronotic is a noteworthy generalization," Kuris said.

"You can't model a sapronosis like valley fever with classic models for infectious diseases," said co-author Kevin Lafferty, adjunct faculty in EEMB and a marine ecologist with the Western Ecological Research Center of the U.S. Geological Survey. "To combat sapronoses, we need new theories and approaches. Our paper is a start in that direction."

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The above story is based on materials provided by University of California - Santa Barbara . The original article was written by Julie Cohen. Note: Materials may be edited for content and length.

Human parasite Leishmania is a probiotic for the fly that carries it

The Leishmania parasite, which causes the human disease leishmaniasis, acts as a probiotic in the insect that transmits it to humans, protecting them from bacterial disease.

Research by Lancaster University published in the open access journal Parasites and Vectors suggest that using bacterial controls to stop the spread of leishmaniasis could sometimes have the opposite effect to that intended, by benefiting flies carrying the parasite.

Dr Rod Dillon said: "We're looking at using bacteria to stop the spread of Leishmaniasis, but it turns out that the Leishmania parasite works as a kind of probiotic and reduces the mortality of the fly."

Around 12 million people are currently infected with leishmaniasis worldwide, mostly in South America, Africa and Asia. It is estimated to kill 20-50,000 people per year. Sandflies transmit the parasite by feeding on an infected mammal and, if they survive long enough, feeding on another mammal, and passing the parasite on to them.

Dr Fernando Genta said: "Finding out that sandflies can benefit from Leishmania infection was a surprise. It changes the way we think about the vector-parasite interaction. From an evolutionary point of view, it may be interesting for sandflies to have a part of its population permissive to Leishmania infection. This may be one explanation for the maintenance of this interaction throughout time.

"Our finding states an alert for vector control strategies. If you try to use a pathogen to reduce sandflies population, you may favor the Leishmania infected insects. In the end, it may increase the chance of human infections."

The team from Lancaster University were studying sandflies' interactions with bacteria, to find a new way to control the sandfly populations, and curb the spread of leishmaniasis. They set out to study the effects on the sandfly of carrying both the Leishmania parasite and the bacterial pathogen Serratia marcescens, a naturally occurring disease in sandfly populations.

The team took a population of Lutzomyia longipalpis sandflies and fed them blood meal containing the Leishmania parasite, and a second group with uninfected blood meal. They then fed both groups with the Serratia pathogen. The group that were carrying the Leishmania parasite had a survival rate of 56% after six days, in contrast to the control group, which had a survival rate of just 11%. This showed that carrying both the Leishmania parasite and the bacterial pathogen protected the flies and increased their lifespan.

The authors say that this finding is important for efforts to develop biological controls against vectors of disease using bacterial pathogens, as these may have unexpected effects in the wild.

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The above story is based on materials provided by Lancaster University . Note: Materials may be edited for content and length.

Mapping the Mass of an Enormous Galaxy Cluster

Mass map of galaxy cluster MCS J0416.1–2403 using strong and w

ESA/Hubble, NASA, HST Frontier Fields Acknowledgement: Mathilde Jauzac (Durham University, UK and Astrophysics & Cosmology Research Unit, South Africa) and Jean-Paul Kneib (École Polytechnique Fédérale de Lausanne, Switzerland)

You are looking at the most precise gravity map ever made of a distant galaxy cluster. Using the map, astronomers have determined that the cluster is roughly 650,000 light-years across and contains enough matter to make 160 trillion suns.

The cluster, known as MCS J0416.1–2403, is located about 4 billion light-years away and consists of hundreds of galaxies all orbiting one another. Newton’s gravitational equations can tell you the mass of two objects orbiting one another, provided you already know the mass of one of them. However, because these galaxies are all so distant, there is no way for scientists to determine any of their individual masses.

But there is another way. Einstein’s theory of general relativity tells us that heavy objects warp the fabric of space-time around them. As light travels through these warped regions it will become distorted, and we see that as smeared out rings and arcs in our telescopes, an effect known as gravitational lensing (you can see these streaks in the visible light image below). Using the Hubble space telescope, astronomers identified smudges in the light seen around MCS J0416.1–2403. These distortions are images of even more distant galaxies sitting behind the cluster; their light has been lensed by its enormous mass. By carefully determining just how much the light is smeared out, researchers can calculate the amount of matter sitting within the galaxy cluster.

The 160 trillion solar masses includes both visible matter and dark matter, which gives off no light but makes up the bulk of the cluster’s mass. By studying the dynamics of all the galaxies within the cluster, astronomers can better understand this mysterious substance. Researchers will also continue mapping the smeared out images to increase the precision of their mass calculations, learning about the cluster’s finer details to figure out its history and evolution.