Wednesday, 27 June 2018

Carbon metabolism of intracellular bacterial pathogens and possible links to virulence


New technologies such as high-throughput methods and 13C-isotopologue-profiling analysis are beginning to provide us with insight into the in vivo metabolism of microorganisms, especially in the host cell compartments that are colonized by intracellular bacterial pathogens. In this Review, we discuss the recent progress made in determining the major carbon sources and metabolic pathways used by model intracellular bacterial pathogens that replicate either in the cytosol or in vacuoles of infected host cells.
  • Recent progress has expanded our knowledge about the metabolism of the model bacterial pathogens Listeria monocytogenesShigella flexneri (and the closely related enteroinvasive Escherichia coli (EIEC)), Salmonella enterica subsp. enterica serovar Typhimurium and Mycobacterium tuberculosiswhen living inside the host cell.
  • Differences in the metabolic characteristics of these four pathogens have been elucidated in the context of the metabolism of host cell lines used for in vitro infection.
  • There are several tools available to study the metabolism of these intracellular pathogens, and differential gene expression profiling (DGEP) and 13C isotopologue analysis (13C-IPA) have been particularly fruitful; however, there are both strengths and weaknesses for these techniques.
  • Models have been suggested (mainly on the basis of data from DGEP and 13C-IPA studies) for the metabolic pathways and fluxes used by the four pathogens when replicating in their specific intracellular compartments (the cytosol or specific phagosomal vacuoles of the host cell). Each pathogen adapts specifically to the host cell environment but exhibits a surprisingly high metabolic flexibility in response to altered metabolic conditions.
  • There is limited experimental evidence for interference by the metabolism of these intracellular bacteria with the expression of virulence genes that are required for their intracellular lifestyles.
  • There is an urgent need for improved in vivo systems and more sensitive analytical tools for studying the metabolism of the bacterial pathogens in real target cells and animal models. source:
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Monday, 25 June 2018

Sensitive and fast identification of bacteria in blood samples by immunoaffinity mass spectrometry for quick BSI diagnosis

Bloodstream infections rank among the most serious causes of morbidity and mortality in hospitalized patients, partly due to the long period (up to one week) required for clinical diagnosis. In this work, we have developed a sensitive method to quickly and accurately identify bacteria in human blood samples by combining optimized matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and efficient immunoaffinity enrichment/separation. A library of bacteria reference mass spectra at different cell numbers was firstly built. Due to a reduced sample spot size, the reference spectra could be obtained from as few as 10 to 102 intact bacterial cells. Bacteria in human blood samples were then extracted using antibodies-modified magnetic beads for MS fingerprinting. By comparing the sample spectra with the reference spectra based on a cosine correlation, bacteria with concentrations as low as 500 cells per mL in blood serum and 8000 cells per mL in whole blood were identified. The proposed method was further applied to positive clinical blood cultures (BCs) provided by a local hospital, where Escherichia coli and Staphylococcus aureus were identified. Because of the method’s high sensitivity, the BC time required for diagnosis can be greatly reduced. As a proof of concept, whole blood spiked with a low initial concentration (102 or 103 cells per mL) of bacteria was cultured in commercial BC bottles and analysed by the developed method after different BC times. Bacteria were successfully identified after 4 hours of BC. Therefore, an entire diagnostic process could be accurately accomplished within half a day using the newly developed method, which could facilitate the timely determination of appropriate anti-bacterial therapy and decrease the risk of mortality from bloodstream infections. Source:

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Friday, 22 June 2018

“Kill Switch” Prevents Spread of Genetically Modified Bacteria

As genetically-modified microbes take on ever more tasks – from creating new pharmaceuticals to turning out clean fuel sources – researchers have searched for a way to biologically isolate them from their wild counterparts, so that if they were ever accidentally released, they wouldn’t be able to survive.
Now, scientists releasing two separate papers in the journal Nature think they have a solution. They unveiled two different approaches to modifying a strain of E. coli to make it dependent on artificial nutrients. In a controlled environment, such as a research lab or factory, scientists would provide that sustenance. But if the bacteria break free, they wouldn’t be able to make the compounds themselves, and would die.

No Escape

Scientists have previously used similar approaches, making GMO bacteria reliant on synthetic nutrients. But in the past, the GMO bacteria have evolved the ability to live without the synthetic nutrients. Bacteria have ejected the part of their DNA that made them reliant on the nutrients, or they figured out how to cobble together an equivalent of those nutrients from the natural world.
In separate projects, teams led by Yale molecular biologist Farren Isaacs and Harvard molecular geneticist George Church have genetically modified E. coliso that it is totally dependent on synthetic amino acids. And in both cases that need is built in to multiple parts of the bacteria’s genome – 49 times in the Harvard study – so that the likelihood that the bacteria would evolve to overcome the restriction is unlikely. And both strains showed an undetectably small escape rate – the number of E. coli able to survive without being fed the synthetic amino acid.

Out in the Open

Church and Isaacs said that their work is most likely to be used in pharmaceutical or dairy operations – making cheese, yogurt or drugs. These processes happen in closed facilities and fermenters. Unlike in the fields, bees or breezes won’t spread genetically modified material around, but there is a risk of contamination if the microscopic bacteria get onto employees’ clothing or into the air.
Meanwhile the scientists hope their research lays the groundwork for larger applications of modified bacteria in open-air settings, including for bioremediation – the use of living organisms to clean up polluted sites like landfills and oil spills. In these settings a reliance on synthetic amino acids mean the genetically modified organisms could be “contained” molecularly even if they are no longer physically contained.

Future Uses

The safety features aren’t the only appealing attribute of the modified E. colifeatured in the new papers. The scientists also built in resistance to a number of viruses. That means the bacteria are safe from attack by viruses that can be devastating in food or pharmaceutical manufacturing – like when viral contamination caused a Genzyme Corp. plant to halt manufacturing in 2009, temporarily cutting off the medication supply for some patients.
Church noted that the viral resistance could be an incentive to “sweeten the offer” and encourage companies to use “safe” GMOs. The technique could also provide intellectual property protection for industrial, pharmaceutical or food companies, since they could make their own GMOs dependent on specific synthetic amino acids, and other companies would have trouble replicating those modified organisms without the “key.” Such built-in IP protection could actually encourage collaboration between different companies, Isaacs said.
“This is really motivated by anticipating the impact biotechnology will have over the next several decades, recognizing the importance of endowing these GMOs with more sophisticated functions, to have more safety measures going forward,” Isaacs told reporters. “Endowing safeguards will be important to allow the field to progress.”

Thursday, 21 June 2018

Infectious Diseases

Infectious diseases are caused by living organisms, they pose two problems to medicine and public health. First, pathogens can grow and replicate, allowing them to evolve drug resistance or change just enough to be unrecognized by our memory immune cells. Second, they are contagious and potentially lead to outbreaks. Human-to-human transmission is outlined in more detail in the figure below. There is even human-to-animal transmission.
Modes of Infectious Disease Transmission (A) Pathogens can be transferred by environmental factors, such as wind and water. They can also be transferred between humans, as well as from humans to animal vectors. Animal vectors can further spread the disease through migration (if carried by birds or fish) or trade. (B) Human-to-human transmission has been classified into five main modes . These five modes are not mutually exclusive; for example, the Ebola virus can be spread through direct contact and, potentially, through droplet transmission. How pathogens can be transmitted mostly depends on how “hardy” they are outside a human body. Some cannot survive for long periods of time, so they require direct contact, droplet transmission, or transmission through an animal vector. Others, such as flu, can survive for long periods of time on surfaces – making them extremely contagious. Fecal-oral pathogens are a large problem in developing countries, but not in developed countries such as the US.
In order to control outbreaks, we often call upon epidemiologists. Epidemiologists observe how health-related events are distributed in the population and use that information to determine their causes and control their spread. In fact, John Snow (described in the first paragraph) is celebrated as one of the fathers of epidemiology. Drawing from John Snow’s example, we can see that the solution to fighting epidemics requires coordination between multiple agencies, including citizens, scientists, physicians, and government officials. In the US, this job often falls to the CDC, and internationally, the World Health Organization (WHO).
In conclusion, infectious diseases are caused by microorganisms that can hijack the nutrients and cellular machinery in our bodies. Fortunately, our immune system and current therapies can keep us healthy. In fact, according to the WHO,  infectious, maternal, neonatal, and nutritional-related diseases combined caused about 23% of deaths around the world . However, the recent Ebola outbreak has shown us that infectious diseases are still a major threat. This is especially important with an increasing amount of global travel and a lack of new drugs . We can do our part by taking sick leave or avoiding travel when ill, taking antimicrobial drugs properly (finishing the course), getting the appropriate vaccinations to protect those vulnerable in the population (through herd immunity), and asking scientists and politicians to make infectious diseases a priority. source:

Wednesday, 20 June 2018


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Monday, 18 June 2018

History of Antibiotics

Antibiotics have been used for millennia to treat infections, although until the last century or so people did not know the infections were caused by bacteria. Various moulds and plant extracts were used to treat infections by some of the earliest civilisations – the ancient Egyptians, for example, applied mouldy bread to infected wounds. Nevertheless, until the 20th century, infections that we now consider straightforward to treat – such as pneumonia and diarrhoea – that are caused by bacteria, were the number one cause of human death in the developed world.

It wasn’t until the late 19th century that scientists began to observe antibacterial chemicals in action. Paul Ehrlich, a German physician, noted that certain chemical dyes coloured some bacterial cells but not others. He concluded that, according to this principle, it must be possible to create substances that can kill certain bacteria selectively without harming other cells. In 1909, he discovered that a chemical called arsphenamine was an effective treatment for syphilis. This became the first modern antibiotic, although Ehrlich himself referred to his discovery as 'chemotherapy' – the use of a chemical to treat a disease. The word 'antibiotics' was first used over 30 years later by the Ukrainian-American inventor and microbiologist Selman Waksman, who in his lifetime discovered over 20 antibiotics.

Alexander Fleming was, it seems, a bit disorderly in his work and accidentally discovered penicillin. Upon returning from a holiday in Suffolk in 1928, he noticed that a fungus, Penicillium notatum, had contaminated a culture plate of Staphylococcus bacteria he had accidentally left uncovered. The fungus had created bacteria-free zones wherever it grew on the plate. Fleming isolated and grew the mould in pure culture. He found that P. notatum proved extremely effective even at very low concentrations, preventing Staphylococcus growth even when diluted 800 times, and was less toxic than the disinfectants used at the time.

After early trials in treating human wounds, collaborations with British pharmaceutical companies ensured that the mass production of penicillin (the antibiotic chemical produced by P. notatum) was possible. Following a fire in Boston, Massachusetts, USA, in which nearly 500 people died, many survivors received skin grafts which are liable to infection by Staphylococcus. Treatment with penicillin was hugely successful, and the US government began supporting the mass production of the drug. By D-Day in 1944, penicillin was being widely used to treat troops for infections both in the field and in hospitals throughout Europe. By the end of World War II, penicillin was nicknamed 'the wonder drug' and had saved many lives.

Scientists in Oxford were instrumental in developing the mass production process, and Howard Florey and Ernst Chain shared the 1945 Nobel Prize in Medicine with Alexander Fleming for their role in creating the first mass-produced antibiotic. source:

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Wednesday, 13 June 2018

Attacking bacteria with shark skin-inspired surfaces

Sharks are often the subject of TV specials or news stories focusing on their attacks on humans. But scientists are finding that sharks could inspire a new type of surface that would attack bacteria, helping humans instead of hurting them. As reported in ACS Applied Materials & Interfaces, researchers have designed a coating that is infused with antimicrobial agents and has the patterned diamond-like texture of shark skin.

Fighting bacteria is an ongoing battle, resulting in more than 2 million infections and 23,000 deaths in the U.S. every year, according to the U.S. Centers for Disease Control and Prevention. As a result of overusing antibiotics, bacterial resistance to these drugs is on the rise. Patients in hospitals who are already battling illnesses or have compromised immune systems are especially at risk of developing infections just by touching contaminated bedrails and door knobs. Scientists have been developing coatings for these high-touch surfaces to fight the spread and growth of microbes. For example, Sharklet AF™ is a coating designed to mimic a shark's skin, and it reduces the ability of bacteria to adhere to surfaces. But long-term use will result in bacteria accumulation. James J. Watkins, Jessica D. Schiffman and colleagues wanted to see if adding titanium dioxide (TiO2) nanoparticles, which are antibacterial, to a shark skin material would efficiently fight off microbes.

The team printed their own shark skin surfaces with polymer and ceramic composites, and added titanium dioxide nanoparticles to them. The shark skin surface without nanoparticles reduced the attachment of E. coli by 70 percent compared to smooth films. But shark skin surfaces with TiO2 nanoparticles exposed to UV light for one hour killed off over 95 percent of E. coli and 80 percent of Staphylococcus aureus. The group says the fabrication method could be scaled up for mass production.

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Sunday, 10 June 2018

Infectious Diseases

Infectious diseases are disorders caused by organisms — such as bacteria, viruses, fungi or parasites. Many organisms live in and on our bodies. They're normally harmless or even helpful, but under certain conditions, some organisms may cause disease.
Some infectious diseases can be passed from person to person. Some are transmitted by bites from insects or animals. And others are acquired by ingesting contaminated food or water or being exposed to organisms in the environment.
Signs and symptoms vary depending on the organism causing the infection, but often include fever and fatigue. Mild infections may respond to rest and home remedies, while some life-threatening infections may require hospitalization.
Many infectious diseases, such as measles and chickenpox, can be prevented by vaccines. Frequent and thorough hand-washing also helps protect you from most infectious diseases.


Each infectious disease has its own specific signs and symptoms. General signs and symptoms common to a number of infectious diseases include:
  • Fever
  • Diarrhea
  • Fatigue
  • Muscle aches
  • Coughing

When to see a doctor

Seek medical attention if you:
  • Have been bitten by an animal
  • Are having trouble breathing
  • Have been coughing for more than a week
  • Have severe headache with fever
  • Experience a rash or swelling
  • Have unexplained or prolonged fever
  • Have sudden vision problems


Infectious diseases can be caused by:
  • Bacteria. These one-cell organisms are responsible for illnesses such as strep throat, urinary tract infections and tuberculosis.
  • Viruses. Even smaller than bacteria, viruses cause a multitude of diseases — ranging from the common cold to AIDS.
  • Fungi. Many skin diseases, such as ringworm and athlete's foot, are caused by fungi. Other types of fungi can infect your lungs or nervous system.
  • Parasites. Malaria is caused by a tiny parasite that is transmitted by a mosquito bite. Other parasites may be transmitted to humans from animal feces.

Direct contact

An easy way to catch most infectious diseases is by coming in contact with a person or animal who has the infection. Three ways infectious diseases can be spread through direct contact are:
  • Person to person. A common way for infectious diseases to spread is through the direct transfer of bacteria, viruses or other germs from one person to another. This can occur when an individual with the bacterium or virus touches, kisses, or coughs or sneezes on someone who isn't infected.
    These germs can also spread through the exchange of body fluids from sexual contact. The person who passes the germ may have no symptoms of the disease, but may simply be a carrier.
  • Animal to person. Being bitten or scratched by an infected animal — even a pet — can make you sick and, in extreme circumstances, can be fatal. Handling animal waste can be hazardous, too. For example, you can acquire a toxoplasmosis infection by scooping your cat's litter box.
  • Mother to unborn child. A pregnant woman may pass germs that cause infectious diseases to her unborn baby. Some germs can pass through the placenta. Germs in the vagina can be transmitted to the baby during birth.

Indirect contact

Disease-causing organisms also can be passed by indirect contact. Many germs can linger on an inanimate object, such as a tabletop, doorknob or faucet handle.
When you touch a doorknob handled by someone ill with the flu or a cold, for example, you can pick up the germs he or she left behind. If you then touch your eyes, mouth or nose before washing your hands, you may become infected.

Insect bites

Some germs rely on insect carriers — such as mosquitoes, fleas, lice or ticks — to move from host to host. These carriers are known as vectors. Mosquitoes can carry the malaria parasite or West Nile virus, and deer ticks may carry the bacterium that causes Lyme disease.

Food contamination

Another way disease-causing germs can infect you is through contaminated food and water. This mechanism of transmission allows germs to be spread to many people through a single source. E. coli, for example, is a bacterium present in or on certain foods — such as undercooked hamburger or unpasteurized fruit juice.

Risk factors

While anyone can catch infectious diseases, you may be more likely to get sick if your immune system isn't working properly. This may occur if:
  • You're taking steroids or other medications that suppress your immune system, such as anti-rejection drugs for a transplanted organ
  • You have HIV or AIDS
  • You have certain types of cancer or other disorders that affect your immune system
In addition, certain other medical conditions may predispose you to infection, including implanted medical devices, malnutrition and extremes of age, among others.


Most infectious diseases have only minor complications. But some infections — such as pneumonia, AIDS and meningitis — can become life-threatening. A few types of infections have been linked to a long-term increased risk of cancer:
  • Human papillomavirus is linked to cervical cancer
  • Helicobacter pylori is linked to stomach cancer and peptic ulcers
  • Hepatitis B and C have been linked to liver cancer
In addition, some infectious diseases may become silent, only to appear again in the future — sometimes even decades later. For example, someone who's had a chickenpox infection may develop shingles much later in life.


Infectious agents can enter your body through:
  • Skin contact or injuries
  • Inhalation of airborne germs
  • Ingestion of contaminated food or water
  • Tick or mosquito bites
  • Sexual contact
Follow these tips to decrease your risk of infecting yourself or others:
  • Wash your hands. This is especially important before and after preparing food, before eating, and after using the toilet. And try not to touch your eyes, nose or mouth with your hands, as that's a common way germs enter the body.
  • Get vaccinated. Immunization can drastically reduce your chances of contracting many diseases. Make sure to keep up to date on your recommended vaccinations, as well as your children's.
  • Stay home when ill. Don't go to work if you are vomiting, have diarrhea or have a fever. Don't send your child to school if he or she has these signs and symptoms, either.
  • Prepare food safely. Keep counters and other kitchen surfaces clean when preparing meals. Cook foods to the proper temperature using a food thermometer to check for doneness. For ground meats, that means at least 160 F (71 C); for poultry, 165 F (74 C); and for most other meat, at least 145 F (63 C).
    In addition, promptly refrigerate leftovers — don't let cooked foods remain at room temperature for extended periods of time.
  • Practice safe sex. Always use condoms if you or your partner has a history of sexually transmitted infections or high-risk behavior.
  • Don't share personal items. Use your own toothbrush, comb and razor. Avoid sharing drinking glasses or dining utensils.
  • Travel wisely. If you're traveling out of the country, talk to your doctor about any special vaccinations — such as yellow fever, cholera, hepatitis A or B, or typhoid fever — you may need.

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