Author Archives: ycpmicro
Hello, and welcome to all new/returning YCP students! Additionally, welcome to all new BIO230 students–I hope everyone has had a restful and relaxing summer break. I know I sure did; I had fun during summer Micro, had a week long break, and accomplished some important Science in my spare time. One thing I did not do was update this forum. Looking back, it appears I last opened up WordPress back sometime in April. Let’s see if we can do something about that!
I found a news alert on ASM’s Microbe World site, which gives an update on the Zombie Ant story. It summarized work out of the entomology department at Penn State University, which has been studying a fascinating example of symbiosis between an insect and a fungus called Ophiocordyceps. What is most interesting about this relationship is that infection by the fungus causes behavioral changes in the host. These changes are advantageous for the fungus–the ant moves over a greater range, allowing the spores of the fungus to spread further. Obviously, infection of a colony would be a Bad Thing, leading to this observation on the phenomenon of “Social Immunity”.
Social Immunity has been observed in laboratory settings in a variety of insect species. It prevents the spread of diseases within colonies, however it has not been previously observed in field conditions. In a study published recently in PLOS One, researchers placed ants which had been freshly killed by the fungus inside one of two nests; one nest had live ants, and the second nest had no ants. The fungus-killed ants were rapidly removed from the living nest, and no further fungal infection occurred of that colony. This result suggests that effective reproduction of the fungus requires being outside of the colony.
In an expanded study, researchers examined the dynamics between the appearance of infected dead ants outside of colonies (sources of infection) and the position of foraging trails (future hosts) in several colonies over the course of 20 months. The researchers observed a consistent appearance of 14.5 cadaver ants per month per colony. Based on this low rate of infection and the lack of colony collapse, the researchers proposed that this fungal parasite represents a “chronic” infection of these colonies. The authors suggest that the removal of corpses from the colony or ants dying in isolation outside the colony may be an essential step in the development of Ophiocordyceps to a stage that enables the fungus to infect a new host.
Despite my dire announcements regarding the potential challenges in treating infectious diseases in the near future, which are coming about due to a combination of biological and economic reasons, there are some reasons to be somewhat optimistic. Via Microbe, the monthly newsletter from the American Society of Microbiology, an article which summarizes some of the research into novel antibiotics that are currently in clinical trials. The article lists at least 39 potential antibacterial compounds under investigation at present, with 25 of those under what is termed Phase 2 or Phase 3. In Phase 2 or Phase 3 trials, the compounds have shown promise in in vitro or animal models, have been found to be safe to administer to humans, and therefore are being assessed to see if they show therapeutic promise in humans. Leading the search for new antimicrobials are small biotech companies such as Cubist here in the US, and the large company Hoffman-La Roche from Switzerland.
One of the very interesting targets is an enzyme called DNA topoisomerase, which catalyzes the unwinding of DNA during the process of DNA replication. Many of these compounds are from the quinolone class of antimicrobials, some of which are easily taken up into host cells, thereby allowing them to be effective against intracellular pathogens such as Legionella pneumophilia and Mycoplasma pneumoniae. The target of these compounds are enzymes that are found in all cells, including human cells, however they are able to demonstrate the principle of selective toxicity by inhibiting the prokaryotic enzymes as opposed to eukaryotic enzymes. Some studies have described side effects where the DNA replication of mitochondria can be inhibited as well.
Other important antimicrobial compounds under investigation inhibit protein synthesis, and a number of compounds are currently under intense review for effectiveness. Some of these compounds have been identified by manipulating known antimicrobials (semi-synthetic compounds) or are the result of new compounds identified by screening environmental microorganisms for inhibitory compounds.
One of the major problems due to antibiotic use in appropriate situations is the rise in other infections, which arise as the normal microbial flora are reduced by the use of the antibiotic. Clostridium difficile infections are increasing in frequency at present, and are themselves beginning to demonstrate antibiotic resistance. Several new compounds under investigation appear to target C. difficile infections very specifically, enabling them to be much more effective against the pathogen in question, while having little effect on other microbes. This approach will help to forestall the emergence of other antibiotic resistance microorganisms, at least for a while.
Via the ever helpful Morbidity Mortality Weekly Report, another alert about the dangers of foodborne-illness! The Minnesota Department of Health reported in late July 2013 two cases of invasive listeriosis, for which molecular analysis indicated a sole-source for infection. As an aside, the Minnesota Department of Health seems to be the hardest working state department of health, as evidenced by this alert about Salmonella from Guinea pigs, and this alert about Salmonella from phlebotomy that I found in the BIO230 archives. Way to go, Minnesota Department of Health!
Once the Centers for Disease Control and Prevention were notified, further analysis indicated that the isolate was also identical to an environmental isolate collected from a cheese producer in 2011. With this in place, several other cases were also identified by the CDC in last summer’s outbreak, resulting in one death and one miscarriage. All patients were interviewed to determine their “cheese exposure.” All patients indicated that they had likely eaten one or more of Crave Brothers Farmstead Cheese varieties (Les Frères, Petit Frère, or Petit Frère with truffles) during the likely time frame for infection, at either grocery stores or restaurants in the region. All of the cheeses were shipped as intact wheels to the point of sale, where they were cut and repackaged.
The manufacturer issued a voluntary recall when news of the outbreak was made public. Conjecture by the CDC suggested that the contamination arose during the manufacturing process. The process of pasteurization very effectively eliminates Listeria monocytogenes from milk, however in the cheesemaking process contamination can occur after the original pasteurization. The CDC recommends that strict sanitation and monitoring of contamination steps always be in place for cheesemakers, regardless of whether pasteurized milk is used.
The CDC also reiterated standard precautions to protect against infection by Listeria, which again bear repeating. The organism does not generally pose a significant health risk to the general population, however immunocompromised individuals can become quite seriously ill. Additionally, pregnant women can pass the organism onto the developing baby, and fetal infection due to Listeria is a significant cause of miscarriage. Because of these risks, at risk individuals are strongly advised to avoid any food that carries the potential for infection by Listeria.
I apologize for the slow pace of updates this semester; it has been hectic, and scouring the news for alerts of general microbiological interest to post here has taken a backseat to grading for the past few weeks. However, I came across a review article from the latest issue of Trends In Microbiology that is timely with regards to our current class discussion about antibiotics and their place in modern medicine.
I have painted a less than rosy picture many times in this forum about the future of medicine, primarily as a result of the diminishing utility of antibiotics. The premise is this: the more antibiotics are used to treat infectious disease, the less they are ultimately effective as a result of the acquisition of antibiotic resistance. Indeed, the observation that genes conferring antibiotic resistance to today’s antibiotics have been found in thousands of years old samples of bacteria in permafrost suggests that acquisition of resistance is not a matter of “if it happens,” but rather “when it happens” to antibiotics that haven’t even been developed yet.
In our viewing of the Frontline episode “Hunting the Nightmare Bacteria” in class the other day, one of the most alarming points come out to me was the highlighting of the problem of who is supposed to deal with with looming catastrophe. The majority of the large pharmaceutical companies have pulled out of the antibiotic business due to a simple financial decision–it costs a tremendous amount of money to bring new drugs to market, and by their nature antibiotics give a very poor return on investment. At the same time, it was also clear that there is no national consensus to determine the scope of the problem or what the most appropriate response should be.
The review article takes the following stance; public health officials must be proactive in recognizing the severity of the issue, and governments need to take the lead in prioritizing antibiotic discovery in both academic and industrial settings. Public-Private partnerships (PPPs) have been established in small scale between not-for-profit charities, small biotech companies, and large pharmaceutical firms, however the lack of financial return has limited their effectiveness to date. The model however is valid, and if adopted large scale the financial burden of bringing these critical drugs to market can be distributed broadly between the academic, governmental, and industrial players. Such a model in the current political climate in the United States is difficult, but not impossible to propose. These organizations have successfully come into being in Europe which has traditionally had a more open interaction between government and industry, however the passing in the US of the Prescription Drug User Fee Act (PDUFA V) provides financial incentives for novel antibiotic development in this country. Hopefully, these incentives will allow medicine to stay ahead of antibiotic resistance at least for a little while!
One of the major issues that health care will be facing is the decreasing effectiveness of antibiotics against infectious disease. The ability of microorganisms to become resistant to many different antibiotics is expensive, and leads to increased mortality to many infections that have previously been easily treatable. Sherrell Carter (11 AM Micro) found an article from the medical journal Chemistry and Biology that reports an “outside the box” type of idea; some common anti-inflammatory drugs used to treat aches and pains also have effects on microorganisms, and this might be exploited to treat infections due to those organisms. Here is Sherrell’s summary:
Amazing how certain commonly over the counter drugs that aid daily Americans in their struggles against aches, pains, fever, and inflammation are also believed to have the ability to eradicate bacteria and prevent infection. Innovative research at the University of Wollongong, in Australia suggest that these drugs, better known as nonsteroidal anti-inflammatory drugs, act on bacteria in a way that is incorrigibly different from current antibiotics. This discovery could provide new developments for fighting drug-resistant infections and ‘superbugs that pose a threat on human health.
Scientist has discovered that some anti-inflammatory drugs used in human and veterinary medicine have weak antibiotic activity and that they prevent bacteria from copying their DNA, needed for replication. Dr. Aaron Oakley of the University of Wollongong, in Australia analyzed three NSAIDs: bromofenac, carprofen, and vedaprofen. I’m flabbergasted to know that a class of meds that can be found in our medicine cabinet are among pharmaceutical residences like aspirin, ibuprofen, and naproxen, impairing the proper functioning of bacteria’s DNA.
I was bewildered by Dr. Oakley and his team ability to recognize that anti-inflammatory drugs can bind to and inhibit a specific protein in bacteria called the DNA clamp. Our common everyday over counter drugs have an amazing benefit to our immune system. It was noted in the study that DNA clamp, is an enzyme that synthesizes DNA molecules from their nucleotide building blocks across various bacterial species.
Subsequently, it’s amazing to feel excitingly ahead the race of bacterial infections and retired overused antibiotics. But as we race to our local pharmacy for over the counter assistance’s we may need to exercise a little patience’s before we can claim an instant cure. Nevertheless, carprofen, vedaprofen and bromfenac require additional testing before it can be prescribed precisely as an antibiotic.