Category Archives: Microbiology

Cancer Treatment Saves the Life of an HIV Patient – For the Second Time

I’m finally finding time to finish a blog post on the announcement Nature made earlier in March with a pretty big headline subject: for only the second time ever, an individual infected with HIV is “cured” – as much as it is humanly possible to be cured of HIV – via stem cell transplant.

University of Cambridge’s (UK) Ravindra Gupta, MD, led the study of this patient, whose name has not be released (I’ll use the term “2019 patient”). Researchers like Gupta actually warn against using the term “cured” to describe this person’s health status. So why are people (the media) saying that the 2019 patient is cured? Because the 2019 patient stopped taking antiretroviral drugs 18 months ago (16 months after receiving the stem cell transplant), and HIV has not returned.

Plus, the headline “person is cured of HIV” sounds a lot better than “person’s HIV’s levels have not returned after receiving stem cell transplant and halting antiretroviral treatment.” I won’t go on a tear about the issues with sensationalism in science journalism (right now, anyway).

The 2019 patient joins the ranks of Timothy Ray Brown, the ‘Berlin Patient,” who was “cured” in 2018 and still appears HIV free.

Berlin vs. London

Both Brown and the 2019 patient had a form of blood cancer that did not respond to chemotherapy, which prompted doctors to conduct a bone marrow transplant to replace diseased blood cells with healthy stem cells. These stem cells just so happened to also produce a very rare form of HIV-resistance. So these two patients came out of their procedure on their way to being both cancer-free and HIV-free.

In the case of the 2019 patient, doctors purposely chose a bone marrow donor who carried the HIV resistance trait – two copies of a mutation in a gene called CCR5. Experts estimate that just one percent of people of European descent carry the two-copy genetic mutation providing HIV resistance.

The CCR5 gene codes for a white blood cell receptor involved in the immune response to viral invaders like HIV. HIV binds the CCR5 receptor to attack white blood cells. So when CCR5 is not working normally due to a genetic mutation, HIV cannot attack white blood cells in the same way.

Before Brown received his stem cell transplant a decade ago, doctors tried aggressive chemotherapy and radiotherapy to treat his cancer. For the 2019 patient, doctors chose a less aggressive approach consisting of chemotherapy and drugs. Experts from the study acknowledge the difference in treatments as a sign that stem cell transplantation as a treatment for HIV infection does not require aggressive treatments to be effective.

Why only two?

So why not make stem cell transplant a standard procedure to treat HIV infection? The procedure is risky, more so than just continuing to suppress HIV with a daily drug regimen. The transplant could fail, or it could result in a lethal autoimmune attack. Other potential consequences include organ damage, respiratory distress, fluid overload, infection, and low platelets and red blood cells. Plus, HIV infection makes everything more dangerous.

Although stem cell transplants won’t quite work as a catch-all treatment for anyone infected with HIV, the basic concept behind the success of both patients “cured” of HIV yields promise. In laboratories all over the world, scientists are likely hard at work developing gene therapies targeting CCR5.

HIV/AIDS Basics

HIV (human immunodeficiency virus) is the virus – the “microbial agent” – that causes AIDS (acquired immunodeficiency syndrome) – the “disease – just like rhinovirus (“microbial agent”) causes the common cold (“disease”). HIV is a particularly devastating virus because it attacks the very cells employed by the human body to defend itself: CD4 immune cells.

Antiretroviral therapy (ART) does not lead to a cure, but it does improve quality of life and reduce the risk of an HIV-positive person passing the infection to someone else. ART accomplishes both tasks by preventing HIV from multiplying – minimizing the amount of virus in an infected person’s blood and preventing a person with an HIV infection from becoming a person with AIDS.

“It takes two to make a thing go right; It takes two to make it outta sight”
A commentary by Science Kara

Now that two people have been “cured” of HIV via the same means, I can’t image that it will be too long before researchers are publishing new studies on CCR5 gene therapy, conducting studies in vitro, in mice, and in chimpanzees. It will be a while until there are studies done with humans (per usual in science), but I don’t think it will be another 11 years before there is another major breakthrough in treatments for HIV more conclusive than ART.

In the midst of all the news reporting on the 2019 patient earlier this month, my favorite piece was from The Daily podcast and host Michael Barbaro from the New York Times. Barbaro goes beyond the science of the matter that I’ve discussed here and talks about the history of the HIV epidemic to truly represent how significant it is to declare the second “cure” of an individual infected with HIV.

References

Matthew Warren’s “Second patient free of HIV after stem-cell therapy.” published online as news for the journal Nature on March 5, 2019.

The National Institutes of Health website “AIDSinfo.”

Johns Hopkins Medicine

FDA Alert On Cilantro From Puebla, Mexico

The recent report of a cyclosporiasis outbreak from cilantro plants is not the first to be issued. Outbreaks also occurred in 2012, 2013, and 2014, all pointing to cilantro from the Mexican state of Puebla.

Cyclospora cayetanensis is a protozoan pathogen that specifically infects humans (cyclosporiasis). Protozoan infections are generally more difficult to treat than bacterial or viral infections since protozoa are eukaryotes, just like us. Fewer anti-protozoa treatments exist since there are more similarities between humans and protozoa (and thus less unique targets for drugs) than there are between humans and bacteria (bacteria are prokaryotes – because there are so many differences between human cells and bacteria cells we have a lot of targets for antibacterials).

Cyclosporiasis infections cause diarrhea (like other food-poisoning-related illnesses). In addition to being infected directly from eating contaminated cilantro, people can also become ill through contamination from feces of someone already infected.

Since 2013, the FDA has investigated “11 farms and packing houses that produce cilantro in the state of Puebla” and found 8 farms to either be carrying C. cayetanensis or to be exhibiting dangerous conditions capable of harboring the parasite. The FDA report said these suspect farms contained “human feces and toilet paper found in growing fields and around facilities.”

Because of these findings, the FDA concluded that cilantro products from Puebla are “subject to refusal of admission,” meaning companies receiving cilantro from Puebla can refuse shipments without examination. It is important to note that this FDA report does not include “multi-ingredient processed foods” containing cilantro (only fresh cilantro, intact or cut/chopped).

For the next couple of months if you are buying fresh cilantro, make sure to check the origin of its cultivation. Until the FDA lifts the alert on cilantro from Puebla, it’s not safe to eat. However if you do develop food-poisoning symptoms after eating cilantro, you will be okay. Refuel your body with electrolytes and water – and maintain strict hygiene! You want to flush the parasite out of your system without infecting anyone else.

 

#ScienceKara #GoGuacamole

For more on this issue, check out the following resources:

LabRoots Coverage

Direct access to FDA report

How should you dry your hands?

One of my passions surrounding “biological awareness” so-to-speak is proper hand-washing behavior (see my BuzzFeed article – http://tinyurl.com/BacterialResistance). The perspective I want to take today, however, is actually the practice of drying hands after washing them. What is the best way to dry your hands post-cleansing? *My perspective of “best” = most sanitary*

Let’s look at some common options:

  1. Hand dryer
  2. Paper towels
  3. Cloth towel

Let’s go ahead and knock out that last option. Cloth towels are infamous for quickly becoming cesspools of germs like Coliform bacteria and Escherichia coli (1). E. coli is an infamous pathogen known for playing a role in cases of food-poisoning. Coliform bacteria are a group of bacteria commonly transferred by fecal contamination. These bacteria alone are not highly pathogenic, but their presence indicates a high incidence of other more dangerous germs that are similarly transmitted.

Poor hand-washing techniques exacerbate the colonization of these microorganisms. When microorganisms colonize, they are growing into communities of germs that are derived from a common ancestor and are increasingly resilient as they grow into larger numbers.  If one person does not adequately scrub their hands with soap and remove all dangerous infectious agents while washing, these leftover germs are transferred to the cloth towel. Also, since hand towels will realistically remain moist during the majority of their existence, essentially the perfect environment is created for many bacteria to grow and thrive until the next person comes along to dry their hands. Little does this person know, all progress made moments ago at the sink are erased (and potentially made worse) by re-infecting your hands with the germs harbored by the towel.

Our next option: utilizing hot air and friction (by rubbing your hands together) under an automatic hand dryer. This may seem like the best option because often you do not have to press a button or touch anything else after cleaning your hands. The preferred hand dryer is motion-activated and effectively dries your hands in 45 seconds. UNC Chapel Hill pharmacy student and science enthusiast Tim Angle is convinced that the warm air from these dryers is generated from a place swarming with bacteria. “Air dryers distribute bacteria due to their moist, warm environment that is prime for growing bacteria,” Angle explains. However, back in 2000, scientists showed that the air emitted from hand dryers is in fact just as sanitary as paper towels (2). In addition, in 2012, a group of researchers found that the air leaving a hand dryer actually had fewer microorganisms than the air entering it (3).

Nevertheless, Angle is still correct about the capability of warm air hand dryers to spread bacteria. This seemingly flawless method of using air to dry just-washed hands is still, in some ways, faulty. According to an article by three scientists comparing the hand-drying efficacy of various methods, warm air dryers and jet air dryers are more likely than drying hands with paper towels to spread potentially infectious droplets to the environment (4).

Dr. Christy Esmahan, a molecular biologist, brings up another flaw of warm air hand dryers. “It takes so long that people tend to leave with their hands still moist — a magnet for fresh germs.” Just like a wet cloth towel provides a fruitful breeding ground for germs, still-wet hands provide the same environment, especially when people leaving a restroom are highly likely to touch door handles and cell phones within seconds.

Considering my strictly sanitation focus, paper towels could very well be the best method for hand drying. One-time use greatly decreases risk of contamination in comparison to cloth towels. In addition, using paper towels includes the same benefit of frictional removal of bacteria as rubbing hands under a warm air dryer, while eliminating the high incidence of spreading potentially contaminated droplets to the environment.

hand drying preferences chart
Image 1: A Random Survey of Hand-Drying Preferences

Indeed, in a study of 47 random participants, a large majority preferred paper towels to warm air hand dryers (Image 1). However, the evidence for the sanitation of paper towels may not be enough to convince the large number of environmentally-concerned citizens to abandon warm air hand dryers and cloth towels. 63% of people preferring hand-drying methods other than paper towels mentioned reduction of waste as the main motivation for their choice. In addition, although the large majority of the surveyed participants did choose paper towels as their hand-drying method of choice, only 25% of those participants mentioned cleanliness and sanitation as their reasoning. 25% rationalized their choice with speed and efficiency.

Therefore, the concluding question seems to be not only “Which method is the most sanitary?” but also “How should the most appropriate method be communicated?” and, thinking holistically, “Should we be more concerned about sanitation or waste reduction?” Those who are biologically biased will likely continue to clash with the environmentally-minded. However, potential future projects that could bring the two fields together could revolve around biodegradable paper towels, for example. Ultimately, the question you should be asking yourself after reading this article is this:

What will it take to change YOUR daily hand-drying habits?

References

  1. Gerba, Charles P., Tamimi, Akrum H., Maxwell, Sherri, Sifuentes, Laura Y., Hoffman, Douglas R., Koenig, David W. 2014. Bacterial Occurrence in Kitchen Hand Towels. Food Protection Trends. 34(5): 312-317.
  2. Best, E.L., Parnell, P, Wilcox, M.H. December 2014. Microbiological comparison of hand-drying methods: the potential for contamination of the environment, user, and bystander. Journal of Hospital Infection. 88(4): 199-206.
  3. Huang, C., Ma, Wenjun, Stack, Susan. 2012. The Hygienic Efficacy of Different Hand-Drying Methods: A Review of the Evidence. Mayo Clinic Proceedings. 87(8): 791-798.
  4. Tayler, J.H., Brown, K.L., Toivenen, J, Holah J.T. December 2000. A microbiological evaluation of warm air hand driers with respect to hand hygiene and the washroom environment. Journal of Applied Microbiology. 89(6): 910-919.

Important Links

https://www.ChristyEsmahan.com

Agrobacterium: A Biological Syringe

Plants, just like humans, fall victim to bacterial infections. Dr. Ann Matthysse, a researcher in the Department of Biology at the University of North Carolina, has studied interactions between plants and pathogens since 1970, when she thought that Agrobacterium tumefaciens might lead to advances with cases of human cancer.

Matthysse initially thought that A. tumefaciens, a Gram-negative, rod-shaped bacterium found in upper layers of the soil, could be a model for cancer because it causes tumors in plants (Figure 1)

She found instead that the cancer-causing mechanism utilized by A. tumefaciens has virtually nothing to do with human cancer. However, continuing studies with the bacterium is still very beneficial due to its unique initial surface reactions with wounded plants as it binds them to begin infection.

Matthysse describes A. tumefaciens as “a biological syringe” because its virulence comes from a transfer of DNA upon infection of a plant wound, a process unique to this specific plant bacteria2. The transferred DNA integrates into the host cell chromosome and transforms the plant’s cells into tumor cells. These transformed cells then make metabolites that only A. tumefaciens is able to utilize as an energy source. The virus essentially taps into the host plant’s energy source in the same way a cell phone charger would pull energy from your car battery. This results in smaller fruit than normal being produced by the plant host, but it is usually not fatal to the plant unless the tumor blocks its main vascular tissue. Additionally, these initial surface interactions involved in DNA transfer will function the same even if non-natural, specifically-selected genes are inserted into the bacterium for transfer into a plant.

Now, Matthysse is interested in manipulating this mechanism to more efficiently develop genetically engineered crops. Some crops have been difficult to engineer, but these problems can be alleviated by identifying restrictions on the host range for agrobacterium. “Because if we knew what [these factors] were,” she proclaims, “it might be possible to counteract them.”2 If A. tumefaciens can be manipulated to bind to these plants like it does to other plant hosts, one could engineer some of these crops. For example, one could transfer genes that resist pathogenic fungi, and there is opportunity to improve nutrient levels in certain foods. “For example, rice that contains a lot of vitamin A, which would be good for people in India that don’t have a lot of vitamin A in their diet, has been made by putting the genes for vitamin A biosynthesis into rice.”

In 2006, the Centers for Disease Control and Prevention (CDC) reported that an Escherichia coli outbreak occurred from the bacteria infecting salad vegetables and causing disease in those eating the vegetables raw (Figure 2). In the numerous studies that were based on the results reported, Salmonella was also identified as a cause of disease through a similar route. E. coli was traditionally used in the lab as a control for the A. tumefaciens experiments because it did not bind to the plant host, so E. coli studies quickly began. Matthysse found that salad leaves and sprouts encountered bacteria in multiple situations:  contamination of irrigation water or equipment, improperly prepared manure fertilizer, and in post-harvest situations. Once the bacteria are bound, they cannot be removed simply by washing; infected sprouts and fruits that are not cooked prior to eating pose the greatest risk for transferring the disease to humans.

It turns out that the signals produced by the plant cell stimulate bacterial binding for A. tumefaciens, E. coli, and Salmonella. There are multiple ways that A. tumefaciens,  E. coli, and Salmonella appear to be binding to alfalfa sprouts and other salad vegetables. However, studies show that there might be a single sensory pathway that could be blocked so the bacteria are unaware of the presence of a plant in their vicinity. Thus, although the bacteria are ultimately unable to be removed once bound to the plant tissue, the sensory pathway approach could bypass this problem and prevent the bacteria from ever binding in the first place (Figure 3). Currently, Matthysse is looking at multiple methods of blocking/changing signals from plants and/or altering signal receptors on pathogenic bacteria. It might be possible to manipulate the environment so that sensory genes are turned on too soon or too late, and thus attachment and infection are not as effective.

The future of these studies remains promising, and Matthysse acknowledges the difficulty and importance of designing the most effective experiments:  identifying which factors matter the most, pinpointing the best incubation time, appropriating growth temperatures, and other conditions are a serious time investment. Practicality also has to be considered in this situation; increasing costs to customers is not a helpful option when considering long-term reduction in E. coli and Salmonella infections in raw salad vegetables. Eating leafy greens has always seemed very healthy and beneficial to the human diet, but these foods are just as prone to contamination as others. It is probably not common to consider the conditions of our salad, given that it is purchased from a seemingly safe grocery store. “We have all gotten so far away from where our food actually comes from,” Matthysse says.

Ultimately, Matthysse’s studies could lead to revolutionary improvements in genetically modified foods, and the possibilities for utilizing the A. tumefaciens gene transfer mechanism are endless. Her experiments to prevent the binding of pathogens like E. coli and Salmonella to salad vegetables could significantly reduce the number of outbreaks of these pathogens. Understanding these complicated interactions will continue to provide a strong foundation for future studies of plant pathogens.

Escherichia coli, a Gram-negative bacterium widely studied in the lab as a model organism and also found in cases of food poisoning
Figure 2: Escherichia coli, a Gram-negative bacterium widely studied in the lab as a model organism and also found in cases of food poisoning
Attachment of Agrobacterium tumefaciens to tomato root hairs. The decrease in binding visible from (A) to (B) is a comparison of wildtype A. tumefaciens (A) to A. tumefaciens without the attachment mediating gene, UPP(B).
Figure 3: Attachment of Agrobacterium tumefaciens to tomato root hairs. The decrease in binding visible from (A) to (B) is a comparison of wildtype A. tumefaciens (A) to A. tumefaciens without the attachment mediating gene, UPP(B).
Dr. Ann Matthysse, Professor of Biology, University of North Carolina at Chapel Hill.
Dr. Ann Matthysse, Professor of Biology, University of North Carolina at Chapel Hill.

References:

  1. Ann G. Matthysse; Frontiers in Plant Science 2014, 5, 1-8.
  2. Interview with Ann G. Matthysse, Ph.D. 9/18/2014.
  3. Update on Multi-State Outbreak of E. coli O157:H7 Infections From Fresh Spinach, October 6, 2006. http://www.cdc.gov/ecoli/2006/september/updates/100606.htm. (accessed September 22, 2014).

Image Sources:

  1. A. tumefaciens and E. coli: Public Domain
  2. Figure 3: Ann Matthysse

This article was previously published in Carolina Scientific Magazine, Fall 2014.