When Alexander Fleming discovered penicillin in 1928, it started a new era in medicine: the era of antibiotics. Once penicillin could be efficiently purified in bulk in the 1940’s, it gave doctors access to an incredibly powerful tool to cure previously deadly diseases such as pneumonia and gonorrhea. However, antibiotics did not quite turn out to be a class of miracle drugs. Over time, many bacteria have been able to able to adapt to antibiotic treatment and develop resistance to the drugs. This has created an arms race between pharmaceutical companies and bacteria; as bacteria strains become resistant to antibiotics, drug companies must work to develop new medicines to fight them. In some cases, the bacteria seem to be winning. According to the CDC, more than 2 million people are infected by antibiotic-resistant bacteria in the US annually and 23,000 people die from drug-resistant infections every year. Most of these bacteria are only resistant to certain classes of antibiotics, although there have been almost 10 cases of totally-resistant bacteria in the US so far.
While the number of cases of bacteria that are completely resistant to all known antibiotic drugs is low, this is a nightmare scenario for health care. To develop a new last line of defense against antibiotic-resistant strains, researchers are looking to fight bacteria with…other bacteria. The plan is to harness bacteria that naturally prey on other bacteria, and use these predators to attack infections within the human body. Scientists are studying a strain of bacteria called Bdellovibrio bacteriovorus to this end. B. bacteriovorus attacks “gram-negative” bacteria, i.e. bacteria that have both an inner cell membrane and an outer cell wall. Many of the most dangerous antibiotic-resistant bacterial strains are gram-negative, such as the Enterobacteriaceae family (which includes pathogens such as Salmonella and E. coli) including Shigella spp (which causes dysentery).
B. bacteriovorus attacks these bacteria by forcing itself in between the cell wall and inner membrane. Once inside, it secretes enzymes that break down the host’s cell structure, including the DNA. B. bacteriovorus uses the broken-down proteins to assemble copies of itself, destroying the host in the process. Researchers have targeted this bacterium for several reasons. First, B. bacteriovorus does not attack mammalian cells, so it could be safe for use in humans. Also, since it attacks its prey using brute force, it is impossible for other bacteria to develop any type of systematic resistance to it like they could for a drug. Last, since the prey’s DNA is destroyed in the attack, there is no risk of leftover DNA being absorbed by other bacteria. This is important, since this is one of the ways that drug-resistance can currently be transferred between bacterial species.
To test B. bacteriovorus as a potential treatment option, the researchers studied its performance in zebrafish. Zebrafish are a valuable study organism since they are transparent: the whole infection and treatment process can be observed by microscope. The researchers gave zebrafish larvae a lethal dose of a strain of Shigella flexneri (which causes diarrhea in humans) that was resistant to antibiotics. The scientists found that the fish that received an injected B. bacteriovorus treatment had a much larger survival rate compared to fish that didn’t receive the treatment; the S. flexneri levels in the treated fish dropped 98% within 48 hours. Since B. bacteriovorus works so fast (the entire predatory cycle lasts 3-4 hours), they can quickly reduce the infection to a level that the zebrafish’s immune system could handle.
So, are these bacteria a miracle cure for antibiotic-resistant bacterial infections? Scientists still don’t know. They expect at the spend another decade studying the effects of B. bacteriovorus in animals before they move on to human trials. Even then, these treatments would not be benign; this type of drug would likely have some very severe side effects. However, it would represent a life-saving option in the event that more bacterial strains developing comprehensive antibiotic resistance.
Our refrigerated incubators are well suited for zebrafish research. These chambers have a temperature range of 2-50°C. The chambers are very versatile and can be adapted to create environments requiring vibration resistance, complete darkness, intense lighting, or a combination of variables. A microprocessor controls and displays the chamber temperature, and high and low temperature mechanical failsafes protect chamber contents in the unlikely event of a temperature excursion. For the lighting in our chambers, we use cool white (4100K color) LED lights. Coincidentally, the light from these LEDs is most intense in the blue spectrum that is favorable for zebrafish rearing.