Engineering, MSU - Bozeman
This is a story on a war of epic proportions, one that improbably begins with entities you can’t even see.
On a global basis, the enemy, antibiotic-resistant bacteria, is killing people every minute of every day, and by 2050, antibiotic-resistant infections are projected to become the world’s leading cause of death, killing at least 10 million people each year while also dealing a cumulative $100 trillion blow to the world economy.
Dr. Tom Frieden, former director of the U.S. Centers for Disease Control and Prevention (CDC), even dubbed one particularly dangerous group of bacteria as “the nightmare bacteria.” Known by the acronym CRE, it is impervious to almost all currently approved antibiotics, and infections result in a high rate of death—regardless of the patient’s age or health status.
Thankfully, awareness of their threat is growing. According to a Pew poll published in April 2020, Americans now rank the spread of infectious diseases as the No. 1 global threat to humanity, ranked even higher than the risks posed by nuclear weapons, terrorism and climate change.
For good reason: Bacteria cause millions of life-threatening infections in people each year, and are so remarkably adaptable they thrive in almost every environment on Earth, including some of the most inhospitable reaches of the planet. In a form we now know as “bacterial biofilms,” they even inhabit the steaming, acidic pools of Yellowstone National Park and the deepest trenches of the oceans, an environment with intensely crushing pressures, where neither light nor oxygen penetrate.
It should come as no surprise then, that bacterial biofilms are able to persist for long periods of time in hospital environments, naively thought to be total medical safe havens.
As if the terrestrial fitness of bacteria wasn’t enough to give pause, their success in space has also been notable, as biofilms were apparently “rampant” on the Russian space station, Mir. It was determined that bacterial biofilms were to blame for eating away at both the functional and structural integrity of the Russian space station. They are similarly a challenge on the International Space Station. It’s an astonishing reality that the microgravity conditions present in outer space actually stimulate biofilm formation, which is the bacterial response to almost any form of stress.
An urgent question arises: What is a biofilm, and how do biofilms pose a risk to people?
“In essence, when bacteria detect a surface, whether living or inanimate, they immediately adhere to it and form a biofilm,” said Dr. Brett Baker, a resident of Big Sky, and founder, president and chief scientific officer of Bozeman’s Microbion Corporation.
What happens next, explains Baker, truly humbles any horror flick: After forming a biofilm, the level of antibiotic- resistance increases up to several thousand-fold, encasing large numbers of bacteria in a plastic-like polymer substance that acts as a bacterial protective shield. Worse, because of a high mutation rate fostered by biofilms, they develop antibiotic- resistance rapidly.
“Biofilms are now known to cause most infections caused by medical devices, which account for the majority of deadly infections acquired in hospitals,” stated Baker. “The National Institutes of Health has stated that up to 80 percent of all bacterial infections are biofilm-related. Our growing awareness of bacterial biofilms represents a very recent revolution in the science of microbiology.”
Prior to the year 1990, less than 50 scientific papers were published on the subject of biofilms and infectious diseases, yet from 1990 to the present day, a search on Medline results in over 14,000 scientific papers relating biofilms to infectious diseases and antibiotic-resistance.
Montana plays a central role in this story. The term biofilm was first coined in the late-1970s, when Dr. Bill Costerton, former director of Montana State University’s Center for Biofilm Engineering (CBE) in Bozeman, made landmark discoveries as to their biology and functionality. Until Costerton introduced biofilms to the world, the science of microbiology had essentially been unaware of this challenging and highly resistant form of bacteria. Leadership of the CBE was then passed to Dr. Phil Stewart who led the Center until 2015, and was named an MSU Regents Professor in 2019—he authored more than 185 peer-reviewed publications on biofilms which have been cited more than 40,000 times, making him the most-cited researcher at MSU.
Biofilms are known, for instance, to play a significant role in life-threatening bacterial lung infections that can occur when patients are placed on mechanical ventilators. Ventilator-associated pneumonia, or VAP, represents a life-threatening risk, for instance, for patients placed on mechanical ventilation in the COVID-19 pandemic.
“By 2050, antibiotic-resistant infections are projected to become the world’s leading cause of death, killing at least 10 million people each year.”
In 2008, Dr. Anthony Fauci, the raspy-voiced medical professional at the forefront of public-facing expertise during this evolving crisis, published a paper that found “the vast majority” of deaths from the Spanish Flu of 1918-19 (as well as the pandemics that occurred in 1957 and 1968), were actually caused by secondary bacterial infections, also known as “bacterial superinfections,” which formed a deadly combination with the underlying viral infections. Some estimates put 50-100 million dead worldwide from the Spanish Flu pandemic. In his paper, Dr. Fauci strongly recommended that to effectively prepare for pandemics, it is critical to develop antibiotics to treat the deadly bacterial infections that accompany widespread viral infections, in addition to the development of vaccines and anti-viral drugs.
Consistently during viral pandemics over the last century, viruses were not usually the primary cause of death. Instead bacteria lready present in the upper respiratory tract opportunistically infected patients whose lungs were damaged by viruses, and it was the bacterial infection that often proved deadly. Now, according to Baker, newly published COVID-19 research is suggesting that history may be repeating itself. One recent paper on COVID-19 reported that 50 percent of patients in the study suffered from bacterial superinfections. Similarly, up to 55 percent of the deaths from the H1N1 pandemic of 2009 are attributed to bacterial superinfections.
As communities around the globe battle the COVID-19 viral pandemic, fear and uncertainty have gripped every facet of life, shuttering doors, stalling economies and bringing humanity to its knees. According to Baker, one way to help reduce the risk of death during a viral pandemic is through the development of innovative antibiotics and anti-infective strategies, preventing and treating bacterial superinfections. Pandemics present an urgent need for both antiviral and antibacterial drugs. The mission of Microbion is to prevent the deaths caused by antibiotic-resistant bacteria and their biofilms—whether during pandemics, or during non-pandemic times.
Antibiotic-resistant bacterial infections kill over 700,000 people each year on a global basis, and we are witnessing rates of antibiotic-resistance continue to mount. Even a brand new ventilator can be rendered useless in this fight when antibiotic-resistant bacteria form biofilms on the internal surfaces of the ventilator. This can lead to portions of biofilm breaking off from the tubing to be breathed in, lodging deep in the patient’s lungs.
That’s where Microbion’s team comes in, working as tirelessly as the bacteria they hope to thwart, to advance safe and effective therapies to overcome bacterial and fungal infections, including those caused by biofilms—in other words, the same types of life-threatening superinfections that have increased the death toll in all pandemics over the past over 101 years.
“We live in a microbial world,” Baker emphasized. “Bozeman is truly at the center of solving some of the world’s most pressing infectious disease challenges. We are making ground-breaking advances in biofilms and antibiotic-resistant pathogens, to prevent or reduce their impact on human health.”
Visit microbioncorp.com for an executive summary of a white paper detailing improvements in technology and the effects of biofilms in this latest pandemic.