Imagine a silent killer lurking in hospitals, defying our best medicines. That's the stark reality of Acinetobacter baumannii (A. baumannii), a bacterium rapidly evolving resistance to antibiotics and endangering countless lives. In the United States, a staggering number of patients – more than one in every hundred – find themselves battling infections caused by this formidable foe.
A. baumannii's remarkable ability to adapt and develop resistance stems from its dynamic genome. This adaptability is what makes it such a challenge to treat. As Andrei Osterman, PhD, a professor at Sanford Burnham Prebys Medical Discovery Institute, puts it, "This is a deadly pathogen that is notorious for its resistance to traditional drugs." He is also the Vice Dean and Associate Dean of Curriculum in the Graduate School of Biomedical Sciences.
And the situation is getting worse. Previous studies have revealed a chilling statistic: one-third of A. baumannii infections acquired in U.S. hospitals are resistant to carbapenem, a commonly used antibiotic. What’s truly devastating is that patients with these drug-resistant infections face a significantly higher risk of death during their hospital stay, longer hospitalizations, and are more likely to be transferred to other healthcare facilities instead of returning home. This resistance not only prolongs suffering but also strains our healthcare system.
But here's where it gets controversial... Some argue that the overuse of antibiotics in agriculture and livestock contributes significantly to the rise of antibiotic-resistant bacteria like A. baumannii, a claim that sparks heated debate between public health officials and the agricultural industry. What do you think? Is there a direct line between antibiotic use in farming and the growing threat in our hospitals? Let us know your thoughts in the comments.
Now, a team of scientists at Sanford Burnham Prebys, in collaboration with Roche Pharmaceuticals, is fighting back. They've published groundbreaking findings in Antimicrobial Agents and Chemotherapy (October 29, 2025) showcasing an experimental approach to mapping the genetic mutations that enable A. baumannii to resist two less commonly used antibiotics.
"Tigecycline and colistin are part of physicians' last line of defense for A. baumannii infections," explains Dr. Osterman, the lead author of the study. "Because they are rarely used in the U.S. and existing resistance is comparatively low, but rising, which prompted us to study how the bacteria acquire new antibiotic resistances." This research provides critical insight into how these "last resort" antibiotics are losing their effectiveness.
The team employed a sophisticated device called a morbidostat. Imagine a continuously evolving bacterial culture under constant pressure. The morbidostat does just that: it allows bacteria to grow continuously over multiple generations while being exposed to gradually increasing concentrations of antibiotics. A computer monitors the culture's growth and automatically increases the antibiotic dosage as long as the culture thrives.
“It works like an evolution machine that more closely mimics the conditions in the human body versus other methods,” Osterman stated. This method offers a more realistic representation of how resistance develops within a patient's body compared to traditional laboratory settings. And this is the part most people miss... The morbidostat allows researchers to observe evolution in real-time, capturing the subtle genetic changes that lead to resistance, something static experiments can't achieve.
"When combined with genomic sequencing, this approach allows us to achieve our goal of creating as comprehensive a map as possible of all theoretically possible mutations that offer resistance to the drugs," Osterman added. By combining the morbidostat with genomic sequencing, the researchers were able to pinpoint the specific genetic changes that allow A. baumannii to survive and thrive in the presence of these antibiotics. This comprehensive mapping effort is crucial for developing strategies to combat resistance.
The scientists' meticulous mapping confirmed and expanded upon existing knowledge of the primary resistance mechanisms for each antibiotic class. For tigecycline, the main driver of acquired resistance was mutations affecting efflux pumps. Think of efflux pumps as tiny bouncers that kick out unwanted guests from a nightclub. In this case, the "unwanted guest" is the antibiotic, and the efflux pumps actively remove the drug from the bacterial cell before it can cause damage. This is a well-established resistance mechanism, but the study broadened our understanding of the specific mutations involved in A. baumannii.
The second major area of resistance was linked to colistin. The team identified mutations that affect the activity of an enzyme that prevents colistin from reaching its target – a vital component of the bacterial cell wall. By disrupting this enzyme, the bacteria effectively shields itself from the antibiotic's attack.
What implications does this have for treatment? Well, as Osterman explains, "Once we have a complete map of most possible mutations that provide resistance, we can compare this map with other sequenced genomes to make predictions, including sequences from patients suffering from A. baumannii infections." The researchers analyzed over 10,000 publicly available A. baumannii genomes, allowing them to identify patterns and predict which strains are likely to be resistant to specific antibiotics.
The ultimate goal is to translate this research into practical applications in hospitals and clinics. The team envisions a future where genomics-based predictions of drug resistance and susceptibility guide treatment decisions. "A serious problem occurs when patients are treated by trial and error and given an antibiotic the bacteria are already resistant or even partially resistant to," Osterman points out. "This further promotes bacterial resistance, and you lose time that patients don't always have."
The ability to quickly identify effective antibiotics would be a game-changer. "The data we are accumulating would allow physicians to order a sequencing test and prescribe an antibiotic the bacteria are least likely to resist, which will be good for individual patients and, more globally, help us slow down the overall evolution of antibiotic resistance." This personalized approach to antibiotic therapy could significantly improve patient outcomes and help curb the spread of antibiotic-resistant bacteria. But here's a question for you: with the increasing sophistication of bacterial resistance, will we ever truly win the war against superbugs, or are we destined to always be one step behind? Share your thoughts below.
