Deep inside a New Jersey lab, scientists are waging a quiet war against some of the most dangerous enemies in modern medicine: superbugs that resist nearly every antibiotic we throw at them. The laboratory of Barry N. Kreiswirth, Ph.D., at the Hackensack Meridian Center for Discovery and Innovation (CDI) just published three new studies in the journal Antimicrobial Agents and Chemotherapy that map exactly how these bacteria survive—and how we might finally beat them.
The good news hiding in these papers is a simple idea: bacteria pay a price for their defenses. In the first study, the team used a tool called transposon sequencing, or TnSeq, to scan the genes that control how vulnerable a stubborn germ called carbapenem-resistant Klebsiella pneumoniae truly is. Led by Zhichen Zhu, Liang Chen of the University at Buffalo, and Kreiswirth, the team discovered something surprising. When superbugs change their outer surface to escape the viruses that hunt them (phages), they lose their shields against our last-line drugs. Removing those surface receptors made the bacteria vulnerable again to powerful antibiotics like meropenem, colistin, and cefiderocol. In other words, a superbug that outsmarts one threat may leave itself naked to another.
The second paper tackled cefiderocol, a clever drug that sneaks inside bacteria by pretending to be food they need to pull in iron. The scientists, led by Kevin J. Rome, Austin J. Terlecky, and Kreiswirth, found that resistant "superbugs" build a layered defense network to block this trick, relying on genes like blaKPC-3. Deleting that single gene made the bacteria four times easier to kill with the drug. That fourfold drop shows how even a little bit of resistance can matter enormously when drug levels inside the cell are low—and how removing one piece of the armor can bring the whole defense down.
The third study moved from the lab bench to the hospital bedside. Researchers followed 159 patients with acute leukemia and a related bone-marrow condition called myelodysplastic syndrome as they went through chemotherapy. During a dangerous window called neutropenia—when the body's infection-fighting white blood cells crash to near zero—one in five patients who carried resistant gut bacteria developed a matching bloodstream infection. Whole-genome sequencing confirmed a stunning 100% match between the bacteria colonizing their bodies and the strains causing infections in their blood. That proof means doctors can screen patients ahead of time and give targeted antibiotics only to those who truly need them, avoiding the blanket overuse that fuels even more resistance.
David Perlin, the CDI's chief scientific officer, put it plainly: by linking molecular genetics, genomics, and real-world clinical care, Kreiswirth's lab keeps uncovering the rules of bacterial survival—rules that point the way to better outcomes for patients. The fight is far from over, but these three studies show that if we learn how superbugs outsmart us, we can learn how to outsmart them right back.