O-antigen loss helps Klebsiella pneumoniae survive meropenem stress

Loss of the O-antigen, a surface sugar structure of Klebsiella pneumoniae, can strengthen the bacterium’s resistance to the last-line antibiotic meropenem, according to a study published in Nature Communications. The researchers found that prolonged exposure to subinhibitory levels of meropenem promoted O-antigen loss, most often through insertion sequences disrupting genes involved in O-antigen biosynthesis.

The work addresses a persistent problem in treating multidrug-resistant Gram-negative infections. Carbapenems such as meropenem are reserved as last-line beta-lactam antibiotics, yet the adaptive routes by which Enterobacterales survive carbapenem stress remain incompletely understood. The new findings identify surface remodeling as one such route.

According to the study, O-antigen deficiency was accompanied by envelope-associated redox remodeling and reprogramming of central metabolism. These changes mitigated the accumulation of reactive oxygen species induced by meropenem, reducing oxidative killing of the bacteria. In other words, the surface change did not simply alter drug entry; it reshaped how the cell handled the metabolic and oxidative consequences of antibiotic stress.

The adaptation carried a trade-off. O-antigen-deficient bacteria showed collateral sensitivity to aminoglycosides, a different antibiotic class. The researchers linked this vulnerability to increased outer-membrane electronegativity and altered porin expression, which may promote aminoglycoside uptake. The authors note that this aminoglycoside vulnerability warrants further evaluation.

The authors conclude that O-antigen deficiency acts as a surface-remodeling adaptation that enhances carbapenem resistance through coordinated metabolic and redox reprogramming, while simultaneously exposing a targetable weakness. The study was published as an open-access article on 22 October 2026.

Subject of Research: How O-antigen loss reprograms metabolism and redox balance to alter carbapenem resistance in Klebsiella pneumoniae

Article Title: O-antigen loss modulates meropenem resistance in Klebsiella pneumoniae through metabolic and redox reprogramming

Article References: Huang, J., Wei, D.-W., Song, Y., Vollmer, D., Tian, X., Zhou, T., Liang, J., Jing, S., Zhang, G., Wang, C., Zhu, J., Vollmer, W., & Feng, J. (2026). O-antigen loss modulates meropenem resistance in Klebsiella pneumoniae through metabolic and redox reprogramming. Nature Communications. https://doi.org/10.1038/s41467-026-78472-2

Image Credits: AI Generated

DOI: 10.1038/s41467-026-78472-2

Keywords: Klebsiella pneumoniae, meropenem, carbapenem resistance, O-antigen, reactive oxygen species, aminoglycosides, collateral sensitivity, outer membrane, metabolic reprogramming, insertion sequence, antimicrobial resistance, loss