Bacterial sialidases subvert the complement system through desialylation
4 affiliations
- 1Department of Oral Craniofacial Molecular Biology, Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia, USA.
- 2Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, the State University of New York, Buffalo, New York, USA.
- 3Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, New York, USA.
- 4Department of Biological Sciences, Hunter College of City University of New York, New York City, New York, USA.
Abstract
Bacterial sialidases (neuraminidases) are widely studied virulence factors, yet their impact on the complement system, a central component of innate immunity, remains poorly understood. Here, we investigate the effects of six sialidases from five human pathogens, including Bacteroides fragilis, Clostridium perfringens, Tannerella forsythia, Treponema denticola, and Vibrio cholerae on complement immunity using an integrated approach combining genetics, biochemistry, glycobiology, mass spectrometry, and structural biology. We show that major complement proteins, including C1q, C4, and C5, as well as complement regulators Factor I, Factor H, and C4BP, are modified by terminal sialic acids (sialylation) and undergo terminal desialylation by all six sialidases. Using the oral pathogen T. denticola and its sialidase NanH as a representative model, we demonstrate that sialidase-mediated desialylation suppresses complement activation and surface deposition, promoting complement evasion. Structural analyses of T. denticola NanH in complex with an inhibitor, sialic acid, and native glycans, together with comparisons to other sialidase structures, reveal the molecular basis of substrate recognition and catalysis. Despite substantial sequence diversity, all six exo-α-sialidases share a conserved six-bladed β-propeller catalytic domain and cleave both N-acetylneuraminic acid and N-glycolylneuraminic acid, the predominant mammalian sialic acids. Together, these findings establish a conserved structural and functional mechanism by which diverse bacterial pathogens desialylate complement components to impair innate immune defense.
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BibTeX
@article{kurniyati2026bacterial,
title = {{Bacterial sialidases subvert the complement system through desialylation}},
author = {Kurni Kurniyati and Nicholas D Clark and Qin Fu and Sheng Zhang and Weigang Qiu and Michael G Malkowski and Chunhao Li},
journal = {Protein science : a publication of the Protein Society},
year = {2026},
month = oct,
doi = {10.1002/pro.70834},
url = {https://europepmc.org/article/PMC/PMC13717605},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bacterial sialidases subvert the complement system through desialylation
AU - Kurni Kurniyati
AU - Nicholas D Clark
AU - Qin Fu
AU - Sheng Zhang
AU - Weigang Qiu
AU - Michael G Malkowski
AU - Chunhao Li
PY - 2026
DA - 2026/10/29
JO - Protein science : a publication of the Protein Society
DO - 10.1002/pro.70834
UR - https://europepmc.org/article/PMC/PMC13717605
AB - Bacterial sialidases (neuraminidases) are widely studied virulence factors, yet their impact on the complement system, a central component of innate immunity, remains poorly understood. Here, we investigate the effects of six sialidases from five human pathogens, including Bacteroides fragilis, Clostridium perfringens, Tannerella forsythia, Treponema denticola, and Vibrio cholerae on complement immunity using an integrated approach combining genetics, biochemistry, glycobiology, mass spectrometry, and structural biology. We show that major complement proteins, including C1q, C4, and C5, as well as complement regulators Factor I, Factor H, and C4BP, are modified by terminal sialic acids (sialylation) and undergo terminal desialylation by all six sialidases. Using the oral pathogen T. denticola and its sialidase NanH as a representative model, we demonstrate that sialidase-mediated desialylation suppresses complement activation and surface deposition, promoting complement evasion. Structural analyses of T. denticola NanH in complex with an inhibitor, sialic acid, and native glycans, together with comparisons to other sialidase structures, reveal the molecular basis of substrate recognition and catalysis. Despite substantial sequence diversity, all six exo-α-sialidases share a conserved six-bladed β-propeller catalytic domain and cleave both N-acetylneuraminic acid and N-glycolylneuraminic acid, the predominant mammalian sialic acids. Together, these findings establish a conserved structural and functional mechanism by which diverse bacterial pathogens desialylate complement components to impair innate immune defense.
SN - 0961-8368
SN - 1469-896X
ER -