Natural reversion promotes LPS elongation in an attenuated Coxiella burnetii strain

Carrie M. Long (), Paul A. Beare, Diane Cockrell, Picabo Binette, Mahelat Tesfamariam, Crystal Richards, Matthew Anderson, Jessica McCormick-Ell, Megan Brose, Rebecca Anderson, Anders Omsland, Talima Pearson and Robert A. Heinzen
Additional contact information
Carrie M. Long: National Institutes of Health
Paul A. Beare: National Institutes of Health
Diane Cockrell: National Institutes of Health
Picabo Binette: National Institutes of Health
Mahelat Tesfamariam: National Institutes of Health
Crystal Richards: National Institutes of Health
Matthew Anderson: National Institutes of Health
Jessica McCormick-Ell: National Institutes of Health
Megan Brose: National Institutes of Health
Rebecca Anderson: National Institutes of Health
Anders Omsland: Washington State University
Talima Pearson: Northern Arizona University
Robert A. Heinzen: National Institutes of Health

Nature Communications, 2024, vol. 15, issue 1, 1-8

Abstract: Abstract Lipopolysaccharide (LPS) phase variation is a critical aspect of virulence in many Gram-negative bacteria. It is of particular importance to Coxiella burnetii, the biothreat pathogen that causes Q fever, as in vitro propagation of this organism leads to LPS truncation, which is associated with an attenuated and exempted from select agent status (Nine Mile II, NMII). Here, we demonstrate that NMII was recovered from the spleens of infected guinea pigs. Moreover, these strains exhibit a previously unrecognized form of elongated LPS and display increased virulence in comparison with the initial NMII strain. The reversion of a 3-bp mutation in the gene cbu0533 directly leads to LPS elongation. To address potential safety concerns, we introduce a modified NMII strain unable to produce elongated LPS.

Date: 2024
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DOI: 10.1038/s41467-023-43972-y

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