Comparative virulence of diverse Coxiella burnetii strains

Carrie M Long,Paul A Beare,Diane C Cockrell,Charles L Larson,Robert A Heinzen

doi:10.1080/21505594.2019.1575715

Carrie M Long, Paul A Beare + Show 3 more

Open Access

https://doi.org/10.1080/21505594.2019.1575715

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Abstract

ABSTRACTCoxiella burnetii is an intracellular, gram-negative bacterium that causes the zoonosis Q fever. This disease typically presents as an acute flu-like illness with persistent, focalized infections occurring less frequently. Clinical outcomes of Q fever have been associated with distinct genomic groups of C. burnetii, suggesting that gene content is responsible for virulence potential. To investigate this hypothesis, the virulence of thirteen C. burnetii strains (representing genomic groups I-VI) was evaluated in a guinea pig infection model by intraperitoneal injection. Seven strains caused a sustained fever (at least two days ≥39.5°C) in at least half of the animals within each experimental group. At fourteen days post infection, animals were euthanized and additional endpoints were evaluated, including splenomegaly and serology. The magnitude of these endpoints roughly correlated with the onset, duration, and severity of fever. The most severe disease was caused by group I strains. Intermediate and no virulence were evidenced following infection with group II-V and group VI strains, respectively. Flow cytometric analysis of the mesenteric lymph nodes revealed decreased CD4+ T cell frequency following infection with highly virulent group I strains. These findings buttress the hypothesis that the pathogenic potential of C. burnetii strains correlates with genomic grouping. These data, combined with comparative genomics and genetic manipulation, will improve our understanding of C. burnetii virulence determinants.

Highlights

Coxiella burnetii is a gram-negative, intracellular bacterium with worldwide dissemination [1]
Q fever generally presents as an acute illness marked by flu-like symptoms and high fever, many individuals remain asymptomatic throughout infection
Several Nine Mile strains were utilized as reference strains due to their historic experimental use and known virulence including Nine Mile I RSA493 (NMI), Nine Mile Crazy RSA514 (NM Crazy), and Nine Mile II RSA439 clone 4 (NMII) [18]

Summary

Introduction

Coxiella burnetii is a gram-negative, intracellular bacterium with worldwide dissemination [1]. This bacterium is clinically significant due to its identity as the causative agent of the zoonosis Q fever. Environmental stability, aerosol transmission, and the debilitating nature of Q fever, C. burnetii is considered a potential biological weapon, resulting in its classification as a select agent [2]. Goats, and sheep are the primary reservoirs responsible for human infection which typically occurs following inhalation of infectious aerosols derived from these animals and their products. Q fever generally presents as an acute illness marked by flu-like symptoms and high fever, many individuals remain asymptomatic throughout infection. Full recovery is common following acute illness, after antibiotic treatment. Some patients may develop persistent focalized infections (formerly referred to as “chronic Q fever”) such as endocarditis, hepatitis, lymphadentitis, myocarditis, osteomyelitis, and/or vascular infection [3,4]

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