Gaining a better understanding of the genome of the bacterium responsible for Q fever

[Sly Saint]

ANSES's Sophia Antipolis Laboratory has participated in a vast genetic analysis of strains of Coxiella burnetii, the bacterium responsible for Q fever, a disease that can be transmitted to humans. This collaboration between animal and human disease specialists, on which a paper was published in late 2022, is the first step in a One Health project on this zoonosis.

Q fever can be transmitted from animals to humans, where it can cause a severe flu-like illness with possible liver or lung complications. In rare cases, the disease may become chronic and cause conditions such as endocarditis or chronic fatigue syndrome. The main reservoirs of this zoonosis are ruminant farms. This is the main source of infection for humans, with human-to-human transmission of Q fever being rare.

A collaboration involving both animal and human health
The study, published in November 2022 in the journal Frontiers in Microbiology, results from a collaboration between the Animal Q Fever Unit of ANSES's Sophia Antipolis Laboratory, which is both the national reference laboratory (NRL) and World Organisation for Animal Health (WOAH) reference laboratory, and the national reference centre (NRC) for Q fever hosted by the Méditerranée Infection University Hospital Institute in Marseille. The NRL is responsible for the animal aspects of Q fever, while the NRC focuses on the human side.

ANSES provided whole genome sequences of C. burnetii strains isolated from ruminants. These strains were added to the collection of patient-derived bacteria held by the NRC. The research carried out by the two partners constitutes the world's most comprehensive genetic analysis of Coxiella burnetii: 75 genomes were sequenced, including 65 new ones.

By comparing the genomes of all the strains, the bacterium's pangenome was obtained, i.e. the parts of the genome common to all strains. The researchers also deciphered specific parts of certain strains and showed that some were linked to particular clinical signs or geographical areas.

https://www.anses.fr/en/content/bacterium-q-fever

 

[Hutan]

https://www.frontiersin.org/articles/10.3389/fmicb.2022.1022356/full
Pangenomic analysis of Coxiella burnetii unveils new traits in genome architecture
Abdallah et al, a French study

Coxiella burnetii is the etiological agent of Q fever, a worldwide zoonosis able to cause large outbreaks. The disease is polymorphic. Symptomatic primary infection is named acute Q fever and is associated with hepatitis, pneumonia, fever, and auto-immune complications while persistent focalized infections, mainly endocarditis, and vascular infections, occur in a minority of patients but are potentially lethal. In order to evaluate the genomic features, genetic diversity, evolution, as well as genetic determinants of antibiotic resistance, pathogenicity, and ability to cause outbreaks of Q fever, we performed a pangenomic analysis and genomic comparison of 75 C. burnetii strains including 63 newly sequenced genomes.

Our analysis demonstrated that C. burnetii has an open pangenome, unique genes being found in many strains. In addition, pathogenicity islands were detected in all genomes. In consequence C. burnetii has a high genomic plasticity, higher than that of other intracellular bacteria. The core- and pan-genomes are made of 1,211 and 4,501 genes, respectively (ratio 0.27). The core gene-based phylogenetic analysis matched that obtained from multi-spacer typing and the distribution of plasmid types. Genomic characteristics were associated to clinical and epidemiological features. Some genotypes were associated to specific clinical forms and countries. MST1 genotype strains were associated to acute Q fever.

A significant association was also found between clinical forms and plasmids. Strains harboring the QpRS plasmid were never found in acute Q fever and were only associated to persistent focalized infections. The QpDV and QpH1 plasmids were associated to acute Q fever. In addition, the Guyanese strain CB175, the most virulent strain to date, exhibited a unique MST genotype, a distinct COG profile and an important variation in gene number that may explain its unique pathogenesis. Therefore, strain-specific factors play an important role in determining the epidemiological and clinical manifestations of Q fever alongside with host-specific factors (valvular and vascular defects notably).

 

[Hutan]

This is an interesting study, demonstrating the power of genetics to predict the clinical impact of a pathogen.

Sadly, despite the article mentioning chronic fatigue syndrome, I didn't see that, or Q fever fatigue syndrome, mentioned at all in the paper, not even in the list of possible consequences of a Coxiella burnetii infection. I guess an issue is that it may not be possible to isolate a strain from a person who has Q fever fatigue syndrome in the same way that strains grown from damaged removed heart valves are. Nevertheless, it would be very interesting to do a prospective study - describing the genomic content of C. burnetii in different outbreaks, and then tracking the percentage of people who go on to develop Q fever fatigue syndrome.

I think the potential to use genomics not just on the human side, but also on the pathogen side to identify characteristics that make a post-infection fatigue syndrome(for want of a better word) possible and/or more likely could really move our understanding of ME/CFS forward.