Cell-Free Propagation of Coxiella burnetii Does Not Affect Its Relative Virulence

Kuley, Runa; Smith, Hilde E.; Frangoulidis, Dimitrios; Smits, M.A.; Roest, H.I.J.; Bossers, Alex

doi:10.1371/journal.pone.0121661

Cited by 20 publications

(25 citation statements)

References 50 publications

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“…Differences between strains in the induction of IL-10 may also be one of the virulence factors of C. burnetii. In a mouse model of Q fever, the Nine Mile strain appeared to be more virulent than the 3262 strain (22). Notably, in the presence of C. burnetii IgG phase I antibodies, this shift toward higher IL-10 production was absent.…”

Section: Discussionmentioning

confidence: 95%

Viable Coxiella burnetii Induces Differential Cytokine Responses in Chronic Q Fever Patients Compared to Heat-Killed Coxiella burnetii

Jansen¹,

Dinkla

Roest

et al. 2018

Infect Immun

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Cytokine responses of chronic Q fever patients to the intracellular bacterium have mostly been studied using stimulation of immune cells with heat-killed due to the extensive measures needed to work with viable biosafety level 3 agents. Whether research with heat-killed can be translated to immune responses to viable is imperative for the interpretation of previous and future studies with heat-killed Peripheral blood mononuclear cells (PBMCs) of chronic Q fever patients ( = 10) and healthy controls ( = 10) were stimulated with heat-killed or viable of two strains, Nine Mile and the Dutch outbreak strain 3262, for 24 h, 48 h, and 7 days in the absence or presence of serum containing anti- antibodies. When stimulated with viable , PBMCs of chronic Q fever patients and controls produced fewer proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, and IL-1β) after 24 h than after stimulation with heat-killed In the presence of Q fever seronegative serum, IL-10 production was higher after stimulation with viable rather than heat-killed ; however, when incubating with anti- antibody serum, the effect on IL-10 production was reduced. Levels of adaptive, merely T-cell-derived cytokine (gamma interferon, IL-17, and IL-22) and CXCL9 production were not different between heat-killed and viable stimulatory conditions. Results from previous and future research with heat-killed should be interpreted with caution for innate cytokines, but heat-killed -induced adaptive cytokine production is representative of stimulation with viable bacteria.

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Section: Discussionmentioning

confidence: 95%

Viable Coxiella burnetii Induces Differential Cytokine Responses in Chronic Q Fever Patients Compared to Heat-Killed Coxiella burnetii

Jansen¹,

Dinkla

Roest

et al. 2018

Infect Immun

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“…Repeated in vitro passages of C. burnetii strains have been shown to induce antigenic variation and loss of virulence characteristics due to the transition into a truncated LPS structure. This truncation of LPS is associated with chromosomal deletions of O-antigen coding genes, located in a 38 kb region in the genome resulting in antigenic phase variation from phase I to phase II (Hoover et al, 2002 ; Denison et al, 2007 ; Kuley et al, 2015b ). The genome sequences established in this study, were compared with the LPS encoding region (CBU0676–CBU0706) of NM-phase I (GenBank: AF387640 ) to visualize deletions in the LPS encoding region.…”

Section: Resultsmentioning

confidence: 99%

Genome Plasticity and Polymorphisms in Critical Genes Correlate with Increased Virulence of Dutch Outbreak-Related Coxiella burnetii Strains

et al. 2017

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Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever. During 2007–2010 the largest Q fever outbreak ever reported occurred in The Netherlands. It is anticipated that strains from this outbreak demonstrated an increased zoonotic potential as more than 40,000 individuals were assumed to be infected. The acquisition of novel genetic factors by these C. burnetii outbreak strains, such as virulence-related genes, has frequently been proposed and discussed, but is not proved yet. In the present study, the whole genome sequence of several Dutch strains (CbNL01 and CbNL12 genotypes), a few additionally selected strains from different geographical locations and publicly available genome sequences were used for a comparative bioinformatics approach. The study focuses on the identification of specific genetic differences in the outbreak related CbNL01 strains compared to other C. burnetii strains. In this approach we investigated the phylogenetic relationship and genomic aspects of virulence and host-specificity. Phylogenetic clustering of whole genome sequences showed a genotype-specific clustering that correlated with the clustering observed using Multiple Locus Variable-number Tandem Repeat Analysis (MLVA). Ortholog analysis on predicted genes and single nucleotide polymorphism (SNP) analysis of complete genome sequences demonstrated the presence of genotype-specific gene contents and SNP variations in C. burnetii strains. It also demonstrated that the currently used MLVA genotyping methods are highly discriminatory for the investigated outbreak strains. In the fully reconstructed genome sequence of the Dutch outbreak NL3262 strain of the CbNL01 genotype, a relatively large number of transposon-linked genes were identified as compared to the other published complete genome sequences of C. burnetii. Additionally, large numbers of SNPs in its membrane proteins and predicted virulence-associated genes were identified in all Dutch outbreak strains compared to the NM reference strain and other strains of the CbNL12 genotype. The presence of large numbers of transposable elements and mutated genes, thereof most likely resulted in high level of genome rearrangements and genotype-specific pathogenicity of outbreak strains. Thus, the epidemic potential of Dutch outbreak strains could be linked to increased genome plasticity and mutations in critical genes involved in virulence and the evasion of the host immune system.

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“…O-antigen is the primary surface antigen recognized by Phase I antiserum [25]. Some, but not all, Phase II strains contain a chromosomal deletion eliminating roughly 20 genes associated with sugar metabolism [26][27][28]. Moreover, deep-rough LPS of Phase II strains can be antigenically distinct [29].…”

Section: Coxiella: a Wide-ranging Zoonotic Pathogenmentioning

confidence: 99%

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

et al. 2016

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Invasion of macrophages and replication within an acidic and degradative phagolysosomelike vacuole are essential for disease pathogenesis by Coxiella burnetii, the bacterial agent of human Q fever. Previous experimental constraints imposed by the obligate intracellular nature of Coxiella limited knowledge of pathogen strategies that promote infection. Fortunately, new genetic tools facilitated by axenic culture now allow allelic exchange and transposon mutagenesis approaches for virulence gene discovery. Phenotypic screens have illuminated the critical importance of Coxiella's type 4B secretion system in host cell subversion and discovered genes encoding translocated effector proteins that manipulate critical infection events. Here, we highlight the cellular microbiology and genetics of Coxiella and how recent technical advances now make Coxiella a model organism to study macrophage parasitism.

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Cell-Free Propagation of Coxiella burnetii Does Not Affect Its Relative Virulence

Cited by 20 publications

References 50 publications

Viable Coxiella burnetii Induces Differential Cytokine Responses in Chronic Q Fever Patients Compared to Heat-Killed Coxiella burnetii

Viable Coxiella burnetii Induces Differential Cytokine Responses in Chronic Q Fever Patients Compared to Heat-Killed Coxiella burnetii

Genome Plasticity and Polymorphisms in Critical Genes Correlate with Increased Virulence of Dutch Outbreak-Related Coxiella burnetii Strains

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

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