Pertussis toxin-dependent and -independent protection by Bordetella pertussis against influenza.

Bacterial-viral co-infections are frequent, but their reciprocal effects are not well understood. Here, we examined the effect Bordetella pertussis infection and the role of pertussis toxin (PT) on influenza A virus (IAV) infection and disease. In C57BL/6J mice, prior nasal administration of virulent B.

Intranasal inoculation with confers protection without inducing classical whooping cough in baboons.

Background: The resurgence of whooping cough in many countries highlights the crucial need for a better understanding of the pathogenesis of respiratory infection by . Exposure of baboons to by the intranasal and intra-tracheal routes is a recently described preclinical model that reproduces both infection of humans and whooping cough disease. Here, we tested both intranasal and intranasal+intra-tracheal exposure routes and assessed their impact on disease development and immunity.

Construction and evaluation of a pertactin-deficient live attenuated pertussis vaccine candidate BPZE1 derivative.

Pertussis, mainly caused by Bordetella pertussis, is a severe respiratory disease that can be fatal, especially in young infants. Vaccines, massively implemented since the middle of the last century, have substantially reduced the pertussis incidence, but have not been able to fully control the disease. One of the shortcomings of current pertussis vaccines is their inability to prevent infection by and transmission of B.

Live attenuated Bordetella pertussis vaccine candidate BPZE1 transiently protects against lethal pneumococcal disease in mice.

BPZE1 is a live attenuated vaccine against infection by Bordetella pertussis, the causative agent of whooping cough. It was previously shown that BPZE1 provides heterologous protection in mouse models of disease caused by unrelated pathogens, such as influenza virus and respiratory syncytial virus. Protection was also observed in mouse models of asthma and contact dermatitis.

Suppression of mucosal Th17 memory responses by acellular pertussis vaccines enhances nasal Bordetella pertussis carriage.

Pertussis has made a spectacular rebound in countries that have switched from whole-cell (wPV) to acellular pertussis vaccines (aPV). Here, we show that, unlike wPV, aPV, while protective against lung colonization by Bordetella pertussis (Bp), did not protect BALB/c mice from nasal colonization, but instead substantially prolonged nasal carriage. aPV prevented the natural induction of nasal interleukin-17 (IL-17)-producing and interferon-γ (IFN-γ)-producing CD103 CD44 CD69 CD4-resident memory T (T) cells.

Manufacture of a Stable Lyophilized Formulation of the Live Attenuated Pertussis Vaccine BPZE1.

Current pertussis vaccines protect against disease, but not against colonization by and transmission of , whereas natural infection protects against both. The live attenuated vaccine BPZE1 was developed to mimic immunogenicity of natural infection without causing disease, and in preclinical models protected against pertussis disease and colonization after a single nasal administration. Phase 1 clinical studies showed that BPZE1 is safe and immunogenic in humans when administered as a liquid formulation, stored at ≤-70 °C.

Combined RNAseq and ChIPseq Analyses of the BvgA Virulence Regulator of Bordetella pertussis.

regulates the production of its virulence factors by the two-component system BvgAS. In the virulence phase, BvgS phosphorylates BvgA, which then activates the transcription of virulence-activated genes (s). In the avirulence phase, such as during growth in the presence of MgSO, BvgA is not phosphorylated and the s are not expressed.

Coordinate regulation of virulence and metabolic genes by the transcription factor HbhR in Mycobacterium marinum.

The heparin-binding hemagglutinin (HBHA) is a multifunctional protein involved in adherence of Mycobacterium tuberculosis to non-phagocytic cells and in the formation of intracytosolic lipid inclusions. We demonstrate that the expression of hbhA is regulated by a transcriptional repressor, named HbhR, in Mycobacterium marinum. The hbhR gene, located upstream of hbhA, was identified by screening a transposon insertion library and detailed analysis of a mutant overproducing HBHA.

Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS.

The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg+ phase to avirulent Bvg- or intermediate Bvgi phases, in which no virulence factors or only a subset of them are produced, respectively.

IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine.

BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration to mimic the natural route of infection. Here, we studied the mechanism of BPZE1-induced immunity in the murine nasal cavity in contrast to acellular vaccine (aPV), although both vaccines protected against lung colonization. Transfer of splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naïve mice against lung colonization but not against nasal colonization.

In vivo imaging of bacterial colonization of the lower respiratory tract in a baboon model of Bordetella pertussis infection and transmission.

Recent whooping cough (pertussis) outbreaks in many countries highlight the crucial need for a better understanding of the pathogenesis of Bordetella pertussis infection of the respiratory tract. The baboon is a recently described preclinical model for the study of B. pertussis infection and may be ideal for the evaluation of new pertussis vaccines.

Primary transcriptome analysis reveals importance of IS elements for the shaping of the transcriptional landscape of Bordetella pertussis.

Bordetella pertussis is the causative agent of whooping cough, a respiratory disease still considered as a major public health threat and for which recent re-emergence has been observed. Constant reshuffling of Bordetella pertussis genome organization was observed during evolution. These rearrangements are essentially mediated by Insertion Sequences (IS), a mobile genetic elements present in more than 230 copies in the genome, which are supposed to be one of the driving forces enabling the pathogen to escape from vaccine-induced immunity.

Construction and evaluation of Bordetella pertussis live attenuated vaccine strain BPZE1 producing Fim3.

Pertussis or whooping cough is currently the most prevalent vaccine-preventable childhood disease despite >85% global vaccination coverage. In recent years incidence has greatly increased in several high-income countries that have switched from the first-generation, whole-cell vaccine to the newer acellular vaccines, calling for improved vaccination strategies with better vaccines. We have developed a live attenuated pertussis vaccine candidate, called BPZE1, which is currently in clinical development.

Characterization of a Bvg-regulated fatty acid methyl-transferase in Bordetella pertussis.

The whooping cough agent Bordetella pertussis controls the expression of its large virulence regulon in a coordinated manner through the two-component signal transduction system BvgAS. In addition to the genes coding for bona fide virulence factors, the Bvg regulon comprises genes of unknown function. In this work, we characterized a new Bvg-activated gene called BP2936.

The multifaceted RisA regulon of Bordetella pertussis.

The whooping cough agent Bordetella pertussis regulates the production of its virulence factors by the BvgA/S system. Phosphorylated BvgA activates the virulence-activated genes (vags) and represses the expression of the virulence-repressed genes (vrgs) via the activation of the bvgR gene. In modulating conditions, with MgSO4, the BvgA/S system is inactive, and the vrgs are expressed.

Investigating pertussis toxin and its impact on vaccination.

Whooping cough, caused by Bordetella pertussis, remains a major global health problem. Each year around 40 million of pertussis cases resulting in 200,000-400,000 annual deaths occur worldwide. Pertussis toxin is a major virulence factor of B.

Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: insights into the genes required for mouse infectivity.

The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by exceedingly low transformation rates in low-passage, infectious organisms. Using the infectious, moderately transformable B. burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1 transposon vector pGKT, we have constructed a defined transposon library for the efficient genome-wide investigation of genes required for wild-type pathogenesis, in vitro growth, physiology, morphology, and plasmid replication.

The ins and outs of pertussis toxin.

Pertussis toxin, produced and secreted by the whooping cough agent Bordetella pertussis, is one of the most complex soluble bacterial proteins. It is actively secreted through the B. pertussis cell envelope by the Ptl secretion system, a member of the widespread type IV secretion systems.

Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection.

Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion.

NMR structure of a complex between the VirB9/VirB7 interaction domains of the pKM101 type IV secretion system.

Type IV secretion (T4S) systems translocate DNA and protein effectors through the double membrane of Gram-negative bacteria. The paradigmatic T4S system in Agrobacterium tumefaciens is assembled from 11 VirB subunits and VirD4. Two subunits, VirB9 and VirB7, form an important stabilizing complex in the outer membrane.

Protein secretion through autotransporter and two-partner pathways.

Two distinct protein secretion pathways, the autotransporter (AT) and the two-partner secretion (TPS) pathways are characterized by their apparent simplicity. Both are devoted to the translocation across the outer membrane of mostly large proteins or protein domains. As implied by their name, AT proteins contain their own transporter domain, covalently attached to the C-terminal extremity of the secreted passenger domain, while TPS systems are composed of two separate proteins, with TpsA being the secreted protein and TpsB its specific transporter.

Surface anchoring of bacterial subtilisin important for maturation function.

Many extracytoplasmic proteins undergo proteolytic processing during secretion, which is essential to their maturation. These post-translational modifications are carried out by specific enzymes whose subcellular localization is important for function. We have described a maturation subtilisin in Gram-negative Bordetella pertussis, the autotransporter SphB1.

Role of adhesin release for mucosal colonization by a bacterial pathogen.

Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied.