A Mutation Upstream of the
            <i>rplN-rpsD</i>
            Ribosomal Operon Downregulates Bordetella pertussis Virulence Factor Production without Compromising Bacterial Survival within Human Macrophages

Novák, Jakub; Jurnečka, David; Linhartová, Irena; Holubová, Jana; Staněk, Ondřej; Štipl, Daniel; Dienstbier, Ana; Večerek, Branislav; Azevedo, Nayara; Provazník, Jan; Beneš, Vladimı́r; Šebo, Peter

doi:10.1128/msystems.00612-20

Cited by 5 publications

(4 citation statements)

References 91 publications

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“…The location of the pathogen in these reservoirs is still under investigation. Bordetella pertussis was historically considered as an extracellular pathogen, but pr e vious studies fr om our gr oup and others have shown that this bacterium might be an intracellular facultative pathogen (Hellwig et al 1999, Lamberti et al 2008, Jakub et al 2020, Petrá čková et al 2020. We showed that B. pertussis can survive inside immune cells, such as neutrophils and macr opha ges, and within pha gosomes that do not fuse with lysosomes (Lamberti et al 2008(Lamberti et al , 2010.…”

Section: Introductionmentioning

confidence: 60%

Bordetella pertussis targets the basolateral membrane of polarized respiratory epithelial cells, gets internalized, and survives in intracellular locations

Baroli,

Gorgojo,

Blancá

et al. 2023

Pathogens and Disease

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The airway epithelial barrier is a continuous highly organized cell layer that separates the exterior from the underlying mucosal tissue, preventing pathogen invasion. Several respiratory pathogens have evolved mechanisms to compromise this barrier, invade and even reside alive within the epithelium. Bordetella pertussis is a persistent pathogen that infects the human airway epithelium, causing whooping cough. Previous studies have shown that B. pertussis survives inside phagocytic and nonphagocytic cells, suggesting that there might be an intracellular stage involved in the bacterial infectious process and/or in the pathogen persistence inside the host. In this study we found evidence that B. pertussis is able to survive inside respiratory epithelial cells. According to our results, this pathogen preferentially attaches near or on top of the tight junctions in polarized human bronchial epithelial cells and disrupts these structures in an adenylate cyclase-dependent manner, exposing their basolateral membrane. We further found that the bacterial internalization is significantly higher in cells exposing this membrane compared with cells only exposing the apical membrane. Once internalized, B. pertussis mainly remains in nondegradative phagosomes with access to nutrients. Taken together, these results point at the respiratory epithelial cells as a potential niche of persistence.

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Section: Introductionmentioning

confidence: 60%

Bordetella pertussis targets the basolateral membrane of polarized respiratory epithelial cells, gets internalized, and survives in intracellular locations

Baroli,

Gorgojo,

Blancá

et al. 2023

Pathogens and Disease

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“…Another artefact is confirmed by running the software without strand bias correction, where the number of unmapped tracts increases without an improvement on the number of mapped reads (result not shown). The exception is sample ERR4176311, a B. pertussis Tohama I delta-BP3063 mutant from ( 24 ), where almost all tracts are seen in only one strand: the 139 348 tracts mapped to the reference decrease to only 875 once we remove tracts not seen on both strand directions. This sample was removed from subsequent analyses.…”

Section: Resultsmentioning

confidence: 99%

Tatajuba: exploring the distribution of homopolymer tracts

Martins

Bloomfield

Stoakes

et al. 2022

NAR Genomics and Bioinformatics

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Length variation of homopolymeric tracts, which induces phase variation, is known to regulate gene expression leading to phenotypic variation in a wide range of bacterial species. There is no specialized bioinformatics software which can, at scale, exhaustively explore and describe these features from sequencing data. Identifying these is non-trivial as sequencing and bioinformatics methods are prone to introducing artefacts when presented with homopolymeric tracts due to the decreased base diversity. We present tatajuba, which can automatically identify potential homopolymeric tracts and help predict their putative phenotypic impact, allowing for rapid investigation. We use it to detect all tracts in two separate datasets, one of Campylobacter jejuni and one of three Bordetella species, and to highlight those tracts that are polymorphic across samples. With this we confirm homopolymer tract variation with phenotypic impact found in previous studies and additionally find many more with potential variability. The software is written in C and is available under the open source licence GNU GPLv3.

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“…Macrophages represent a very heterogenous and specialized group of cells ( 35 ) and the difference observed between the two studies could be related to the distinct features of AMs compared to monocyte- or bone marrow-derived macrophages ( 36 , 37 ). Interestingly, a recent study suggested that B. pertussis may survive in a dormant, non-culturable state, for a longer time inside macrophages ( 38 ). This observation opens a new axis that will have to be further explored in order to understand the intracellular fate of B. pertussis inside alveolar macrophages, which have been described as potential infectious reservoir, in particular because of their long lifespan ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Combined regulation of pro-inflammatory cytokines production by STAT3 and STAT5 in a model of B. pertussis infection of alveolar macrophages

Khiter,

Kherrouche,

Dubois

et al. 2023

Front. Immunol.

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Bordetella pertussis is a highly contagious respiratory pathogen responsible for whooping-cough or pertussis. Despite high vaccination coverage worldwide, this gram-negative bacterium continues to spread among the population. B. pertussis is transmitted by aerosol droplets from an infected individual to a new host and will colonize its upper respiratory tract. Alveolar macrophages (AMs) are effector cells of the innate immune system that phagocytose B. pertussis and secrete both pro-inflammatory and antimicrobial mediators in the lungs. However, understanding their role in B. pertussis pathogenesis at the molecular level is hampered by the limited number of primary AMs that can be collected in vivo. In order to decipher the regulation of innate response induced by B. pertussis infection, we used for the first time self-renewing, non-transformed cells, called Max Planck Institute (MPI) cells, which are phenotypically and functionally very close to pulmonary AMs. Using optimized infection conditions, we characterized the entry and the clearance of B. pertussis within MPI macrophages. We showed that under these conditions, MPI cells exhibit a pro-inflammatory phenotype with the production of TNF, IL-1β, IL-6 and MIP-2α, similarly to primary AMs purified from broncho-alveolar fluids of mice. In addition, we explored the yet uncharacterized role of the signal transduction activator of transcription (STAT) proteins family in the innate immune response to B. pertussis infection and showed for the first time the parallel regulation of pro-inflammatory cytokines by STAT3 and STAT5 in MPI macrophages infected by B. pertussis. Altogether, this work highlights the interest of using MPI cells for experiments optimization and preliminary data acquisition to understand B. pertussis interaction with AMs, and thus significantly reduce the number of animals to be sacrificed.

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A Mutation Upstream of the rplN-rpsD Ribosomal Operon Downregulates Bordetella pertussis Virulence Factor Production without Compromising Bacterial Survival within Human Macrophages

Cited by 5 publications

References 91 publications

Bordetella pertussis targets the basolateral membrane of polarized respiratory epithelial cells, gets internalized, and survives in intracellular locations

Bordetella pertussis targets the basolateral membrane of polarized respiratory epithelial cells, gets internalized, and survives in intracellular locations

Tatajuba: exploring the distribution of homopolymer tracts

Combined regulation of pro-inflammatory cytokines production by STAT3 and STAT5 in a model of B. pertussis infection of alveolar macrophages

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