Avirulent phenotype promotes
            <i>Bordetella pertussis</i>
            adaptation to the intramacrophage environment

Farman, Mariam R.; Petráčková, Denisa; Kumar, Dilip; Držmíšek, Jakub; Saha, Argha; Čurnová, Ivana; Čapek, Jan; Hejnarová, Václava; Amman, Fabian; Hofacker, Ivo L.; Večerek, Branislav

doi:10.1080/22221751.2022.2146536

Cited by 4 publications

(10 citation statements)

References 88 publications

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“…Indeed, it has been demonstrated that whereas Cya and Ptx are involved in manipulating the macrophage response, promoting bacterial intracellular survival, 12 the avirulent phase is also involved in the adaptation of the bacterium to the intramacrophage environment. 11 Our results might indicate that BP1092 does not shut down the Bvg-regulon but fine-tunes it to strike an appropriate balance between its beneficial effects in immune evasion and the cytotoxic effects of toxins that may induce the death of the infected cell.…”

Section: ■ Discussionmentioning

confidence: 87%

“…B. pertussis undergoes extensive gene expression modulation during intracellular infection, with many genes involved belonging to the BvgAS regulon. , However, it has been suggested that other alternative regulatory systems may also contribute to the adaptation to the intracellular environment . BP1092 is a putative TCS histidine kinase that exhibits significantly increased levels upon bacterial internalization by a human macrophage cell line.…”

Section: Resultsmentioning

confidence: 99%

“…However, a recent study suggested that this phase might be induced during the adaptation of B. pertussis to the intramacrophage environment. 11 To evaluate the role of BP1092 in protein production under modulating conditions, we compared the protein levels in B. pertussis ΔBP1092 and the wt strain grown in the presence of 50 mM MgSO 4 . The levels of four proteins significantly changed in the mutant strain compared to the wt strain, whereas eight proteins showed a trend in regulation (Table 2).…”

Section: Changes In Protein Levels Caused By Bp1092 Deletion Under Mo...mentioning

confidence: 99%

“…pertussis during the infection of human macrophages revealed that intracellular bacteria undergo a shift from a virulent (Bvg+) to an avirulent (Bvg-) phenotype. This transition seems to benefit the survival and persistence of the bacteria within macrophages . However, it has been demonstrated that internalized B.…”

Section: Introductionmentioning

confidence: 99%

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Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival

Debandi,

Carrica,

Hentschker

et al. 2024

J. Proteome Res.

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Bordetella pertussis persists inside host cells, and virulence factors are crucial for intracellular adaptation. The regulation of B. pertussis virulence factor transcription primarily occurs through the modulation of the two-component system (TCS) known as BvgAS. However, additional regulatory systems have emerged as potential contributors to virulence regulation. Here, we investigate the impact of BP1092, a putative TCS histidine kinase that shows increased levels after bacterial internalization by macrophages, on B. pertussis proteome adaptation under nonmodulating (Bvg+) and modulating (Bvg−) conditions. Using mass spectrometry, we compare B. pertussis wild-type (wt), a BP1092-deficient mutant (ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance of 10 proteins, including five virulence factors. Specifically, under nonmodulating conditions, the mutant strain showed decreased levels of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating conditions, the mutant strain exhibited reduced levels of BvgA and BvgS compared to those of the wt. Functional assays further revealed that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together, our findings allow us to propose BP1092 as a novel player involved in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment. The data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD041940.

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Section: ■ Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Changes In Protein Levels Caused By Bp1092 Deletion Under Mo...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival

Debandi,

Carrica,

Hentschker

et al. 2024

J. Proteome Res.

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“…For example, we recently reported that B. bronchiseptica mutant strains deficient in adenylate cyclase toxin, dermonecrotic toxin, or the type III secretion system colonized rat tracheas and lungs similar to a wild‐type strain, 3 implying the existence of unknown additional virulence factors or redundant roles of known virulence factors. Several studies also pointed out that the bacteria express Bvg – phase‐dependent factors in host cells and animals, 4–6 but the roles of these factors in the infection process are not elaborated. Therefore, in this study, to seek novel factors involved in the Bordetella pathogenicity, we conducted a genome‐wide screening for genes that support colonization/infection of B. bronchiseptica using a transposon sequencing technique (Tn‐seq), which combines large‐scale transposon mutagenesis with next‐generation sequencing 7 .…”

Section: Introductionmentioning

confidence: 99%

RpoN (sigma factor 54) contributes to bacterial fitness during tracheal colonization of Bordetella bronchiseptica

Ma,

Nugraha,

Hiramatsu

et al. 2023

Microbiology and Immunology

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The Gram‐negative pathogenic bacterium Bordetella bronchiseptica is a respiratory pathogen closely related to Bordetella pertussis, the causative agent of whooping cough. Despite sharing homologous virulence factors, B. bronchiseptica infects a broad range of mammalian hosts, including some experimental animals, whereas B. pertussis is strictly adapted to humans. Therefore, B. bronchiseptica is often used as a representative model to explore the pathogenicity of Bordetella in infection experiments with laboratory animals. Although Bordetella virulence factors, including toxins and adhesins have been studied well, our recent study implied that unknown virulence factors are involved in tracheal colonization and infection. Here, we investigated bacterial genes contributing to tracheal colonization by high‐throughput transposon sequencing (Tn‐seq). After the screening, we picked up 151 candidate genes of various functions and found that a rpoN‐deficient mutant strain was defective in tracheal colonization when co‐inoculated with the wild‐type strain. rpoN encodes σ54, a sigma factor that regulates the transcription of various genes, implying its contribution to various bacterial activities. In fact, we found RpoN of B. bronchiseptica is involved in bacterial motility and initial biofilm formation. From these results, we propose that RpoN supports bacterial colonization by regulating various bacteriological functions.

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T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis

Držmíšek,

Petráčková,

Dienstbier

et al. 2023

Emerging Microbes & Infections

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Bordetella pertussis is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, B. pertussis produces the type III secretion system, but its role in the pathogenesis of B. pertussis is enigmatic and yet to be elucidated. Here, we combined RNA-seq, LC-MS/MS, and co-immunoprecipitation techniques to identify and characterize the novel CesT family T3SS chaperone BP2265. We show that this chaperone specifically interacts with the secreted T3SS regulator BtrA and represents the first non-flagellar chaperone required for the secretion of an anti-sigma factor. In its absence, secretion but not production of BtrA and most T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS extends beyond its activity as an antagonist of the sigma factor BtrS. Predictions made by artificial intelligence system AlphaFold support the chaperone function of BP2265 towards BtrA and outline the structural basis for the interaction of BtrA with its target BtrS. We propose to rename BP2265 to BtcB for the Bordetella type III chaperone of BtrA. In addition, the absence of the BtcB chaperone results in increased expression of numerous flagellar genes and several virulence genes. While increased production of flagellar proteins and intimin BipA translated into increased biofilm formation by the mutant, enhanced production of virulence factors resulted in increased cytotoxicity towards human macrophages. We hypothesize that these phenotypic traits result indirectly from impaired secretion of BtrA and altered activity of the BtrA/BtrS regulatory node.

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Avirulent phenotype promotes Bordetella pertussis adaptation to the intramacrophage environment

Cited by 4 publications

References 88 publications

Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival

Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival

RpoN (sigma factor 54) contributes to bacterial fitness during tracheal colonization of Bordetella bronchiseptica

T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis

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