Accumulation of avirulent Bordetella pertussis Bvg mutants in the course of experimental whooping cough in mice

Medkova, A. Yu.; Sinyashina, L. N.; Rumyantseva, Yu. P.; Voronina, Olga L.; Kunda, Marina S.; Karataev, G. I.

doi:10.3103/s0891416813040058

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…The persistence of the JN1 mutant further indicates that downregulation of production of the known virulence factors may allow B. pertussis low-level colonization of the airway mucosa without harnessing the inflammatory and immune responses of the host. This would go well with the intriguing observation that persistent infection of the airways of primates was accompanied by accumulation of Bvg 2 phase-locked B. pertussis mutants (37,38). Moreover, B. pertussis antigen was detected inside columnar epithelial cells of the bronchiole and trachea of an infant 8 weeks after a diagnosis of pertussis (69).…”

Section: Discussionsupporting

confidence: 61%

“…At temperatures occurring in the nasal cavity and nasopharynx of humans (;32 to 34°C), the bacteria might adopt an intermediary Bvg i phase, reducing expression of some virulence factors and upregulating production of some proteins involved in biofilm formation, such as BipA (29,35,36). Moreover, an intriguing observation was made during long-term follow-up of B. pertussis-infected mice and primates, where B. pertussis persistence in the nasopharynx and accumulation of Bvg 2 phase-locked mutants was observed over several months after infection (37,38). Downregulation of expression of most virulence factors was also recently observed in the course of B. pertussis adaptation to an intracellular niche within human THP-1 macrophages (39).…”

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confidence: 99%

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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

et al. 2020

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We show that a spontaneous mutation that upregulates transcription of an operon encoding ribosomal proteins and causes overproduction of the downstream-encoded α subunit (RpoA) of RNA polymerase causes global effects on gene expression levels and proteome composition of Bordetella pertussis. Nevertheless, the resulting important downregulation of the BvgAS-controlled expression of virulence factors of the whooping cough agent did not compromise its capacity to persist for prolonged periods inside primary human macrophage cells, and it even enhanced its capacity to persist in infected mouse lungs.

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Section: Discussionsupporting

confidence: 61%

mentioning

confidence: 99%

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

et al. 2020

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“…pertussis expresses Bvg(−) genes, including those from the flagellar operon (9), and Bvg(−) B. pertussis strains have been isolated from patients during infection (10). In addition, flagellar expression and motility appear to be important for virulence phenotypes.…”

Section: Observationmentioning

confidence: 99%

“…These data do not address the relevance of flagellar expression or motility for virulence and pathogenicity, due to these phenotypes occurring in the Bvg(−) phase. However, Karataev et al and Medkova et al have shown recently that Bvg(−) organisms are present in the upper respiratory tracts of infected humans and mice (10, 25). Furthermore, expression of flagellar genes has been demonstrated in vivo in mice.…”

Section: Observationmentioning

confidence: 99%

Bordetella pertussis Can Be Motile and Express Flagellum-Like Structures

Hoffman

Gonyar

Zacca

et al. 2019

mBio

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Bordetella bronchiseptica encodes and expresses a flagellar apparatus. In contrast, Bordetella pertussis, the causative agent of whooping cough, has historically been described as a nonmotile and nonflagellated organism. The previous statements that B. pertussis was a nonmotile organism were consistent with a stop codon located in the flagellar biosynthesis gene, flhA, discovered when the B. pertussis Tohama I genome was sequenced and analyzed by Parkhill et al. in 2003 (J. Parkhill, M. Sebaihia, A. Preston, L. D. Murphy, et al., Nat Genet, 35:32–40, 2003, https://doi.org/10.1038/ng1227). The stop codon has subsequently been found in all annotated genomes. Parkhill et al. also showed, however, that B. pertussis contains all genetic material required for flagellar synthesis and function. We and others have determined by various transcriptomic analyses that these flagellar genes are differentially regulated under a variety of B. pertussis growth conditions. In light of these data, we tested for B. pertussis motility and found that both laboratory-adapted strains and clinical isolates can be motile. Upon isolation of motile B. pertussis, we discovered flagellum-like structures on the surface of the bacteria. B. pertussis motility appears to occur primarily in the Bvg(−) phase, consistent with regulation present in B. bronchiseptica. Motility can also be induced by the presence of fetal bovine serum. These observations demonstrate that B. pertussis can express flagellum-like structures, and although it remains to be determined if B. pertussis expresses flagella during infection or if motility and/or flagella play roles during the cycle of infection and transmission, it is clear that these data warrant further investigation. IMPORTANCE This report provides evidence for motility and expression of flagella by B. pertussis, a bacterium that has been reported as nonmotile since it was first isolated and studied. As with B. bronchiseptica, B. pertussis cells can express and assemble a flagellum-like structure on their surface, which in other organisms has been implicated in several important processes that occur in vivo. The discovery that B. pertussis is motile raises many questions, including those regarding the mechanisms of regulation for flagellar gene and protein expression and, importantly, the role of flagella during infection. This novel observation provides a foundation for further study of Bordetella flagella and motility in the contexts of infection and transmission.

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“…although recent studies have shown that this may not be the only case; Bvg(-) mutants have recently been isolated from patients infected with B. pertussis (29,74,75). Bvg(-) bacteria are hardier and survive on abiotic surfaces for longer periods of time, and also grow at a faster rate, likely due to major differences in gene expression associated with metabolism and nutrient uptake (Figure 1.4) (54,64).…”

Section: Phase Variationmentioning

confidence: 99%

The "Mystery Phases": Bordetella Adenylate Cyclase Toxin and biofilm in the Bvg-Intermediate Phase & Bordetella pertussis Motility and Flagella in the Bvg-Minus Phase

Hoffman¹

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Bordetella pertussis is the Gram-negative bacterial pathogen responsible for the life-threatening disease, whooping cough (pertussis). The bacterium has been of increasing interest in the research community due to the reemergence of this vaccine-preventable disease. In fact, the numbers of pertussis cases reported to the CDC annually are similar to those reported prior to the introduction of the whole cell pertussis vaccine. The increased number of cases coincides with the transition to the acellular vaccine, comprised of just one to five B. pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae 2 and fimbriae 3). This correlation, while not the only contributing factor to reemergence of the disease, highlights the fact that not enough was known about the biology of B. pertussis before the acellular vaccine was created. In fact, it has only recently been shown that B. pertussis forms biofilm during infection, and that biofilm may be a virulence trait of Bordetella. These biofilms form both in vitro on abiotic surfaces and in vivo in the mouse trachea and nasopharynx.Biofilms are defined as surface-associated bacterial growth, in which the bacteria are covered in extracellular polymeric substance (EPS or matrix), comprised of polysaccharides, eDNA, and proteins. These microbial communities are often associated with persistent infections and in some cases, asymptomatic infections.The mechanisms by which biofilm formation occurs and are regulated are not completely understood in the Bordetella species, although several pathways and important components of the biofilm have been identified. One of the major observations that inspired this work was that a B. bronchiseptica strain from III which the cyaA gene, encoding adenylate cyclase toxin (ACT), has been deleted, formed more biofilm than wild type bacteria, suggesting the possibility of an inhibitory effect of ACT. ACT is a host-directed, protein, bacterial toxin, and the toxin's role as an inhibitor of biofilm is unprecedented. It was also discovered by Zaretzky et al that ACT binds Filamentous Hemagglutinin (FHA), a surface displayed adhesin required for biofilm formation. Until now, the consequences of this interaction were unknown. We have found that ACT binds to FHA via a direct interaction between the catalytic domain of ACT (AC domain) and the mature cterminal domain of FHA (MCD). This protein-protein interaction results in the inhibition and disruption of biofilm formation. The AC domain is also able to inhibit biofilm of other bacterial species that express an FHA-like protein.In fitting these findings into the overall body of knowledge regarding Bordetellae biofilm, we found major differences in the regulatory processes controlling B. bronchiseptica and B. pertussis biofilm. Flagella are essential for initial binding and mature biofilm formation by B. bronchiseptica. In contrast, B. pertussis forms biofilm despite being classically defined as a non-motile and nonflagellated bacterium. B. pertussis encodes all of the required ge...

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Accumulation of avirulent Bordetella pertussis Bvg mutants in the course of experimental whooping cough in mice

Cited by 10 publications

References 14 publications

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

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

Bordetella pertussis Can Be Motile and Express Flagellum-Like Structures

The "Mystery Phases": Bordetella Adenylate Cyclase Toxin and biofilm in the Bvg-Intermediate Phase & Bordetella pertussis Motility and Flagella in the Bvg-Minus Phase

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