Zoonotic Transmission of Vaccine-Derived Bordetella bronchiseptica
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PROVIDER: S-EPMC10466264 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:Transmission of pathogens has been notoriously difficult to study under laboratory conditions leaving knowledge gaps regarding how bacterial factors and host immune components affect the spread of infections between hosts. We describe the development of a mouse model of transmission of a natural pathogen, Bordetella bronchiseptica, and its use to assess the impact of host immune functions. Although B. bronchiseptica transmits poorly between wild-type mice and mice lacking other immune components, it transmits efficiently between mice deficient in Toll-Like Receptor 4 (TLR4). TLR4-mutant mice were more susceptible to initial colonization, and poorly controlled pathogen growth and shedding. Heavy neutrophil infiltration distinguished TLR4-deficient responses, and neutrophil depletion did not affect respiratory CFU load, but decreased bacterial shedding. The effect of TLR4 response on transmission may explain the extensive variation in TLR4 agonist potency observed among closely related subspecies of Bordetella. This transmission model will enable mechanistic studies of how pathogens spread from one host to another, the defining feature of infectious disease.
| S-EPMC3907416 | biostudies-literature
Project description:Whooping cough is resurging in the United States despite high vaccine coverage. The rapid rise of Bordetella pertussis isolates lacking pertactin (PRN), a key vaccine antigen, has led to concerns about vaccine-driven evolution. Previous studies showed that pertactin can mediate binding to mammalian cells in vitro and act as an immunomodulatory factor in resisting neutrophil-mediated clearance. To further investigate the role of PRN in vivo, we examined the functions of pertactin in the context of a more naturally low dose inoculation experimental system using C3H/HeJ mice that is more sensitive to effects on colonization, growth and spread within the respiratory tract, as well as an experimental approach to measure shedding and transmission between hosts. A B. bronchiseptica pertactin deletion mutant was found to behave similarly to its wild-type (WT) parental strain in colonization of the nasal cavity, trachea, and lungs of mice. However, the pertactin-deficient strain was shed from the nares of mice in much lower numbers, resulting in a significantly lower rate of transmission between hosts. Histological examination of respiratory epithelia revealed that pertactin-deficient bacteria induced substantially less inflammation and mucus accumulation than the WT strain and in vitro assays verified the effect of PRN on the induction of TNF-α by murine macrophages. Interestingly, only WT B. bronchiseptica could be recovered from the spleen of infected mice and were further observed to be intracellular among isolated splenocytes, indicating that pertactin contributes to systemic dissemination involving intracellular survival. These results suggest that pertactin can mediate interactions with immune cells and augments inflammation that contributes to bacterial shedding and transmission between hosts. Understanding the relative contributions of various factors to inflammation, mucus production, shedding and transmission will guide novel strategies to interfere with the reemergence of pertussis.
| S-EPMC8336816 | biostudies-literature
Project description:BackgroundThe lack of animal models to experimentally study how infectious agents transmit between hosts limits our understanding of what makes some pathogens so contagious.MethodsWe recently developed a Bordetella bronchiseptica mouse model to study transmission and have used it to assess, for the first time, which of several well-studied "virulence factors" common to classical Bordetella species contribute to transmission.ResultsAmong 13 mutants screened, a mutant lacking an extracellular polysaccharide (EPS) locus consistently failed to transmit. The loss of EPS had no obvious effect on in vitro characteristics of growth, adherence, cytotoxicity, or serum resistance, though it profoundly reduced the ability of the mutant to colonize the lower respiratory tract of mice. While wild-type B. bronchiseptica was shed from colonized mice and efficiently transmitted to cage-mates, the mutant colonized less efficiently, shed at lower numbers, and consequently did not transmit to naive animals.ConclusionsThese results have important implications for potential roles of polysaccharides in the pathogenesis and transmission of Bordetella species as well as other respiratory pathogens. Cases of pertussis (whooping cough) caused by Bordetella pertussis are on the rise, and understanding factors that contribute to their spread is critical to its control.
| S-EPMC5853889 | biostudies-literature
Project description:Bordetella bronchiseptica is a zoonotic respiratory pathogen commonly found in domesticated farm and companion animals, including dogs and cats. Here, we report isolation of B. bronchiseptica from a sputum sample of a cystic fibrosis patient recently exposed to a kitten with an acute respiratory illness. Genetic characterization of the isolate and comparison with other isolates of human or feline origin strongly suggest that the kitten was the source of infection.
| S-EPMC3323701 | biostudies-literature
Project description:Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica--a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans--within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter), or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings--as opposed to, for example, breeder or maternal cohorts--as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control.
| S-EPMC3002977 | biostudies-literature
Project description:Copper is both essential and toxic to living beings, which therefore tightly control its intracellular concentration. At the host-pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in the whooping cough agent Bordetella pertussis, which lives in the human respiratory mucosa and has no environmental reservoir. B. pertussis has considerably streamlined copper homeostasis mechanisms relative to other Gram-negative bacteria. Its single remaining defense line against copper intoxication consists in a metallochaperone diverted for copper passivation and two enzymes involved in peroxide detoxification, which together fight two stresses encountered in phagolysosomes. The three proteins are encoded by an original, composite operon assembled in an environmental ancestor and which is under sensitive control by copper. Interestingly, this system appears to play a role in persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a new strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.
2020-10-27 | GSE145049 | GEO
Project description:Multiple lines of evidence suggest that Bordetella species have a significant life stage outside of the mammalian respiratory tract that has yet to be defined. The Bordetella virulence gene (BvgAS) two-component system, a paradigm for a global virulence regulon, controls the expression of many "virulence factors" expressed in the Bvg positive (Bvg+) phase that are necessary for successful respiratory tract infection. A similarly large set of highly conserved genes are expressed under Bvg negative (Bvg-) phase growth conditions; however, these appear to be primarily expressed outside of the host and are thus hypothesized to be important in an undefined extrahost reservoir. Here, we show that Bvg- phase genes are involved in the ability of Bordetella bronchiseptica to grow and disseminate via the complex life cycle of the amoeba Dictyostelium discoideum. Unlike bacteria that serve as an amoeba food source, B. bronchiseptica evades amoeba predation, survives within the amoeba for extended periods of time, incorporates itself into the amoeba sori, and disseminates along with the amoeba. Remarkably, B. bronchiseptica continues to be transferred with the amoeba for months, through multiple life cycles of amoebae grown on the lawns of other bacteria, thus demonstrating a stable relationship that allows B. bronchiseptica to expand and disperse geographically via the D. discoideum life cycle. Furthermore, B. bronchiseptica within the sori can efficiently infect mice, indicating that amoebae may represent an environmental vector within which pathogenic bordetellae expand and disseminate to encounter new mammalian hosts. These data identify amoebae as potential environmental reservoirs as well as amplifying and disseminating vectors for B. bronchiseptica and reveal an important role for the Bvg- phase in these interactions.
| S-EPMC5389573 | biostudies-literature
Project description:Pertactin is an outer membrane protein expressed by Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica that induces protective immunity to Bordetella infections. The immunodominant and immunoprotective epitopes of pertactin include two repeated regions, I and II. Comparison of these two repeated regions showed that B. parapertussis pertactin is invariant, whereas B. pertussis pertactin varies mostly in region I and B. bronchiseptica pertactin varies in both repeated regions I and II, but mostly in region II. These differences may result from specific characteristics of these Bordetella species.
| S-EPMC98445 | biostudies-literature
Project description:The respiratory pathogenic bacterium Bordetella bronchiseptica can persistently survive in terrestrial and aquatic environments, providing a source of infection. However, the environmental lifestyle of the bacterium is poorly understood. In this study, expecting repeated encounters of the bacteria with environmental protists, we explored the interaction between B. bronchiseptica and a representative environmental amoeba, Acanthamoeba castellanii, and found that the bacteria resisted amoeba digestion and entered contractile vacuoles (CVs), which are intracellular compartments involved in osmoregulation, to escape amoeba cells. In prolonged coculture, A. castellanii supported the proliferation of B. bronchiseptica. The avirulent Bvg- phase, but not the virulent Bvg+ phase, of the bacteria was advantageous for survival in the amoebae. We further demonstrate that two Bvg+ phase-specific virulence factors, filamentous hemagglutinin and fimbriae, were targeted for predation by A. castellanii. These results are evidence that the BvgAS two-component system, the master regulator for Bvg phase conversion, plays an indispensable role in the survival of B. bronchiseptica in amoebae. IMPORTANCE The pathogenic bacterium Bordetella bronchiseptica, which causes respiratory diseases in various mammals, exhibits distinct Bvg+ and Bvg- phenotypes. The former represents the virulent phase, in which the bacteria express a set of virulence factors, while the role of the latter in the bacterial life cycle remains to be understood. In this study, we demonstrate that B. bronchiseptica in the Bvg- phase, but not the Bvg+ phase, survives and proliferates in coculture with Acanthamoeba castellanii, an environmental amoeba. Two Bvg+ phase-specific virulence factors, filamentous hemagglutinin and fimbriae, were targeted by A. castellanii predation. B. bronchiseptica turns into the Bvg- phase at temperatures in which the bacteria normally encounter these amoebae. These findings demonstrate that the Bvg- phase of B. bronchiseptica is advantageous for survival outside mammalian hosts and that the bacteria can utilize protists as transient hosts in natural environments.
| S-EPMC10100856 | biostudies-literature
Project description:Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity.
| S-EPMC3054038 | biostudies-literature