Filamentous Hemagglutinin of
            <i>Bordetella Pertussis</i>
            : a Key Adhesin with Immunomodulatory Properties?

Romero, Rodrigo Villarino; Osička, Radim; Šebo, Peter

doi:10.2217/fmb.14.77

Cited by 26 publications

(19 citation statements)

References 150 publications

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“…There is both direct and indirect evidence for in vivo expression of the T3SS in B. pertussis. For example, Bsp22 was detected in lung homogenate of B. pertussis-infected mouse (7,44,45). In addition, some clinical isolates that did not produce BteA (one of the effectors of the T3SS) due to an insertion sequence (IS) in the promoter of bteA still secreted BopD and produced a functional T3SS apparatus (21).…”

Section: Discussionmentioning

confidence: 99%

Glutamate Limitation, BvgAS Activation, and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System

et al. 2016

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Bordetella pertussis is a bacterium that is considered to be highly adapted to humans, and it has not been isolated from the environment. As this bacterium does not utilize sugars, the abundant supply of glutamate in Stainer Scholte (SS) medium enables B. pertussis to grow efficiently in liquid culture in vitro, and as such, SS medium is a popular choice for laboratory experiments. However, the concentration of glutamate in the in vivo niche of B. pertussis is quite low. We investigated the bacterial response to low concentrations of glutamate to elucidate bacterial physiology via the expression of the type 3 secretion system (T3SS), and we discuss its relationship to the Bvg mode in which the two-component regulator of pathogenesis (BvgAS) is activated. Glutamate limitation induced the expression of both the T3SS apparatus and effector genes at the transcriptional level. (p)ppGpp, a modulator of the stringent response, was necessary for maximum expression of the T3SS genes. These observations indicate that the expression of the T3SS is managed by nutrient starvation. In addition, the autoaggregation ability was high in the absence of glutamate and no autoaggregation was observed in glutamate-replete medium. Taken together, glutamate-limited conditions in Bvg ؉ mode elicit the high expression of T3SS genes in B. pertussis and promotes its sessile form. IMPORTANCEBordetella pertussis is a highly contagious pathogen that causes respiratory infectious disease. In spite of the increasing use of vaccination, the number of patients with pertussis is increasing. The proteins produced in vivo often are different from the protein profile under laboratory conditions; therefore, the development of conditions reflecting the host environment is important to understand native bacterial behavior. In the present study, we examined the effect of glutamate limitation, as its concentration in vivo is much lower than that in the culture medium currently used for B. pertussis experiments. As predicted, the T3SS was induced by glutamate limitation. These results are suggestive of the importance of regulation by nutrient conditions and in the pathogenicity of B. pertussis.

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Section: Discussionmentioning

confidence: 99%

Glutamate Limitation, BvgAS Activation, and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System

et al. 2016

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“…Filamentous hemagglutinin as a key virulence factor has been reported in both plant and animal pathogens including E. chrysanthemi, B. pertussis , and A. baumannii (Rojas et al, 2002; Astaneh et al, 2014; Romero et al, 2014). In our study, we found that compared to the wild type, TSS fha exhibited a distinct reduction in serum survival, which is the first observation of an association between bacterial FHA and serum resistance.…”

Section: Discussionmentioning

confidence: 99%

“…It is secreted in a Sec-dependent manner by the two-partner secretion (TPS) system, which includes an outer membrane-associated accessory protein interacting with FHA N-proximal secretion domain. Functionally, it has proapoptotic activity and promotes bacterial aggregation (Locht et al, 1993, 2001; Romero et al, 2014). In Xanthomonas axonopodis pv.…”

Section: Introductionmentioning

confidence: 99%

“…Another FHA-like protein in Acinetobacter baumannii plays a role in virulence in a mouse lethal model of infection, promoting biofilm formation and mediating the adhesion of A. baumannii to epithelial cells (Astaneh et al, 2014). Apart from its role as an adhesin, FHA of B. pertussis and Bordetella bronchiseptica also possesses immunomodulatory properties which may contribute to subversion of host innate and adaptive immunity (Abramson et al, 2001; Braat et al, 2007; Julio et al, 2009; Henderson et al, 2012; Romero et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Pseudomonas fluorescens Filamentous Hemagglutinin, an Iron-Regulated Protein, Is an Important Virulence Factor that Modulates Bacterial Pathogenicity

Sun¹,

Chi

Sun

2016

Front. Microbiol.

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Pseudomonas fluorescens is a common bacterial pathogen to a wide range of aquaculture animals including various species of fish. In this study, we employed proteomic analysis and identified filamentous hemagglutinin (FHA) as an iron-responsive protein secreted by TSS, a pathogenic P. fluorescens isolate. In vitro study showed that compared to the wild type, the fha mutant TSSfha (i) exhibited a largely similar vegetative growth profile but significantly retarded in the ability of biofilm growth and producing extracellular matrix, (ii) displayed no apparent flagella and motility, (iii) was defective in the attachment to host cells and unable to form self-aggregation, (iv) displayed markedly reduced capacity of hemagglutination and surviving in host serum. In vivo infection analysis revealed that TSSfha was significantly attenuated in the ability of dissemination in fish tissues and inducing host mortality, and that antibody blocking of the natural FHA produced by the wild type TSS impaired the infectivity of the pathogen. Furthermore, when introduced into turbot as a subunit vaccine, recombinant FHA elicited a significant protection against lethal TSS challenge. Taken together, these results indicate for the first time that P. fluorescens FHA is a key virulence factor essential to multiple biological processes associated with pathogenicity.

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“…Fha also appears to act as a suppressor of inflammation in the airways [19,20]. As Fha is a component of acellular pertussis vaccines, this immunomodulatory activity may be a problem for the efficacy of these vaccines.…”

Section: Role and Activity Of B Pertussis Virulence Factorsmentioning

confidence: 99%

Bordetella pertussis

Carbonetti

2016

Current Opinion in Infectious Diseases

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Purpose of review The purpose of this review is to summarize and discuss recent findings and selected topics of interest in Bordetella pertussis virulence and pathogenesis and treatment of pertussis. It is not intended to cover issues on immune responses to B. pertussis infection or problems with currently used pertussis vaccines. Recent findings Studies on the activities of various B. pertussis virulence factors include the immunomodulatory activities of filamentous hemagglutinin, fimbriae, and adenylate cyclase toxin. Recently emerging B. pertussis strains show evidence of genetic selection for vaccine escape mutants, with changes in vaccine antigen-expressing genes, some of which may have increased the virulence of this pathogen. Severe and fatal pertussis in young infants continues to be a problem, with several studies highlighting predictors of fatality, including the extreme leukocytosis associated with this infection. Treatments for pertussis are extremely limited, though early antibiotic intervention may be beneficial. Neutralizing pertussis toxin activity may be an effective strategy, as well as targeting two host proteins, pendrin and sphingosine-1-phosphate receptors, as novel potential therapeutic interventions. Summary Pertussis is reemerging as a major public health problem and continued basic research is revealing information on bacterial virulence and disease pathogenesis, as well as potential novel strategies for vaccination and targets for therapeutic intervention.

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Filamentous Hemagglutinin of Bordetella Pertussis : a Key Adhesin with Immunomodulatory Properties?

Cited by 26 publications

References 150 publications

Glutamate Limitation, BvgAS Activation, and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System

Glutamate Limitation, BvgAS Activation, and (p)ppGpp Regulate the Expression of the Bordetella pertussis Type 3 Secretion System

Pseudomonas fluorescens Filamentous Hemagglutinin, an Iron-Regulated Protein, Is an Important Virulence Factor that Modulates Bacterial Pathogenicity

Bordetella pertussis

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