The Bvg Virulence Control System Regulates Biofilm Formation in Bordetella bronchiseptica

Abstract

؉ phase encode known virulence factors, including adhesins such as filamentous hemagglutinin (FHA) and fimbriae, as well as toxins such as the bifunctional adenylate cyclase/hemolysin (ACY). Previous studies showed that in the Bvg i phase, FHA and fimbriae continue to be expressed, but ACY expression is significantly downregulated. In this report, we determine that Bordetella bronchiseptica can form biofilms in vitro and that the generation of biofilm is maximal in the Bvg i phase. We show that FHA is required for maximal biofilm formation and that fimbriae may also contribute to this phenotype. However, expression of ACY inhibits biofilm formation, most likely via interactions with FHA. Therefore, the coordinated regulation of adhesins and ACY expression leads to maximal biofilm formation in the Bvg i phase in B. bronchiseptica.Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related gram-negative coccobacilli that colonize the upper respiratory tract of mammals. B. pertussis and most B. parapertussis strains are obligate human pathogens that usually cause acute respiratory diseases. B. bronchiseptica has a much broader host range and is considered to be representative of the evolutionary progenitor of all Bordetella spp. (10, 27). It naturally infects many laboratory animals, including mice, rats, and rabbits, and thus serves as an ideal model for studying bacterial pathogenesis in a natural infection setting. Although B. bronchiseptica has been associated with various respiratory diseases, infection by this organism generally leads to chronic and asymptomatic colonization in the host. This lifestyle indicates that the bacteria employ specific mechanisms to counteract host immune responses and also implies successful interactions with other commensal bacteria commonly found in the upper respiratory tract.

Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis

“…In addition to this regulation, binding of BvgAS to the promoter is required for fim2 and fim3 expression (Chen et al, 2010). A fimBCD mutant of Bordetella bronchiseptica that expresses no fimbriae has severely defective biofilm formation in the Bvg + phase in spite of the fact that FHA contributes to biofilm development in the Bvg i phase of B. bronchiseptica (Irie et al, 2004). In the same study, it was found that the fimBCD mutant shows only a slight decrease in biofilm formation in the Bvg i phase.…”

Proteome approaches combined with Fourier transform infrared spectroscopy revealed a distinctive biofilm physiology in Bordetella pertussis

“…In Bordetella, BvgA, together with the sensor protein BvgS, integrates the BvgAS two-component system, which controls the expression of a complex array of virulence factors through a phosphorylation cascade in response to environmental stimuli [50]. The recent finding that the BvgAS system is involved in regulating biofilm formation [2,4,20] together with the results presented in this work, raise intriguing questions about the virulence phenotype of the sessile cells. Another interesting observation, which requires further attention, is the increased expression of Sadenosylmethionine synthetase in biofilm.…”

“…Although historically the occurrence of pertussis was associated with an acute infection, primarily in not-or under-immunized infants, a shift in the incidence of the disease towards adolescents and adults with the appearance of persistent asymptomatic or mild infections is becoming increasingly evident [1]. Recent reports support the hypothesis that B. pertussis could adopt a biofilm lifestyle as a strategy to colonize the host, but the mechanisms leading to persistent B. pertussis infections are largely unknown [2][3][4]. Biofilm is a community-based mode of existence of microbes in which cells are enclosed in a self-producing matrix and adhered to an inert or living surface [5].…”

The BvgAS Regulon of Bordetella pertussis

“…It has been speculated that the Bvg(i) and Bvg(Ϫ) modes may represent useless "evolutionary remnants" and that the BvgAS system may represent an evolutionary "fossil" in B. pertussis, necessary only for its role in activating virulence genes but not utilized to adjust virulence gene expression in response to environmental signals (9,22,28). Another point of view is that the BvgAS system, together with the genes expressed in the Bvg(Ϫ) and Bvg(i) modes, plays a role in B. pertussis different from that in B. bronchiseptica, such as in transmission by the aerosol route (29). In this regard, Bvg(Ϫ) mutants have been observed to accumulate among the B. pertussis population in the rhesus monkey nasopharynx, demonstrating that cells in the Bvg(Ϫ) mode may not be immediately cleared during infection (30).…”