Abstract
Burkholderia dolosa caused an outbreak in the cystic fibrosis clinic at Boston Children’s Hospital and was associated with high mortality in these patients. This species is part of a larger complex of opportunistic pathogens known as the Burkholderia cepacia complex (Bcc). Compared to other species in the Bcc, B. dolosa is highly transmissible; thus understanding its virulence mechanisms is important for preventing future outbreaks. The genome of one of the outbreak strains, AU0158, revealed a homolog of the lafA gene encoding a putative lateral flagellin, which, in other non-Bcc species, is used for movement on solid surfaces, attachment to host cells, or movement inside host cells. Here, we analyzed the conservation of the lafA gene and protein sequences, which are distinct from those of the polar flagella, and found lafA homologs to be present in numerous β-proteobacteria but notably absent from most other Bcc species. A lafA deletion mutant in B. dolosa showed a greater swimming motility than wild-type due to an increase in the number of polar flagella, but did not appear to contribute to biofilm formation, host cell invasion, or murine lung colonization or persistence over time. However, the lafA gene was important for cytokine production in human peripheral blood mononuclear cells, suggesting it may have a role in recognition by the human immune response.
Highlights
Cystic fibrosis (CF) has a prevalence of ~1/3,000 live Caucasian births, making it a commonly inherited disorder leading to a limited lifespan and high morbidity [1]
The flgBDEFGHIJKL genes are common located together in polar and lateral flagella systems (Fig 1); the location of the B. dolosa lafA gene is found next to the fliM gene rather than next to the lafB gene as in A. hydrophila or the fliD gene in V. parahaemolyticus
The discovery of the lateral flagellin system in B. dolosa is surprising in that it has yet to be reported in any other Burkholderia cepacia complex (Bcc) species, despite the plethora of genomes available for this group
Summary
Cystic fibrosis (CF) has a prevalence of ~1/3,000 live Caucasian births, making it a commonly inherited disorder leading to a limited lifespan and high morbidity [1]. Members of the Bcc are capable of producing a necrotizing pneumonia in infected patients, characterized by a rapid decline in lung function (1–3 months) with bacteremia and near 100% mortality. This is often called the “cepacia syndrome” [5]. The most common outbreak strains capable of spreading between CF patients fall within the B. cenocepacia and B. dolosa species [9]. These outbreaks have resulted in the enforcement of strict regulations and segregation for CF patients. One of the outbreaks occurred at Boston Children’s Hospital, in which B. dolosa infected over 40 patients and contributed to the death of many, if not all, of them [10]
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