Abstract
Burkholderia cenocepacia is an opportunistic pathogen associated with chronic lung infections and increased risk of death in patients with cystic fibrosis (CF). In this work, we investigated the lipopolysaccharide (LPS) of clinical variants of B. cenocepacia that were collected from a CF patient over a period of 3.5 years, from the onset of infection until death by necrotizing pneumonia (cepacia syndrome). We report the chemical structure of the LPS molecule of various sequential isolates and the identification of a novel hybrid O-antigen (OAg) biosynthetic cluster. The OAg repeating unit of the LPS from IST439, the initial isolate, is a [→2)-β-D-Ribf-(1→4)-α-D-GalpNAc-(1→] disaccharide, which was not previously described in B. cenocepacia. The IST439 OAg biosynthetic gene cluster contains 7 of 23 genes that are closely homologous to genes found in B. multivorans, another member of the Burkholderia cepacia complex. None of the subsequent isolates expressed OAg. Genomic sequencing of these isolates enabled the identification of mutations within the OAg cluster, but none of these mutations could be associated with the loss of OAg. This study provides support to the notion that OAg LPS modifications are an important factor in the adaptation of B. cenocepacia to chronic infection and that the heterogeneity of OAgs relates to variation within the OAg gene cluster, indicating that the gene cluster might have been assembled through multiple horizontal transmission events.
Highlights
Burkholderia cenocepacia is a Gram-negative opportunistic human pathogen of the Burkholderia cepacia complex (Bcc), relevant in immunocompromised individuals and cystic fibrosis (CF) patients (Mahenthiralingam et al, 2002, 2005)
Our results reveal that the early B. cenocepacia IST439 isolate encodes a functional genetic cluster responsible for OAg biosynthesis, with a hybrid composition including genes highly homologous to B. multivorans genes
The banding pattern of the OAg in IST439 was distinct from that in the strain K56-2 (Supplementary Figure S1). Both IST439 and K56-2 belong to the same B. cenocepacia clonal group2 they produce seemingly different OAg molecules
Summary
Burkholderia cenocepacia is a Gram-negative opportunistic human pathogen of the Burkholderia cepacia complex (Bcc), relevant in immunocompromised individuals and cystic fibrosis (CF) patients (Mahenthiralingam et al, 2002, 2005). LPS is a major component of the Gram-negative bacterial outer membrane, which participates in host–bacterium interactions, such as adhesion, immune evasion, persistence, and antimicrobial resistance (Raetz and Whitfield, 2002; De Soyza et al, 2008; Valvano et al, 2011; Maldonado et al, 2016). LPS consists of a core oligosaccharide (core) that is covalently linked to a lipophilic glycan termed lipid A (Whitfield and Trent, 2014). The core, subdivided into inner and outer core, comprises conserved monosaccharide residues, such as heptoses and 3-deoxy-Dmanno-oct-2-ulosonic acid (Kdo), which are typically unique to the LPS molecule (Whitfield and Trent, 2014). The OAg extends away from the outer membrane surface becoming exposed to the extracellular milieu; it is composed of linear or branched homo- or heteropolysaccharides of variable length, with subunits consisting of up to eight different sugars (Valvano et al, 2011)
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