Abstract
B. cenocepacia is an opportunistic human pathogen that is particularly problematic for patients suffering from cystic fibrosis (CF). In the CF lung bacteria grow to high densities within the viscous mucus that is limited in oxygen. Pseudomonas aeruginosa, the dominant pathogen in CF patients, is known to grow and survive under oxygen-limited to anaerobic conditions by using micro-oxic respiration, denitrification and fermentative pathways. In contrast, inspection of the genome sequences of available B. cenocepacia strains suggested that B. cenocepacia is an obligate aerobic and non-fermenting bacterium. In accordance with the bioinformatics analysis we observed that B. cenocepacia H111 is able to grow with as little as 0.1% O2 but not under strictly anoxic conditions. Phenotypic analyses revealed that H111 produced larger amounts of biofilm, pellicle and proteases under micro-oxic conditions (0.5%–5% O2, i.e. conditions that mimic those encountered in CF lung infection), and was more resistant to several antibiotics. RNA-Seq and shotgun proteomics analyses of cultures of B. cenocepacia H111 grown under micro-oxic and aerobic conditions showed up-regulation of genes involved in the synthesis of the exopolysaccharide (EPS) cepacian as well as several proteases, two isocitrate lyases and other genes potentially important for life in micro-oxia.Data deposition: RNA-Seq raw data files are accessible through the GEO Series accession number GSE48585. MS data have been deposited in the ProteomeXchange database (PXD000270).
Highlights
Burkholderia cenocepacia is one of the 17 members of the Burkholderia cepacia complex (Bcc) whose extraordinary metabolic versatility allows it to adapt to a variety of environmental conditions, including infection sites in humans [1,2]
B. cenocepacia was still able to grow with 0.1% oxygen with a doubling time of 268 minutes, reaching an OD600 of 0.7
At present very little is known of how B. cenocepacia strains can adapt to the micro-oxic/anoxic environment within biofilms in the cystic fibrosis (CF) lung [7,8,9,32]
Summary
Burkholderia cenocepacia is one of the 17 members of the Burkholderia cepacia complex (Bcc) whose extraordinary metabolic versatility allows it to adapt to a variety of environmental conditions, including infection sites in humans [1,2]. Several strains of the Bcc species B. multivorans, B. cenocepacia, B. cepacia, and B. dolosa have been shown to be highly transmissible between patients [4], with B. cenocepacia and B. multivorans accounting for the majority of CF infections [5]. B. cenocepacia produces biofilms and uses the highly viscous mucus of the CF lung as a rich nutrient source. Due to bacterial respiration a steep oxygen gradient within the mucus is generated and the deeper layers become anaerobic [7,8,9,10]. This observation is supported by the fact that anaerobes have been found to occur in CF sputum at high cell densities [11]. P. aeruginosa can use pyruvate fermentation for long-term survival of up to 18 days under anoxic conditions and this conversion of pyruvate into lactate, acetate, and succinate is in turn inhibited by nitrate respiration [19]
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