| Title: | Volatile fingerprinting of Pseudomonas aeruginosa and respiratory syncytial virus infection in an in vitro cystic fibrosis co-infection model |
| Author(s): | Purcaro G; Rees CA; Melvin JA; Bomberger JM; Hill JE; |
| Address: | "Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, United States of America" |
| ISSN/ISBN: | 1752-7163 (Electronic) 1752-7155 (Print) 1752-7155 (Linking) |
| Abstract: | "Volatile molecules in exhaled breath represent potential biomarkers in the setting of infectious diseases, particularly those affecting the respiratory tract. In particular, Pseudomonas aeruginosa is a critically important respiratory pathogen in specific subsets of the population, such as those with cystic fibrosis (CF). Infections caused by P. aeruginosa can be particularly problematic when co-infection with respiratory syncytial virus (RSV) occurs, as this is correlated with the establishment of chronic P. aeruginosa infection. In the present study, we evaluate the volatile metabolites produced by P. aeruginosa (PAO1)-infected, RSV-infected, co-infected, or uninfected CF bronchial epithelial (CFBE) cells, in vitro. We identified a volatile metabolic signature that could discriminate between P. aeruginosa-infected and non-P. aeruginosa-infected CFBE with an area under the receiver operating characteristic curve (AUROC) of 0.850, using the machine learning algorithm random forest (RF). Although we could not discriminate between RSV-infected and non-RSV-infected CFBE (AUROC = 0.431), we note that sample classification probabilities for RSV-infected cell, generated using RF, were between those of uninfected CFBE and P. aeruginosa-infected CFBE, suggesting that RSV infection may result in a volatile metabolic profile that shares attributes with both of these groups. To more precisely elucidate the biological origins of the volatile metabolites that were discriminatory between P. aeruginosa-infected and non-P. aeruginosa-infected CFBE, we measured the volatile metabolites produced by P. aeruginosa grown in the absence of CFBE. Our findings suggest that the discriminatory metabolites produced likely result from the interaction of P. aeruginosa with the CFBE cells, rather than the metabolism of media components by the bacterium. Taken together, our findings support the notion that P. aeruginosa interacting with CFBE yields a particular volatile metabolic signature. Such a signature may have clinical utility in the monitoring of individuals with CF" |
| Keywords: | Area Under Curve Coinfection/*diagnosis/microbiology/virology Cystic Fibrosis/*diagnosis/*microbiology Humans Metabolome Probability Pseudomonas Infections/*diagnosis Pseudomonas aeruginosa/growth & development/*metabolism ROC Curve Respiratory Syncytial; |
| Notes: | "MedlinePurcaro, Giorgia Rees, Christiaan A Melvin, Jeffrey A Bomberger, Jennifer M Hill, Jane E eng R01 HL123771/HL/NHLBI NIH HHS/ R21 AI121076/AI/NIAID NIH HHS/ T32 AI049820/AI/NIAID NIH HHS/ T32 LM012204/LM/NLM NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2018/05/08 J Breath Res. 2018 Jul 3; 12(4):046001. doi: 10.1088/1752-7163/aac2f1" |
