Volatile Metabolites of Pathogens: A Systematic Review

Ideally, invading bacteria are detected as early as possible in critically ill patients: the strain of morbific pathogens is identified rapidly, and antimicrobial sensitivity is known well before the start of new antimicrobial therapy. Bacteria have a distinct metabolism, part of which results in the production of bacteria-specific volatile organic compounds (VOCs), which might be used for diagnostic purposes. Volatile metabolites can be investigated directly in exhaled air, allowing for noninvasive monitoring. The aim of this review is to provide an overview of VOCs produced by the six most abundant and pathogenic bacteria in sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Such VOCs could be used as biological markers in the diagnostic approach of critically ill patients. A systematic review of existing literature revealed 31 articles. All six bacteria of interest produce isopentanol, formaldehyde, methyl mercaptan, and trimethylamine. Since humans do not produce these VOCs, they could serve as biological markers for presence of these pathogens. The following volatile biomarkers were found for identification of specific strains: isovaleric acid and 2-methyl-butanal for Staphylococcus aureus; 1-undecene, 2,4-dimethyl-1-heptane, 2-butanone, 4-methyl-quinazoline, hydrogen cyanide, and methyl thiocyanide for Pseudomonas aeruginosa; and methanol, pentanol, ethyl acetate, and indole for Escherichia coli. Notably, several factors that may effect VOC production were not controlled for, including used culture media, bacterial growth phase, and genomic variation within bacterial strains. In conclusion, VOCs produced by bacteria may serve as biological markers for their presence. Goal-targeted studies should be performed to identify potential sets of volatile biological markers and evaluate the diagnostic accuracy of these markers in critically ill patients.

[1]  G. Schelling,et al.  Volatile compound profiling for the identification of Gram‐negative bacteria by ion‐molecule reaction–mass spectrometry , 2012, Journal of applied microbiology.

[2]  Hossam Haick,et al.  Volatile organic compounds of lung cancer and possible biochemical pathways. , 2012, Chemical reviews.

[3]  J. O’Horo,et al.  Is the gram stain useful in the microbiologic diagnosis of VAP? A meta-analysis. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  Heather D. Bean,et al.  Bacterial volatile discovery using solid phase microextraction and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[5]  G. Schelling,et al.  Volatile organic compound analysis by ion molecule reaction mass spectrometry for Gram-positive bacteria differentiation , 2012, European Journal of Clinical Microbiology & Infectious Diseases.

[6]  Anton Amann,et al.  Molecular analysis of volatile metabolites released specifically by staphylococcus aureus and pseudomonas aeruginosa , 2012, BMC Microbiology.

[7]  F. V. van Schooten,et al.  The versatile use of exhaled volatile organic compounds in human health and disease , 2012, Journal of breath research.

[8]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[9]  W. Vautz,et al.  Ion mobility spectrometry for microbial volatile organic compounds: a new identification tool for human pathogenic bacteria , 2012, Applied Microbiology and Biotechnology.

[10]  A. Del Arco,et al.  Impact of Inadequate Empirical Therapy on the Mortality of Patients with Bloodstream Infections: a Propensity Score-Based Analysis , 2011, Antimicrobial Agents and Chemotherapy.

[11]  Malina K. Storer,et al.  Detection of volatile compounds produced by microbial growth in urine by selected ion flow tube mass spectrometry (SIFT-MS). , 2011, Journal of microbiological methods.

[12]  V. Shestivska,et al.  Quantification of methyl thiocyanate in the headspace of Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis patients by selected ion flow tube mass spectrometry. , 2011, Rapid communications in mass spectrometry : RCM.

[13]  J. Pearson,et al.  Potential sources of 2-aminoacetophenone to confound the Pseudomonas aeruginosa breath test, including analysis of a food challenge study , 2011, Journal of breath research.

[14]  P. Corris,et al.  Volatile biomarkers of Pseudomonas aeruginosa in cystic fibrosis and noncystic fibrosis bronchiectasis , 2011, Letters in applied microbiology.

[15]  Avijit Sen,et al.  Rapid identification of bacteria with a disposable colorimetric sensing array. , 2011, Journal of the American Chemical Society.

[16]  T. Welte,et al.  Will polymerase chain reaction (PCR)-based diagnostics improve outcome in septic patients? A clinical view , 2011, Intensive Care Medicine.

[17]  G. Barlow,et al.  Diagnostic and prognostic biomarkers of sepsis in critical care. , 2011, The Journal of antimicrobial chemotherapy.

[18]  S. Chambers,et al.  Novel diagnostics: progress toward a breath test for invasive Aspergillus fumigatus. , 2011, Medical mycology.

[19]  J. Greenman,et al.  Multivariate analysis of bacterial volatile compound profiles for discrimination between selected species and strains in vitro. , 2011, Journal of microbiological methods.

[20]  Alphus D. Wilson,et al.  Advances in Electronic-Nose Technologies Developed for Biomedical Applications , 2011, Sensors.

[21]  Yongjun Feng,et al.  Indole Affects Biofilm Formation in Bacteria , 2010, Indian Journal of Microbiology.

[22]  R. Laing,et al.  2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung , 2010, BMC pulmonary medicine.

[23]  Jiangjiang Zhu,et al.  Fast Detection of Volatile Organic Compounds from Bacterial Cultures by Secondary Electrospray Ionization-Mass Spectrometry , 2010, Journal of Clinical Microbiology.

[24]  Anton Amann,et al.  Methodological issues of sample collection and analysis of exhaled breath , 2010 .

[25]  J. Vincent,et al.  Sepsis biomarkers: a review , 2010, Critical care.

[26]  Lior Pachter,et al.  Disordered Microbial Communities in Asthmatic Airways , 2010, PloS one.

[27]  Jordi Rello,et al.  International study of the prevalence and outcomes of infection in intensive care units. , 2009, JAMA.

[28]  Alan Gelperin,et al.  Volatile compounds characteristic of sinus-related bacteria and infected sinus mucus: analysis by solid-phase microextraction and gas chromatography-mass spectrometry. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[29]  Jörg Ingo Baumbach,et al.  Detection of volatile metabolites of Escherichia coli by multi capillary column coupled ion mobility spectrometry , 2009, Analytical and bioanalytical chemistry.

[30]  M. Friedrich,et al.  Scientists seek to sniff out diseases: electronic "noses" may someday be diagnostic tools. , 2009, JAMA.

[31]  Jay Steingrub,et al.  International study of the prevalence and outcomes of infection in intensive care units , 2009 .

[32]  J. Lindon,et al.  Systems biology: Metabonomics , 2008, Nature.

[33]  G. Schelling,et al.  Molecular breath-gas analysis by online mass spectrometry in mechanically ventilated patients: a new software-based method of CO2-controlled alveolar gas monitoring , 2008, Journal of breath research.

[34]  S. Chambers,et al.  Investigation into the production of 2-Pentylfuran by Aspergillus fumigatus and other respiratory pathogens in vitro and human breath samples. , 2008, Medical mycology.

[35]  Tomas Mikoviny,et al.  On-Line Monitoring of Microbial Volatile Metabolites by Proton Transfer Reaction-Mass Spectrometry , 2008, Applied and Environmental Microbiology.

[36]  N. Bârsan,et al.  Electronic nose: current status and future trends. , 2008, Chemical reviews.

[37]  Jeroen S. Dickschat,et al.  Bacterial volatiles: the smell of small organisms. , 2007, Natural product reports.

[38]  P. Xu,et al.  Acetoin Metabolism in Bacteria , 2007, Critical reviews in microbiology.

[39]  David R Murdoch,et al.  The rapid evaluation of bacterial growth and antibiotic susceptibility in blood cultures by selected ion flow tube mass spectrometry. , 2006, Diagnostic microbiology and infectious disease.

[40]  D. Murdoch,et al.  The rapid evaluation of bacterial growth in blood cultures by selected ion flow tube-mass spectrometry (SIFT-MS) and comparison with the BacT/ALERT automated blood culture system. , 2006, Journal of microbiological methods.

[41]  K. Wood,et al.  Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock* , 2006, Critical care medicine.

[42]  Conrad Bessant,et al.  Prospects for Clinical Application of Electronic-Nose Technology to Early Detection of Mycobacterium tuberculosis in Culture and Sputum , 2006, Journal of Clinical Microbiology.

[43]  David R Murdoch,et al.  Detection of volatile metabolites produced by bacterial growth in blood culture media by selected ion flow tube mass spectrometry (SIFT-MS). , 2006, Journal of microbiological methods.

[44]  P. Španěl,et al.  Bronchoalveolar lavage examined by solid phase microextraction, gas chromatography--mass spectrometry and selected ion flow tube mass spectrometry. , 2006, Journal of microbiological methods.

[45]  J. Struck,et al.  Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study , 2005, Critical care.

[46]  M. McEwan,et al.  Real-time detection of common microbial volatile organic compounds from medically important fungi by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS). , 2005, Journal of microbiological methods.

[47]  David Smith,et al.  Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. , 2005, Mass spectrometry reviews.

[48]  Keshun Yu,et al.  Production of the Long-Chain Alcohols Octanol, Decanol, and Dodecanol by Escherichia coli , 2005, Current Microbiology.

[49]  David Smith,et al.  Detection of volatile compounds emitted by Pseudomonas aeruginosa using selected ion flow tube mass spectrometry , 2005, Pediatric pulmonology.

[50]  W. Pollock,et al.  Bacteria produce the volatile hydrocarbon isoprene , 1995, Current Microbiology.

[51]  L. Bret,et al.  Indole can act as an extracellular signal to regulate biofilm formation of Escherichia coli and other indole-producing bacteria. , 2003, Canadian journal of microbiology.

[52]  Karin Greiner,et al.  Elective haemodialysis increases exhaled isoprene. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[53]  D. Mannino,et al.  The epidemiology of sepsis in the United States from 1979 through 2000. , 2003, The New England journal of medicine.

[54]  D. Rennie,et al.  Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative , 2003, BMJ : British Medical Journal.

[55]  J. Julák,et al.  Evaluation of exudates by solid phase microextraction-gas chromatography. , 2003, Journal of microbiological methods.

[56]  J. Gardner,et al.  Biomedical Engineering Online Open Access Bacteria Classification Using Cyranose 320 Electronic Nose , 2022 .

[57]  W. Miekisch,et al.  Breath Markers and Soluble Lipid Peroxidation Markers in Critically Ill Patients , 2002, Clinical chemistry and laboratory medicine.

[58]  B. Littenberg,et al.  Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[59]  T. Koga,et al.  Formation of Methyl Mercaptan froml-Methionine by Porphyromonas gingivalis , 2000, Infection and Immunity.

[60]  J. Julák,et al.  Blood cultures evaluation by gas chromatography of volatile fatty acids. , 2000, Medical science monitor : international medical journal of experimental and clinical research.

[61]  B. Souweine,et al.  Comparison of direct examination of three types of bronchoscopy specimens used to diagnose nosocomial pneumonia , 2000, Critical care medicine.

[62]  R. Fall,et al.  Isoprene biosynthesis in Bacillus subtilis via the methylerythritol phosphate pathway. , 2000, Journal of natural products.

[63]  J. Schubert,et al.  Application of a new method for analysis of exhaled gas in critically ill patients , 1998, Intensive Care Medicine.

[64]  S. Molin,et al.  Volatile metabolites from some gram-negative bacteria. , 1997, Chemosphere.

[65]  S. Knøchel,et al.  Antimicrobial activity of food‐related Penicillium sp. against pathogenic bacteria in laboratory media and a cheese model system , 1997, Journal of applied microbiology.

[66]  I. Kubo,et al.  Structural functions of antimicrobial long-chain alcohols and phenols. , 1995, Bioorganic & medicinal chemistry.

[67]  P. Rutgeerts,et al.  Influence of nutritional substrates on the formation of volatiles by the fecal flora. , 1991, Gastroenterology.

[68]  L Goldman,et al.  Contaminant blood cultures and resource utilization. The true consequences of false-positive results. , 1991, JAMA.

[69]  G. Görgen,et al.  Biosynthesis of 1-alkenes in higher plants: stereochemical implications. A model study with Carthamus tinctorius (Asteraceae). , 1989, European journal of biochemistry.

[70]  P. Ney,et al.  Biosynthesis of 1-alkenes in higher plants. A model study with the composite Carthamus tinctorius L. , 1987, European journal of biochemistry.

[71]  J. Labows,et al.  Characterization of pathogenic bacteria by automated headspace concentration-gas chromatography. , 1986, Journal of chromatography.

[72]  N J Hayward,et al.  Volatile products from acetylcholine as markers in the rapid urine test using head-space gas-liquid chromatography. , 1984, Journal of chromatography.

[73]  M. Novotny,et al.  Urinary profiles of volatile and acid metabolites in germfree and conventional rats. , 1983, Life sciences.

[74]  B. Watt,et al.  Gas-liquid chromatography in the diagnosis of anaerobic infections: a three year experience. , 1982, Journal of clinical pathology.

[75]  B. Watt,et al.  Can direct gas-liquid chromatography of clinical samples detect specific organisms? , 1982, Journal of clinical pathology.

[76]  J. Leyden,et al.  Headspace analysis of volatile metabolites of Pseudomonas aeruginosa and related species by gas chromatography-mass spectrometry , 1980, Journal of clinical microbiology.

[77]  C. D. Cox,et al.  Use of 2-aminoacetophenone production in identification of Pseudomonas aeruginosa , 1979, Journal of clinical microbiology.

[78]  N J Hayward,et al.  Development of specific tests for rapid detection of Escherichia coli and all species of Proteus in urine , 1977, Journal of clinical microbiology.

[79]  Brooksby Jb.  Detection of bacterial metabolites in spent culture media and body fluids by electron capture gas-liquid chromatography. , 1977 .

[80]  J. B. Brooks.  Detection of bacterial metabolites in spent culture media and body fluids by electron capture gas-liquid chromatography. , 1977, Advances in chromatography.

[81]  P. Anema,et al.  Volatile acid production by Clostridium sporogenes under controlled culture conditions. , 1973, The Journal of applied bacteriology.

[82]  B. Shaw.  ON THE PRODUCTION OF FORMALDEHYDE BY INTESTINAL BACTERIA , 1924, British medical journal.