The first whiff of infection

Whiff: n. a slight trace of odour or smell

Many infective agents have a recognisable smell. When grown in pure culture on solid agar media they produce volatile organic compounds, some of which are characteristic of a particular species. You don’t need a very sensitive nose to pick up the whiff of Proteus mirabilis (ammonia and other volatile products associated with swarming growth)[1], or the caramel smell of the anginosus-constellatus-intermedius group of streptococci (formerly known as Streptococcus milleri) [2,3].

The pungent smell of bad breath comes from methylmercaptan and Hydrogen Sulphide generated by bacterial metabolism [4]. The whiff of the sea and the smell of soil are less noxious olfactory experiences that also have a metabolomic explanation. They both give off volatile sulphur compounds.

The so-called whiff test is used in the clinic to infer the presence of genitourinary infection without the need for subsequent culture-based laboratory investigation [5]. More recently analytical chemistry methods have been applied to detect bacterial metabolic products directly from the patient [6]. As sensitivity and specificity improves, these methods are being tried for early detection of bacterial infection. A series of laboratory studies has shown that common bacterial lung infections can be detected by GCMS analysis of exhaled breath [7,8].

This first whiff approach has already been used to detect Helicobacter [9]; an infective agent for which a breath test has long been in use. Other infections claimed to be detectable by exhaled breath test include tuberculosis, hospital-acquired pneumonia and chronic lung infection. Proponents of breath testing for bacterial infection observe that conventional specimens are prone to contamination by misleading oral bacteria, making culture-based methods unreliable. Detection of bacterial metabolic products, on the other hand, should depend on total bacterial activity. So the argument goes that it should be possible to identify bacterial metabolic markers in exhaled breath for specific infections as

  1. a specific measure of acute infection
  2. an indication of response to therapy, and
  3. an early warning of treatment failure

So, with a nod towards Dr Johnson; You smell, bacteria stink.


  1. Proteus mirabilis interkingdom swarming signals attract blow flies. Ma Q, Fonseca A, Liu W, Fields AT, Pimsler ML, Spindola AF, Tarone AM, Crippen TL, Tomberlin JK, Wood TK. ISME J. 2012 Jul;6(7):1356-66.
  2. Lancefield grouping and smell of caramel for presumptive identification and assessment of pathogenicity in the Streptococcus milleri group. Brogan O, Malone J, Fox C, Whyte AS. J Clin Pathol. 1997 Apr;50(4):332-5.
  3. Detection of diacetyl (caramel odor) in presumptive identification of the “Streptococcus milleri” group. Chew TA, Smith JM. J Clin Microbiol. 1992 Nov;30(11):3028-9.
  4. Production and origin of oral malodor: a review of mechanisms and methods of analysis. Tonzetich J. J Periodontol. 1977 Jan;48(1):13-20.
  5. Utility of pH test & Whiff test in syndromic approach of abnormal vaginal discharge. Thulkar J, Kriplani A, Agarwal N. Indian J Med Res. 2010 Mar;131:445-8.
  6. Robust detection of P. aeruginosa and S. aureus acute lung infections by secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting: from initial infection to clearance. Zhu J, Jiménez-Díaz J, Bean HD, Dapthary NA, Aliyeva MI, Lundblad LK, Hill JE. J Breath Res. 2013 Jul 18;7(3):037106.
  7. Secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting of multiple bacterial lung pathogens, a mouse model study. Zhu J, Bean HD, Jiménez-Díaz J, Hill JE. J Appl Physiol. 2013 Jun;114(11):1544-9.
  8. Detecting bacterial lung infections: in vivo evaluation of in vitro volatile fingerprints. Zhu J, Bean HD, Wargo MJ, Leclair LW, Hill JE. J Breath Res. 2013 Mar;7(1):016003.
  9. Process for detecting Helicobacter pylori using aliphatic amides. Ferreira JA, Dias E, Rocha SM, Coimbra MA. Anal Bioanal Chem. 2011 Oct;401(6):1889-98.


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