1/THREAD Have you ever wondered why Pseudomonas aeruginosa smells like grapes ? The answer relates to the ability of Pseudomonas to cause chronic airway infections and also coincidentally explains certain spoiled wine flavors. #medtwitter #tweetorial

2/ Pseudomonas was first isolated in 1882 by the French pharmacist Carle Gessard, after he cultured it from the blue-green pus on bandages of injured soldiers. academic.oup.com/cid/article/6/

3/ It was widely observed that Pseudomonas aeruginosa produces a grape-like smell when growing in cultures or on wounds. By the 1970s, microbiologists even used this characteristic odor to preliminarily identify Pseudomonas on agar plates. ncbi.nlm.nih.gov/pmc/articles/P

4/ The chemical source of Pseudomonas' grape-like smell was identified by Mann in 1966. He isolated a compound with a grape-ish odor from 20-day-old plate cultures of P. aeruginosa using thin layer chromatography. link.springer.com/article/10.100

5/ Mann discovered that the source of Pseudomonas' odor is a volatile organic compound called 2-aminoacetophenone (2-AA). 2-AA is a metabolite produced by the bacterium from the tryptophan catabolic pathway and, for whatever reason, smells like grapes. pubmed.ncbi.nlm.nih.gov/25960261/

6/ 2-AA has even been studied as a potential biomarker for Pseudomonal airway colonization/infection in cystic fibrosis (CF) patients. A breath test detecting exhaled 2-AA was 94% sensitive and 69% specific for airway Pseudomonas in a CF cohort. pubmed.ncbi.nlm.nih.gov/21054900/

7/ It isn't totally clear whether 2-AA plays a part in the ability of Pseudomonas to be a human pathogen, or if 2-AA is simply a grape-scented metabolite. But there is evidence that it might contribute to Pseudomonas' ability to cause chronic pulmonary airway infections.

8/ First, 2-AA may actually inhibit the immune response to Pseudomonal infection, allowing it to chronically colonize the airway. Pre-treatment with 2-AA in mice infected with Pseudomonas led to decreased inflammatory cytokine responses. pubmed.ncbi.nlm.nih.gov/23166496/

9/ Even more strikingly: In animal models 2-AA has been shown to modulate genetic expression in Pseudomonas in a way that favors persistent infection (decreased virulence and a longer lifespan). pubmed.ncbi.nlm.nih.gov/21829370/

10/ 2-AA's role in chronic Pseudomonal infection is still being worked out. The current model:

2-AA is released and accumulates in airway biofilms

This modulates immune response and genetic expression, allowing for chronic infection pubmed.ncbi.nlm.nih.gov/21829370/

11/ Let's conclude with a cool (and surprising) viticultural correlate. It turns out that 2-Aminoacetophenone (2-AA) is one source of spoiled wine flavor, as an unwanted post-fermentation metabolite from grapes, especially in white wines. sciencedirect.com/science/articl

12/ Wine spoiled by 2-AA has the flavor of "acacia blossom, naphthalene note, furniture polish, fusel alcohol, damp cloth...". This seems to be a more of a concern for vintners, as they will reject wine spoiled by 2-AA before sending to consumers. pubmed.ncbi.nlm.nih.gov/17014858/