What Makes Us Smell: The Biochemistry of Body Odour and the Design of New Deodorant Ingredients

Today, axilla odours are socially stigmatized and are targeted with deodorants and antiperspirants representing a multi-billion market. Axilla odours aren't simple byproducts of our metabolism but specifically formed by an intricate interplay between i) specific glands, ii) secreted amino acid conjugates of highly specific odorants and iii) selective enzymes present in microorganisms colonizing our skin, providing a natural 'controlled-release' mechanism. Within a multidisciplinary research project, we were able to elucidate the structure of key body odorants, isolate and characterize secreted amino acid conjugates and identify the enzymes responsible for odour release. These enzymes then served as targets for the development of specific active compounds in an almost medicinal chemistry approach, an approach rarely used in the cosmetic field so far. Here we review the key new insights into the biochemistry of human body odour formation, with some remarks on the experimental steps undertaken and hurdles encountered. The development of deodorant actives and the difficult path to market for such specifically acting cosmetic actives is discussed. The basic insights into the biochemistry also opened the way to address some questions in population genetics: Why have large proportions of Asians lost the 'ability' to form body odours? Do twins smell the same? Are our typical body odours indeed influenced by the immune system as often claimed? After addressing these questions, I'll conclude with the key remaining challenges in this field on an ecological niche that is 'anatomically very close to our heart'

Impact of Pseudomonas fluorescens strain CHA0 and a derivative with improved biocontrol activity on the culturable resident bacterial community on cucumber roots

Information on the effects of released wild-type or genetically engineered bacteria on resident bacterial communities is important to assess the potential risks associated with the introduction of these organisms into agroecosystems. The rifampicin-resistant biocontrol strain Pseudomonas fluorescens CHA0-Rif and its derivative CHA0-Rif/pME3424, which has improved biocontrol activity and enhanced production of the antibiotics 2,4-diacetylphloroglucinol (Phl) and pyoluteorin (Plt), were introduced into soil microcosms and the culturable bacterial community developing on cucumber roots was investigated 10 and 52 days later. The introduction of either of the two strains led to a transiently enhanced metabolic activity of the bacterial community on glucose dimers and polymers as measured with BIOLOG GN plates, but natural succession between the two sampling dates changed the metabolic activity of the bacterial community more than did the inoculants. The introduced strains did not significantly affect the abundance of dominant genotypic groups of culturable bacteria discriminated by restriction analysis of amplified 16S rDNA of 2500 individual isolates. About 30-50% of the resident bacteria were very sensitive to Phl and Plt, but neither the wild-type nor CHA0-Rif/pME3424 changed the proportion of sensitive and resistant bacteria in situ. In microcosms with a synthetic bacterial community, both biocontrol strains reduced the population of a strain of Pseudomonas but did not affect the abundance of four other bacterial strains including two highly antibiotic-sensitive isolates. We conclude that detectable perturbations in the metabolic activity of the resident bacterial community caused by the biocontrol strain CHA0-Rif are (i) transient, (ii) similar for the genetically improved derivative CHA0-Rif/pME3424 and (iii) less pronounced than changes in the community structure during plant growt

Autecology of the biocontrol strain Pseudomonas fluorescens CHA0 in the rhizosphere and inside roots at later stages of plant development

A spontaneous rifampicin-resistant mutant of the biocontrol agent Pseudomonas fluorescens CHA0 was released as soil inoculant in large outdoor lysimeters and its ability to colonise the roots of winter wheat, spring wheat (grown after Phacelia) and maize at the later stages of plant development was investigated by colony counts. The inoculant (i.e. CHA0-Rif) colonised the rhizosphere and the interior of the roots of both wheat varieties but CFUs at ripening were about 2 log (g root)−1 or lower. In contrast, the roots of maize were colonised poorly by the pseudomonad at flowering, but the latter was found at 3 or more log CFU (g root)−1 on and inside the roots in late ripening stage. Furthermore, CHA0-Rif was recovered at more than 5 log CFU (g root)−1 from the interior of several maize root samples. Whereas most cells of CHA0-Rif in soil were small and did not respond to Kogure's viability test, the pseudomonad was present as viable, unusually large (7 mm long) rods inside maize roots. In a microcosm experiment performed with similar sandy-loam soil, the CFUs of maize root-associated CHA0-Rif were higher where the shoots of the plant had been cut off, confirming that older and/or decaying maize roots represent a favourable niche for the inoculant. Overall, the results indicate that Pseudomonas inoculants have the potential to colonise the roots of certain crops (e.g. maize but not wheat for strain CHA0-Rif) at later stages of plant developmen

A Functional ABCC11 Allele Is Essential in the Biochemical Formation of Human Axillary Odor

The characteristic human axillary odor is formed by bacterial action on odor precursors that originate from apocrine sweat glands. Caucasians and Africans possess a strong axillary odor ,whereas many Asians have only a faint acidic odor. In this study, we provide evidence that the gene ABCC11 (MRP8), which encodes an apical efflux pump, is crucial for the formation of the characteristic axillary odor and that a single-nucleotide polymorphism (SNP) 538G → A, which is prominent among Asian people, leads to a nearly complete loss of the typical odor components in axillary sweat. The secretion of amino-acid conjugates of human-specific odorants is abolished in homozygotic carriers of the SNP, and steroidal odorants and their putative precursors are significantly reduced. Moreover, we show that ABCC11 is expressed and localized in apocrine sweat glands. These data point to a key function of ABCC11 in the secretion of odorants and their precursors from apocrine sweat glands. SNP 538G → A, which also determines human earwax type, is present on an extended haplotype, which has reached >95% frequency in certain populations in recent human evolution. A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of-function allele

Cosmopolitan distribution of phlD-containing dicotyledonous crop-associated biocontrol pseudomonads of worldwide origin

In biocontrol fluorescent pseudomonads, phlD encodes a polyketide synthase required for the synthesis of the antifungal compound 2,4-diacetylphloroglucinol (Phl). Here, PCR-restriction fragment length polymorphism analysis was used to compare phlD alleles in 77 dicot-associated pseudomonads originating from various countries worldwide and 10 counterparts from a monocotyledonous host (wheat). The 16 restriction patterns obtained were mostly unrelated to geographic location or dicot host. Cluster analysis distinguished eight phlD clusters at a similarity level of 0.63. One cluster grouped 18 pseudomonads that produced also the antifungal polyketide pyoluteorin but could not assimilate D-galactose, D-galactonate lactone, D-sorbitol, L-arabinose, D-saccharate or D-xylose. These 18 pseudomonads, along with the eight pseudomonads from a second phlD cluster, were the only isolates that failed to deaminase 1-aminocyclopropane-1-carboxylate (ACC), a rare root growth promotion trait. Overall, assessment of phlD polymorphism, ACC deaminase activity and catabolic profiles pointed to a cosmopolitan distribution of Phl-producing biocontrol fluorescent pseudomonads of worldwide origin associated with dicotyledonous crop plant

Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: an analytical market surveillance

International audienc

t4 Workshop Report: Integrated Testing Strategies (ITS) for Safety Assessment

Integrated testing strategies (ITS), as opposed to single definitive tests or fixed batteries of tests, are expected to efficiently combine different information sources in a quantifiable fashion to satisfy an information need, in this case for regulatory safety assessments. With increasing awareness of the limitations of each individual tool and the development of highly targeted tests and predictions, the need for combining pieces of evidence increases. The discussions that took place during this workshop, which brought together a group of experts coming from different related areas, illustrate the current state of the art of ITS, as well as promising developments and identifiable challenges. The case of skin sensitization was taken as an example to understand how possible ITS can be constructed, optimized and validated. This will require embracing and developing new concepts such as adverse outcome pathways (AOP), advanced statistical learning algorithms and machine learning, mechanistic validation and “Good ITS Practices”.JRC.I.5-Systems Toxicolog

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades

Influence of biocontrol strain Pseudomonas fluorescens CHA0 and its antibiotic overproducing derivative on the diversity of resident root colonizing pseudomonads

Non-target effects of biocontrol strains of Pseudomonas on the population of resident pseudomonads should be assessed prior to their large scale application in the environment. The rifampicin resistant bacterium P. fluorescens CHA0-Rif and its antibiotic overproducing derivative CHA0-Rif/pME3424 were introduced into soil microcosms and the population of resident pseudomonads colonizing cucumber roots was investigated after 10 and 52 days. Both CHA0-Rif and CHA0-Rif/pME3424 displaced a part of the resident pseudomonad population after 10 days. To investigate the population structure, utilization of 10 carbon sources and production of two exoenzymes was assessed for 5600 individual pseudomonad isolates and 1700 isolates were subjected to amplified ribosomal DNA restriction analysis of the spacer region (spacer-ARDRA). After 10 days, only the proportion of pseudomonads able to degrade l-tryptophan was reduced in treatments inoculated with either biocontrol strain. In parallel the phenotypic diversity was reduced. These effects were only observed 10 days after inoculation, and they were similar for inoculation with CHA0-Rif and CHA0-Rif/pME3424. Changes in the population structure of resident pseudomonads on cucumber roots during plant growth were more pronounced than changes due to the inoculants. The inoculants did not affect the genotypic diversity detected with spacer-ARDRA, but the genotypic fingerprints corresponded only partially to the phenotypic profiles. Overall CHA0-Rif had a small and transient impact on the population of resident pseudomonads and the effect was essentially the same for the genetically engineered derivative CHA0-Rif/pME342