Chemistry:Staphyloxanthin

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Staphyloxanthin is a carotenoid pigment that is produced by some strains of Staphylococcus aureus, and is responsible for the characteristic golden color that gives S. aureus its species name. Staphyloxanthin also acts as a virulence factor.[1][2] It has an antioxidant action that helps the microbe evade death by reactive oxygen species produced by the host immune system.[1]

The pigment staphyloxanthin gave the bacteria Staphylococcus aureus a yellow color.

When comparing a normal strain of S. aureus with a strain modified to lack staphyloxanthin, the wildtype pigmented strain was more likely to survive incubation with an oxidizing chemical such as hydrogen peroxide than the mutant strain was. Colonies of the two strains were also exposed to human neutrophils. The mutant colonies quickly succumbed while many of the pigmented colonies survived. Wounds on mice were inoculated with the two strains. The pigmented strains created lingering abscesses. Wounds with the unpigmented strains healed quickly. These tests suggest that the staphyloxanthin may be key to the ability of S. aureus to survive immune system attacks.

Drugs designed to inhibit the bacterium's production of the staphyloxanthin may weaken it and renew its susceptibility to antibiotics.[3] In fact, because of similarities in the pathways for biosynthesis of staphyloxanthin and human cholesterol, a drug developed in the context of cholesterol-lowering therapy was shown to block S. aureus pigmentation and disease progression in a mouse infection model.[4]

Genomically, the crt operon primarily underlies the biosynthesis of staphyloxanthin;[5] however, another enzyme, AldH, found outside of the operon, was later identified as also needed for the carotenoid's production.[6] Recent comparative genomics research has further revealed that the crt operon is widespread across the Staphylococcus genus.[7] Non-aureus pigmented staphylococci have long been noted[8] and experimental support for staphyloxanthin production now exists in Staphylococcus xylosus,[9][10][11] Staphylococcus warneri,[7] Staphylococcus epidermidis[7], and Staphylococcus capitis.[12] Further, some lineages of S. aureus have been found to lack crt genes[13] and some non-aureus staphylococcal isolates have been found to feature multiple copies of crt.[7][14]

References

  1. ↑ 1.0 1.1 "Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress". Infection and Immunity 74 (8): 4950–3. August 2006. doi:10.1128/IAI.00204-06. PMID 16861688. 
  2. ↑ Campbell, Amy E.; McCready-Vangi, Amelia R.; Uberoi, Aayushi; Murga-Garrido, Sofía M.; Lovins, Victoria M.; White, Ellen K.; Pan, Jamie Ting-Chun; Knight, Simon A. B. et al. (2023-10-31). "Variable staphyloxanthin production by Staphylococcus aureus drives strain-dependent effects on diabetic wound-healing outcomes". Cell Reports 42 (10). doi:10.1016/j.celrep.2023.113281. ISSN 2211-1247. PMID 37858460. 
  3. ↑ "Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity". J Exp Med 202 (2): 209–15. 2005. doi:10.1084/jem.20050846. PMID 16009720. 
  4. ↑ "A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence". Science 319 (5868): 391–94. 2008. doi:10.1126/science.1153018. PMID 18276850. Bibcode: 2008Sci...319.1391L. 
  5. ↑ Pelz, Alexandra; Wieland, Karsten-Peter; Putzbach, Karsten; Hentschel, Petra; Albert, Klaus; Götz, Friedrich (2005-09-16). "Structure and Biosynthesis of Staphyloxanthin from Staphylococcus aureus*". Journal of Biological Chemistry 280 (37): 32493–32498. doi:10.1074/jbc.M505070200. ISSN 0021-9258. PMID 16020541. 
  6. ↑ Kim, Se Hyeuk; Lee, Pyung Cheon (2012-06-22). "Functional expression and extension of staphylococcal staphyloxanthin biosynthetic pathway in Escherichia coli". The Journal of Biological Chemistry 287 (26): 21575–21583. doi:10.1074/jbc.M112.343020. ISSN 1083-351X. PMID 22535955. 
  7. ↑ 7.0 7.1 7.2 7.3 Salamzade, Rauf; Cheong, J.Z. Alex; Sandstrom, Shelby; Swaney, Mary Hannah; Stubbendieck, Reed M.; Starr, Nicole Lane; Currie, Cameron R.; Singh, Anne Marie et al. (2023-04-28). "Evolutionary investigations of the biosynthetic diversity in the skin microbiome using lsaBGC" (in en). Microbial Genomics 9 (4). doi:10.1099/mgen.0.000988. ISSN 2057-5858. PMID 37115189. 
  8. ↑ Kloos, Wesley E.; Schleifer, Karl H. (1975). "Isolation and Characterization of Staphylococci from Human Skin II. Descriptions of Four New Species: Staphylococcus warneri, Staphylococcus capitis, Staphylococcus hominis, and Staphylococcus simulans1". International Journal of Systematic and Evolutionary Microbiology 25 (1): 62–79. doi:10.1099/00207713-25-1-62. ISSN 1466-5034. https://www.microbiologyresearch.org/content/journal/ijsem/10.1099/00207713-25-1-62. 
  9. ↑ Seel, Waldemar; Baust, Denise; Sons, Dominik; Albers, Maren; Etzbach, Lara; Fuss, Janina; Lipski, André (2020-01-15). "Carotenoids are used as regulators for membrane fluidity by Staphylococcus xylosus" (in en). Scientific Reports 10 (1): 330. doi:10.1038/s41598-019-57006-5. ISSN 2045-2322. PMID 31941915. PMC 6962212. Bibcode: 2020NatSR..10..330S. https://www.nature.com/articles/s41598-019-57006-5. 
  10. ↑ Vermassen, Aurore; Dordet-Frisoni, Emilie; de La Foye, Anne; Micheau, Pierre; Laroute, Valérie; Leroy, Sabine; Talon, Régine (2016-02-05). "Adaptation of Staphylococcus xylosus to Nutrients and Osmotic Stress in a Salted Meat Model". Frontiers in Microbiology 7: 87. doi:10.3389/fmicb.2016.00087. ISSN 1664-302X. PMID 26903967. 
  11. ↑ Cosetta, Casey M.; Niccum, Brittany; Kamkari, Nick; Dente, Michael; Podniesinski, Matthew; Wolfe, Benjamin E. (September 2023). "Bacterial-fungal interactions promote parallel evolution of global transcriptional regulators in a widespread Staphylococcus species". The ISME Journal 17 (9): 1504–1516. doi:10.1038/s41396-023-01462-5. ISSN 1751-7370. PMID 37524910. Bibcode: 2023ISMEJ..17.1504C. 
  12. ↑ Siems, Katharina; Runzheimer, Katharina; Rebrosova, Katarina; Etzbach, Lara; Auerhammer, Alina; Rehm, Anna; Schwengers, Oliver; Šiler, Martin et al. (2023-09-29). "Identification of staphyloxanthin and derivates in yellow-pigmented Staphylococcus capitis subsp. capitis" (in English). Frontiers in Microbiology 14. doi:10.3389/fmicb.2023.1272734. ISSN 1664-302X. 
  13. ↑ Holt, Deborah C.; Holden, Matthew T. G.; Tong, Steven Y. C.; Castillo-Ramirez, Santiago; Clarke, Louise; Quail, Michael A.; Currie, Bart J.; Parkhill, Julian et al. (2011). "A very early-branching Staphylococcus aureus lineage lacking the carotenoid pigment staphyloxanthin". Genome Biology and Evolution 3: 881–895. doi:10.1093/gbe/evr078. ISSN 1759-6653. PMID 21813488. 
  14. ↑ Jeong, Do-Won; Heo, Sojeong; Ryu, Sangryeol; Blom, Jochen; Lee, Jong-Hoon (2017-07-14). "Genomic insights into the virulence and salt tolerance of Staphylococcus equorum". Scientific Reports 7 (1): 5383. doi:10.1038/s41598-017-05918-5. ISSN 2045-2322. PMID 28710456. Bibcode: 2017NatSR...7.5383J. 



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