Wikipedia

Vincent Fischetti

Vincent A. Fischetti is an American microbiologist and immunologist, and Head of the Laboratory of Bacterial Pathogenesis and Immunology at Rockefeller University in New York City.

Vincent Fischetti
Born
New York
CitizenshipAmerican
Alma mater
Known for
  • Phage Lysins as antimicrobials
  • Streptococcal M protein
  • Surface proteins on gram-positive bacteria
  • LPXTG anchor motif for surface proteins
AwardsNational Institutes of Health Merit Award, 1987 & 1997
Scientific career
Institutions

He is known for pioneering the use of phage lysins as therapeutics, and for being the first scientist to clone and sequence a surface protein on gram-positive bacteria, the M protein from Streptococcus pyogenes, determining its unique coiled-coil structure.[1][2][3]

The Fischetti lab is the oldest continuous lab at Rockefeller, having been started in 1926, and was formerly headed by Homer Swift, Maclyn McCarty and Emil Gotschlich. Fischetti's primary areas of research are bacterial pathogenesis, bacterial genomics, immunology, virology, microbiology, and therapeutics.

Research and Contributions

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Fischetti became an assistant professor at Rockefeller University in 1973, an Associate Professor 1978, and a full Professor in 1990. During that time he served as the editor-in-chief of scientific journal, Infection and Immunity for 10 years and as section editor of the Journal of Immunology for 5 years.[4][5]

In 1989, the journal Science published Fischetti's research on developing a Streptococcus pyogenes vaccine using an M-protein-based approach, which was effective at preventing general streptococcal infections in a mouse model. In the 1990s, the Fischetti lab was the first to clone and sequence the M protein, making it the first surface protein on gram-positive to be cloned and sequenced. This, combined with subsequent sequence research,[a] had significant implications in vaccine development as well as streptococcal evolution.[3][6]

His lab also discovered how surface proteins are anchored in the gram-positive bacterial cell wall, identifying the LPXTG sequence motif used as the anchoring signal.[b][7] The lab discovered that this LPXTG motif was common among nearly all surface proteins on all gram-positive bacteria. This information is now critical for the development of anti-infectives and vaccines, and allows for the surface location of molecules on the bacterial cell to be predicted from sequence data. This helped lead to the identification of the anchor transpeptidase sortase by Olaf Schneewind, a former member of his lab.[8][9]

By the late 1990s, Fischetti was exploring the impact of phage lysins, a novel form of antimicrobial ammunition produced by bacterial viruses, bacteriophage, as an alternative to antibiotics, and found it to be a novel solution to target specific antibiotic resistant bacteria.[10][11][12] Other related research also explored the role of bacteriophage in disease and bacterial survival, showing that lysogenic bacteriophages are activated in vivo in the presence of a small molecule found in saliva.[13] From his work on bacteriophage, Fischetti coined the term 'phages control the biosphere' in 2018.[14]

In 2006, Fischetti was developing a lysin-based oral-nasal spray that can be delivered into the noses and mouths of hospital and nursing-home patients to prevent the impact of MRSA.[15] Tests on mice infected with MRSA found their survival rate was significantly improved.[16] One approach, a gram-negative lysin for Acinetobacter was licensed by Bioharmony Therapeutics, Inc in 2019.[17] Other lysin patents were licensed by ContraFect, who used one to control staphylococcal infections.[18]

Fischetti's work has also focused on the trigger for multiple sclerosis, and his lab alongside a lab at Weill Cornell observed that a gut-derived bacterial neurotoxin from Clostridium perfringens may be responsible for the MS trigger.[19][20]

Some of Fischetti's popular research includes is 'aged eggnog made with raw eggs is safer than drinking it fresh'.[21][22][23]

Personal life

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Fischetti grew up in West Hempstead, Long Island, NY, and enrolled at Wagner College on a pre-dental track, before majoring in bacteriology and public health.[2] He graduated in 1962, and went on to receive his master's degree in microbiology from Long Island University in 1967 whilst working at the McCarthy lab at Rockefeller. He later received his Ph.D. degree in microbiology from New York University School of Medicine in 1970 under Alan Bernheimer.[2] He later conducted postdoctoral research in the McCarty laboratory at Rockefeller University with John Zabriskie and Emil Gotschlich, focusing on streptococcal M protein, bacteriophage, and lysins.[24] After receiving a Helen Hay Whitney Foundation fellowship, Fischetti spent a year at Albert Einstein College of Medicine under Barry Bloom, working on the isolation of cytokines, before returning to the McCarty lab at Rockefeller University to continue this work on M proteins.[25] Being appointed Assistant Professor in 1974, his study of M protein was funded by the NIH for 37 years.[26]

Fischetti is known for his role as the "father" of phage lysins as therapeutics, with his laboratory being the first to use phage lysins in animal models to prevent and treat infections.[27][28][29] His studies on the M protein of Streptococcus pyogenes also revealed basic discoveries on the way surface proteins on gram-positive bacteria were anchored to the peptidoglycan.[30] These findings had critical implications for vaccine development for gram-positive pathogens including streptococci and staphylococci.

Fischetti has co-edited the ASM book Gram-Positive Pathogens, now in its 3rd edition, and Streptococcus pyogenes: Basic Biology to Clinical Manifestations, in its 2nd edition. He is also a Fellow of the New York Academy of Sciences and the National Academy of Inventors with more than 40 notable patents.

Technologies

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Fischetti has also founded several biotech spinouts from his laboratory. These include M6 Pharmaceuticals in 1994, which developed mucosal anti-infective vaccines, and was reincarnated as Siga Technologies in 1995[31] and Astoria Biologica in 2021, a company developing therapies for Multiple Sclerosis. He has also been involved in the ContraFect Corporation, a biotech started by Robert Nowinski in 2008, which licensed the Fischetti laboratory lysin technology in 2009 and developed a Staphylococcal lysin to treat MRSA.[18][32]

Notes

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  1. ^ Subsequent sequence data showed that the N-terminal region was the type-specific portion of the molecule and the C-terminal half was conserved among the many M proteins that are known. This latter information allowed for strains to be typed genetically based on the variability of the N-terminal sequence rather than the cumbersome and expensive serological typing scheme developed by Rebecca Lancefield.
  2. ^ Specifically the LPSTG signal sequence used by the transpeptidase sortase

References

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  1. ^ "Viruses Are the Antibiotics of the Future". www.vice.com. December 7, 2017. Retrieved September 27, 2022. "I think phage cocktails will have a use, but it will be a boutique treatment," Fischetti told me on the phone. "But phage cocktails are very complex and difficult to deal with, so I think lysins will be accepted before phages will only because it's a purified material and the FDA is more comfortable with that."
  2. ^ a b c "Germfighter". Wagner Magazine. December 21, 2011. Retrieved September 27, 2022.
  3. ^ a b Phillips, G N; Flicker, P F; Cohen, C; Manjula, B N; Fischetti, V A (August 1981). "Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface". Proceedings of the National Academy of Sciences. 78 (8): 4689–4693. Bibcode:1981PNAS...78.4689P. doi:10.1073/pnas.78.8.4689. ISSN 0027-8424. PMC 320228. PMID 7029524.
  4. ^ "Viruses Are the Antibiotics of the Future". www.vice.com. December 7, 2017. Retrieved September 27, 2022. Vincent Fischetti, a professor of immunology at Rockefeller University, shares Chan's skepticism about the FDA ever giving the greenlight to phage therapies. But Fischetti doesn't necessarily think this is a bad thing—in fact, he thinks he's found an even better solution.
  5. ^ "Theresa and Eugene M. Lang Center for Research and Education" (PDF).
  6. ^ Hollingshead, S K; Fischetti, V A; Scott, J R (February 1986). "Complete nucleotide sequence of type 6 M protein of the group A Streptococcus. Repetitive structure and membrane anchor". Journal of Biological Chemistry. 261 (4): 1677–1686. doi:10.1016/s0021-9258(17)35993-8. ISSN 0021-9258. PMID 3511046.
  7. ^ "Surface Proteins on Gram-Positive Bacteria". Research. Retrieved May 16, 2024.
  8. ^ "Olaf Schneewind, world-renowned authority on infectious diseases, 1961-2019 | University of Chicago News". news.uchicago.edu. May 30, 2019. Retrieved September 27, 2022. Born in Germany, Schneewind earned his bachelor of science and his degree in medicine at the University of Cologne. He came to the United States as a postdoctoral fellow at Rockefeller University, where he worked in the laboratory of bacteriology and immunology led by Vincent Fischetti.
  9. ^ Fischetti, V.A; Pancholi, V.; Schneewind, O. (September 1990). "Conservation of a hexapeptide sequence in the anchor region of surface proteins from Gram-positive cocci". Molecular Microbiology. 4 (9): 1603–1605. doi:10.1111/j.1365-2958.1990.tb02072.x. ISSN 0950-382X. PMID 2287281.
  10. ^ "Lysin therapy offers new hope for fighting drug-resistant bacteria". News. Retrieved September 27, 2022.
  11. ^ "Scientists engineer human-germ hybrid molecules to attack drug-resistant bacteria". News. Retrieved September 27, 2022.
  12. ^ Storrs, Carina. "Unearthing Anthrax's Dirty Secret: Its Mysterious Survival Skills May Rely on Help from Viruses--and Earthworms". Scientific American. Retrieved September 27, 2022. Then, four years ago, Schuch, along with Vincent Fischetti, a professor of bacteriology at Rockefeller, found a direct link—a type of phage that made anthrax resistant to an antibiotic commonly produced by other bacteria in soil, such as Streptomyces. "The remarkable thing about phages is that they expand the genetic diversity of the host that they infect," says Anca Segall, a phage biologist at San Diego State University. Segall, who calls Schuch and Fischetti's work to uncover the role of new anthracis phages "absolutely spectacular," started sequencing the DNA of phages from marine Bacilli several years ago. Some of the viruses she found induce the aquatic bacteria to sporulate.
  13. ^ Broudy, Thomas B.; Fischetti, Vincent A. (July 2003). "In Vivo Lysogenic Conversion of Tox − Streptococcus pyogenes to Tox + with Lysogenic Streptococci or Free Phage". Infection and Immunity. 71 (7): 3782–3786. doi:10.1128/IAI.71.7.3782-3786.2003. ISSN 0019-9567. PMC 161974. PMID 12819060.
  14. ^ Fischetti, Vincent A. (June 2018). "Development of Phage Lysins as Novel Therapeutics: A Historical Perspective". Viruses. 10 (6): 310. doi:10.3390/v10060310. ISSN 1999-4915. PMC 6024357. PMID 29875339.
  15. ^ Vaisman, Daria (May 30, 2006). "The Soviet method for attacking infection". Slate Magazine. Retrieved September 27, 2022. Vincent Fischetti, a professor at the Rockefeller Institute, is designing a phage-based enzyme solution that can be sprayed into the noses and mouths of hospital and nursing-home patients. Fischetti and researchers in Tbilisi are also experimenting with using phages to detect anthrax and cholera in the case of a terrorist attack.
  16. ^ "Human-virus hybrid created to kill off MRSA superbug". The Independent. April 17, 2017. Retrieved September 27, 2022. One of the researchers, Professor Vincent Fischetti, of The Rockefeller University in the US, said: "Bacteria-infecting viruses have molecules that recognize and tightly bind to these common components of the bacterial cell's surface that the human immune system largely misses.
  17. ^ "Bioharmony Therapeutics and Boehringer Ingelheim Collaborate to Advance Bacteriophage Lysin Therapeutics for the Treatment of Multi-Drug Resistant Bacterial Infections". www.businesswire.com. January 15, 2019. Retrieved September 27, 2022. NEW YORK--(BUSINESS WIRE)--Bioharmony Therapeutics, Inc. ("Bioharmony"), a biopharmaceutical company focusing on the development of novel therapeutics for hard to treat bacterial infections, announced today that it has entered into a Collaborative Research and Licensing Agreement with Boehringer Ingelheim to develop bacteriophage lysins for the treatment of multidrug resistant (MDR) Acinetobacter infections, a frequent cause of hospital-acquired pneumonia and life-threatening blood or wound infections. Bioharmony licensed this technology from the Rockefeller University. The discoveries are from the laboratory of Vincent A. Fischetti, Ph.D., a faculty member at The Rockefeller University.
  18. ^ a b Borrell, Brendan (August 1, 2012). "Could Bacteria-Fighting Viruses Replace Overused Antibiotics?". Scientific American. Retrieved May 16, 2024.
  19. ^ Ma, Yinghua; Sannino, David; Linden, Jennifer R.; Haigh, Sylvia; Zhao, Baohua; Grigg, John B.; Zumbo, Paul; Dündar, Friederike; Butler, Daniel; Profaci, Caterina P.; Telesford, Kiel; Winokur, Paige N.; Rumah, Kareem R.; Gauthier, Susan A.; Fischetti, Vincent A. (May 1, 2023). "Epsilon toxin–producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege". The Journal of Clinical Investigation. 133 (9). doi:10.1172/JCI163239. ISSN 0021-9738. PMC 10145940. PMID 36853799.
  20. ^ Bekiempis, Victoria (October 17, 2013). "Multiple Sclerosis Research Points a Finger at Bacteria". Newsweek. Retrieved September 27, 2022.
  21. ^ "Homemade Eggnog Can Kill Salmonella with Booze". ABC News. Retrieved September 27, 2022.
  22. ^ Arumugam, Nadia. "Why Aged Eggnog Made With Raw Eggs Is Safer Than Drinking It Fresh". Forbes. Retrieved September 27, 2022. Determined to prove, or at least demonstrate with authority, that the copious amount of alcohol in a single batch of the Lancefield recipe (1 pint of Bourbon and 1 quart of rum) is capable of annihilating any salmonella present in the raw egg eggnog after the ageing process, the lab head, Professor Vincent Fischetti, conducted a rudimentary experiment.
  23. ^ Ragusea, Adam (November 28, 2022). "AGE your raw egg eggnog". Youtube.
  24. ^ Abdelrahman, F.; Easwaran, M.; Daramola, O. I.; Ragab, S.; Lynch, S.; Oduselu, T. J.; Khan, F. M.; Ayobami, A.; Adnan, F.; Torrents, E.; Sanmukh, S.; El-Shibiny, A. (February 10, 2021). "Phage-Encoded Endolysins". Antibiotics. 10 (2): 124. doi:10.3390/antibiotics10020124. PMC 7912344. PMID 33525684. prepared a highly purified C1 lysin as a resolution of his thesis work at the McCarthy laboratory and this allowed for further detailed studies on how surface proteins of Gram-positive organisms bind to the cell wall
  25. ^ "The Rockefeller University » Laboratory of Bacterial Pathogenesis and Immunology". lab.rockefeller.edu. Retrieved May 16, 2024.
  26. ^ "The Rockefeller University » Laboratory of Bacterial Pathogenesis and Immunology". lab.rockefeller.edu. Retrieved September 27, 2022.
  27. ^ "Boon Chong Goh on LinkedIn: Incredibly honored to meet the father of phage lysins - Professor Vincent…". www.linkedin.com. Retrieved May 20, 2024.
  28. ^ PhD, Julianna LeMieux (August 3, 2020). "Lysins Unlimited: Phages' Secret Weapon". GEN - Genetic Engineering and Biotechnology News. Retrieved May 16, 2024. Vincent A. Fischetti, PhD, the primary developer of the lysin technology, has been on the faculty at the Rockefeller University since 1973. He purified a phage lysin during his thesis work, using it to extract proteins from group A streptococci. Fast forward to the year 2000, Fischetti was, he recalls, 'the right person at the right time.' He added lysin to the throats of mice that had been colonized with streptococcal bacteria. The bacteria died, and the idea to use lysins as a therapeutic was born. Fischetti obtained a broad patent, received two grants from the Defense Advanced Research Projects Agency select DARPA union and published a string of papers.
  29. ^ "The Rockefeller University » Hospital Centennial". centennial.rucares.org. Retrieved May 16, 2024.
  30. ^ Vollmer, Waldemar; Blanot, Didier; De Pedro, Miguel A. (2008). "Peptidoglycan structure and architecture". FEMS Microbiology Reviews. 32 (2): 149–167. doi:10.1111/j.1574-6976.2007.00094.x. PMID 18194336.
  31. ^ "SEC Filing". Dr. Vincent Fischetti, the principal founding scientist of the Company's technologies, at an exercise price of $1.50 per share (the "Fischetti Warrants")
  32. ^ Lopatto, Elizabeth (October 10, 2012). "Good Viruses Will Fight Acne as 1915 Discovery Revived: Health". Bloomberg News. Retrieved May 16, 2024.
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