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Center for Research and Education |url=https://www.nyp.org/documents/queens/lang-center/researchday-speaker-2006.pdf}}</ref>
Center for Research and Education |url=https://www.nyp.org/documents/queens/lang-center/researchday-speaker-2006.pdf}}</ref>


In 1989, the journal [[Science (journal)|''Science'']] published Fischetti's research on developing a [[Streptococcus|Streptococcus pyogenes vaccine]] using an M-protein-based approach, which had been effective at preventing general streptococcal infections in mice. His lab also discovered that surface proteins are anchored in the bacterial cell wall, identifying the sequence used as the anchoring signal.{{efn|Specifically the LPSTG signal sequence used by the transpeptidase sortase}}<ref>{{Cite web |title=Surface Proteins on Gram-Positive Bacteria |url=https://www.rockefeller.edu/research/fischetti-laboratory/195207-surface-proteins/ |access-date=2024-05-16 |website=Research |language=en}}</ref> By the late 1990s, he was exploring the impact of phage lysins, a novel form of [[antimicrobial]] ammunition, as an alternative to [[antibiotic]]s, and found it to be a novel solution to target specific antibiotic resistant bacteria.<ref>{{Cite web |title=Lysin therapy offers new hope for fighting drug-resistant bacteria |url=https://www.rockefeller.edu/news/24920-lysin-therapy-offers-new-hope-fighting-drug-resistant-bacteria/ |access-date=2022-09-27 |website=News |language=en}}</ref><ref>{{Cite web |title=Scientists engineer human-germ hybrid molecules to attack drug-resistant bacteria |url=https://www.rockefeller.edu/news/19180-scientists-engineer-human-germ-hybrid-molecules-attack-drug-resistant-bacteria/ |access-date=2022-09-27 |website=News |language=en}}</ref><ref>{{Cite web |last=Storrs |first=Carina |title=Unearthing Anthrax's Dirty Secret: Its Mysterious Survival Skills May Rely on Help from Viruses--and Earthworms |url=https://www.scientificamerican.com/article/anthrax-soil/ |access-date=2022-09-27 |website=Scientific American |language=en |quote=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.}}</ref> 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 [[Methicillin-resistant Staphylococcus aureus|MRSA]].<ref>{{Cite web |last=Vaisman |first=Daria |date=2006-05-30 |title=The Soviet method for attacking infection. |url=https://slate.com/technology/2006/05/the-soviet-method-for-attacking-infection.html |access-date=2022-09-27 |website=Slate Magazine |language=en |quote=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.}}</ref> Tests on mice infected with [[Methicillin-resistant Staphylococcus aureus|MRSA]] found their survival rate was significantly improved, leading to the commencement of human testing in 2017.<ref>{{Cite web |date=2017-04-17 |title=Human-virus hybrid created to kill off MRSA superbug |url=https://www.independent.co.uk/news/science/human-virus-hybrid-bacteria-infection-mrsa-immune-system-rockefeller-university-a7686916.html |access-date=2022-09-27 |website=The Independent |language=en |quote=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.}}</ref> These tests have 'near 40 patents'  and one approach was licensed by Bioharmony Therapeutics, Inc in 2019.<ref>{{Cite web |date=2019-01-15 |title=Bioharmony Therapeutics and Boehringer Ingelheim Collaborate to Advance Bacteriophage Lysin Therapeutics for the Treatment of Multi-Drug Resistant Bacterial Infections |url=https://www.businesswire.com/news/home/20190115005244/en/Bioharmony-Therapeutics-and-Boehringer-Ingelheim-Collaborate-to-Advance-Bacteriophage-Lysin-Therapeutics-for-the-Treatment-of-Multi-Drug-Resistant-Bacterial-Infections |access-date=2022-09-27 |website=www.businesswire.com |language=en |quote=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.}}</ref> Other lysin patents were licensed by ContraFect.<ref>{{Cite web |last=Borrell |first=Brendan |date=2012-08-01 |title=Could Bacteria-Fighting Viruses Replace Overused Antibiotics? |url=https://www.scientificamerican.com/article/could-bacteria-fighting-viruses-replace-antibiotics/ |access-date=2024-05-16 |website=Scientific American |language=en}}</ref>
In 1989, the journal [[Science (journal)|''Science'']] published Fischetti's research on developing a [[Streptococcus|Streptococcus pyogenes vaccine]] using an M-protein-based approach, which had been effective at preventing general streptococcal infections in mice. His lab also discovered that surface proteins are anchored in the bacterial cell wall, identifying the sequence used as the anchoring signal.{{efn|Specifically the LPSTG signal sequence used by the transpeptidase sortase}}<ref>{{Cite web |title=Surface Proteins on Gram-Positive Bacteria |url=https://www.rockefeller.edu/research/fischetti-laboratory/195207-surface-proteins/ |access-date=2024-05-16 |website=Research |language=en}}</ref> 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,{{efn|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.}} had significant implications in vaccine development as well as streptococcal evolution.<ref>{{Cite journal |last=Phillips |first=G N |last2=Flicker |first2=P F |last3=Cohen |first3=C |last4=Manjula |first4=B N |last5=Fischetti |first5=V A |date=1981-08 |title=Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. |url=https://pnas.org/doi/full/10.1073/pnas.78.8.4689 |journal=Proceedings of the National Academy of Sciences |language=en |volume=78 |issue=8 |pages=4689–4693 |doi=10.1073/pnas.78.8.4689 |issn=0027-8424}}</ref><ref>{{Cite journal |last=Hollingshead |first=S K |last2=Fischetti |first2=V A |last3=Scott |first3=J R |date=1986-02 |title=Complete nucleotide sequence of type 6 M protein of the group A Streptococcus. Repetitive structure and membrane anchor. |url=https://doi.org/10.1016/S0021-9258(17)35993-8 |journal=Journal of Biological Chemistry |volume=261 |issue=4 |pages=1677–1686 |doi=10.1016/s0021-9258(17)35993-8 |issn=0021-9258}}</ref> The lab also identified a motif, [[LPXTGase|LPXTG]], that was common among nearly all surface proteins on gram-positive bacteria, showing that this motif was an anchoring signal for surface proteins on gram-positive bacteria. This information is now critical for the development of anti-infectives and vaccines, and allows for the surface location of molecules in the bacterial cell can be predicted, leading to the identification of [[sortase]].<ref>{{Cite journal |last=Fischetti |first=V.A |last2=Pancholi |first2=V. |last3=Schneewind |first3=O. |date=1990-09 |title=Conservation of a hexapeptide sequence in the anchor region of surface proteins from Gram‐positive cocci |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.1990.tb02072.x |journal=Molecular Microbiology |language=en |volume=4 |issue=9 |pages=1603–1605 |doi=10.1111/j.1365-2958.1990.tb02072.x |issn=0950-382X}}</ref>
By the late 1990s, he was exploring the impact of phage lysins, a novel form of [[antimicrobial]] ammunition, as an alternative to [[antibiotic]]s, and found it to be a novel solution to target specific antibiotic resistant bacteria.<ref>{{Cite web |title=Lysin therapy offers new hope for fighting drug-resistant bacteria |url=https://www.rockefeller.edu/news/24920-lysin-therapy-offers-new-hope-fighting-drug-resistant-bacteria/ |access-date=2022-09-27 |website=News |language=en}}</ref><ref>{{Cite web |title=Scientists engineer human-germ hybrid molecules to attack drug-resistant bacteria |url=https://www.rockefeller.edu/news/19180-scientists-engineer-human-germ-hybrid-molecules-attack-drug-resistant-bacteria/ |access-date=2022-09-27 |website=News |language=en}}</ref><ref>{{Cite web |last=Storrs |first=Carina |title=Unearthing Anthrax's Dirty Secret: Its Mysterious Survival Skills May Rely on Help from Viruses--and Earthworms |url=https://www.scientificamerican.com/article/anthrax-soil/ |access-date=2022-09-27 |website=Scientific American |language=en |quote=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.}}</ref> Other 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.<ref>{{Cite journal |last=Broudy |first=Thomas B. |last2=Fischetti |first2=Vincent A. |date=2003-07 |title=In Vivo Lysogenic Conversion of Tox − Streptococcus pyogenes to Tox + with Lysogenic Streptococci or Free Phage |url=https://journals.asm.org/doi/10.1128/IAI.71.7.3782-3786.2003 |journal=Infection and Immunity |language=en |volume=71 |issue=7 |pages=3782–3786 |doi=10.1128/IAI.71.7.3782-3786.2003 |issn=0019-9567 |pmc=PMC161974 |pmid=12819060}}</ref> 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 [[Methicillin-resistant Staphylococcus aureus|MRSA]].<ref>{{Cite web |last=Vaisman |first=Daria |date=2006-05-30 |title=The Soviet method for attacking infection. |url=https://slate.com/technology/2006/05/the-soviet-method-for-attacking-infection.html |access-date=2022-09-27 |website=Slate Magazine |language=en |quote=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.}}</ref> Tests on mice infected with [[Methicillin-resistant Staphylococcus aureus|MRSA]] found their survival rate was significantly improved, leading to the commencement of human testing in 2017.<ref>{{Cite web |date=2017-04-17 |title=Human-virus hybrid created to kill off MRSA superbug |url=https://www.independent.co.uk/news/science/human-virus-hybrid-bacteria-infection-mrsa-immune-system-rockefeller-university-a7686916.html |access-date=2022-09-27 |website=The Independent |language=en |quote=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.}}</ref> These tests have 'near 40 patents'  and one approach was licensed by Bioharmony Therapeutics, Inc in 2019.<ref>{{Cite web |date=2019-01-15 |title=Bioharmony Therapeutics and Boehringer Ingelheim Collaborate to Advance Bacteriophage Lysin Therapeutics for the Treatment of Multi-Drug Resistant Bacterial Infections |url=https://www.businesswire.com/news/home/20190115005244/en/Bioharmony-Therapeutics-and-Boehringer-Ingelheim-Collaborate-to-Advance-Bacteriophage-Lysin-Therapeutics-for-the-Treatment-of-Multi-Drug-Resistant-Bacterial-Infections |access-date=2022-09-27 |website=www.businesswire.com |language=en |quote=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.}}</ref> Other lysin patents were licensed by ContraFect.<ref>{{Cite web |last=Borrell |first=Brendan |date=2012-08-01 |title=Could Bacteria-Fighting Viruses Replace Overused Antibiotics? |url=https://www.scientificamerican.com/article/could-bacteria-fighting-viruses-replace-antibiotics/ |access-date=2024-05-16 |website=Scientific American |language=en}}</ref>

Fischetti's work has also focused on the trigger for [[multiple sclerosis]], and his lab alongside [[Weill Cornell Medicine|Weill Cornell]] observed that a gut-derived bacterial [[neurotoxin]] may be responsible for the MS trigger.<ref>{{Cite journal |last=Ma |first=Yinghua |last2=Sannino |first2=David |last3=Linden |first3=Jennifer R. |last4=Haigh |first4=Sylvia |last5=Zhao |first5=Baohua |last6=Grigg |first6=John B. |last7=Zumbo |first7=Paul |last8=Dündar |first8=Friederike |last9=Butler |first9=Daniel |last10=Profaci |first10=Caterina P. |last11=Telesford |first11=Kiel |last12=Winokur |first12=Paige N. |last13=Rumah |first13=Kareem R. |last14=Gauthier |first14=Susan A. |last15=Fischetti |first15=Vincent A. |date=2023-05-01 |title=Epsilon toxin–producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege |url=https://www.jci.org/articles/view/163239 |journal=The Journal of Clinical Investigation |language=en |volume=133 |issue=9 |doi=10.1172/JCI163239 |issn=0021-9738}}</ref>


His postdoctoral students include microbiologist [[Olaf Schneewind]], who identified [[sortase]] after leaving the Fischetti lab.<ref>{{Cite web |title=Olaf Schneewind, world-renowned authority on infectious diseases, 1961-2019 {{!}} University of Chicago News |url=https://news.uchicago.edu/story/olaf-schneewind-world-renowned-authority-infectious-diseases-1961-2019 |access-date=2022-09-27 |website=news.uchicago.edu |date=30 May 2019 |language=en |quote=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.}}</ref> Some of Fischetti's popular research includes is 'aged eggnog made with raw eggs is safer than drinking it fresh'.<ref>{{Cite web |title=Homemade Eggnog Can Kill Salmonella with Booze |url=https://abcnews.go.com/Health/holiday-miracle-homemade-eggnog-kills-salmonella-booze/story?id=17905639 |access-date=2022-09-27 |website=ABC News |language=en}}</ref><ref>{{Cite web |last=Arumugam |first=Nadia |title=Why Aged Eggnog Made With Raw Eggs Is Safer Than Drinking It Fresh |url=https://www.forbes.com/sites/nadiaarumugam/2013/12/20/why-aged-eggnog-made-with-raw-eggs-is-safer-than-drinking-it-fresh/ |access-date=2022-09-27 |website=Forbes |language=en |quote=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.}}</ref><ref>{{Cite web |last=Bekiempis |first=Victoria |date=2013-10-17 |title=Multiple Sclerosis Research Points a Finger at Bacteria |url=https://www.newsweek.com/multiple-sclerosis-research-points-finger-bacteria-450 |access-date=2022-09-27 |website=Newsweek |language=en}}</ref><ref>{{Cite web |last=Ragusea |first=Adam |date=28 Nov 2022 |title=AGE your raw egg eggnog |url=https://www.youtube.com/watch?v=sflZWeCjdco |website=Youtube}}</ref>
His postdoctoral students include microbiologist [[Olaf Schneewind]], who identified [[sortase]] after leaving the Fischetti lab.<ref>{{Cite web |title=Olaf Schneewind, world-renowned authority on infectious diseases, 1961-2019 {{!}} University of Chicago News |url=https://news.uchicago.edu/story/olaf-schneewind-world-renowned-authority-infectious-diseases-1961-2019 |access-date=2022-09-27 |website=news.uchicago.edu |date=30 May 2019 |language=en |quote=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.}}</ref> Some of Fischetti's popular research includes is 'aged eggnog made with raw eggs is safer than drinking it fresh'.<ref>{{Cite web |title=Homemade Eggnog Can Kill Salmonella with Booze |url=https://abcnews.go.com/Health/holiday-miracle-homemade-eggnog-kills-salmonella-booze/story?id=17905639 |access-date=2022-09-27 |website=ABC News |language=en}}</ref><ref>{{Cite web |last=Arumugam |first=Nadia |title=Why Aged Eggnog Made With Raw Eggs Is Safer Than Drinking It Fresh |url=https://www.forbes.com/sites/nadiaarumugam/2013/12/20/why-aged-eggnog-made-with-raw-eggs-is-safer-than-drinking-it-fresh/ |access-date=2022-09-27 |website=Forbes |language=en |quote=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.}}</ref><ref>{{Cite web |last=Bekiempis |first=Victoria |date=2013-10-17 |title=Multiple Sclerosis Research Points a Finger at Bacteria |url=https://www.newsweek.com/multiple-sclerosis-research-points-finger-bacteria-450 |access-date=2022-09-27 |website=Newsweek |language=en}}</ref><ref>{{Cite web |last=Ragusea |first=Adam |date=28 Nov 2022 |title=AGE your raw egg eggnog |url=https://www.youtube.com/watch?v=sflZWeCjdco |website=Youtube}}</ref>
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Fischetti has also published the [[American Society for Microbiology|ASM]] book Gram-Positive Pathogens, now in its 3rd edition. He is also a Fellow of the [[New York Academy of Sciences]].
Fischetti has also published the [[American Society for Microbiology|ASM]] book Gram-Positive Pathogens, now in its 3rd edition. He is also a Fellow of the [[New York Academy of Sciences]].

== Major Contributions to Science ==

1. '''The Coiled Coil Structure of Streptococcal M Protein'''. His lab was the first to clone and then sequence the M protein making it the first surface protein on gram-positive to be cloned and sequenced. As such, the M protein was the archetypical molecule for surface proteins on gram-positive organisms. The Protein A sequence was published just before the M protein but there was a sequencing error near the C terminus that was corrected after the M protein sequence was published. 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]]. All this information about the M molecule had significant implications in vaccine development as well as streptococcal evolution. (https://doi.org/10.1073/pnas.78.8.4689)( https://doi.org/10.1016/S0021-9258(17)35993-8 )

2. '''Surface Protein Anchoring in Gram-Positive Pathogens'''. The Fischetti lab identified a motif (LPXTG) that was common among nearly all surface proteins on gram-positive bacteria. It was later proved that this motif was an anchoring signal for surface proteins on gram-positive bacteria. This information is now critical for the development of anti-infectives and vaccines. Also, by searching the bacterial sequence database for molecules with an LPXTG motif close to their C-terminii, the surface location of the molecules in the bacterial cell can be predicted. This finding lead to the identification of sortase, the transpeptidase responsible for the anchoring process. Inhibition of sortase activity by a small molecule can render the organism non-virulent and easily cleared by the immune system. (https://doi.org/10.1111/j.1365-2958.1990.tb02072.x)

3. '''Identification of Biologically Active Surface Proteins on S. pyogenes'''. Other than M protein, not much was known about the surface proteins on S. pyogenes that may be important in their pathogenesis. The Fischetti lab systematically identified several important molecules that could play a role in their pathogenesis and the antiphagocytic activity of the M protein. An important group of molecules were five contiguous glycolytic enzymes that are normally found in the cytoplasm but are located on the cell surface in a complex with the ability to produce ATP. Many of these same molecules are located on other pathogens such as S. aureus, S. pneumoniae, Candida and Trypanosomes and reported to be associated with autoimmune diseases. (https://doi.org/10.1084/jem.176.2.415)

4. '''Role of Bacteriophage in Disease and Bacterial Survival'''. Bacteriophages are prevalent in the environment and from bacterial genome sequence, it appears that they are also common inhabitants of nearly all bacteria. However, while phage carry virulence determinants on their genomes, their role in pathogenesis was poorly understood. For the first time the Fischetti lab showed that lysogenic bacteriophages are activated in vivo in the presence of a small molecule found in saliva. This implies that lysogenic phage could sense their environment and mobilize themselves or molecules for their survival. This is clearly seen in B. anthracis, where it was shown that when vegetative organisms enter the soil, they become lysogenized by soil phage, converting them to free living organisms able to survive in the soil. They also found that while lysogeny is defined as phage incorporation in the bacterial host DNA, there is a prevalence of plasmodial phage in the cytoplasm of pathogens (particularly B. anthracis and S. aureus) that contain virulence determinants that would be missed during normal bacterial genome sequencing. Thus, the Fischetti lab has identified a potential reservoir of virulence genes that have not been previously considered.(https://doi.org/10.1128/iai.71.7.3782-3786.2003)

5. '''Lysins as Novel Therapeutics'''. Given the increase in antibiotic resistance by pathogenic bacteria, new methods must be devised to control these pathogens. The Fischetti laboratory was the first to perform experiments to determine if phage lysins may be used therapeutically. Mice orally colonized with S. pyogenes were subsequently treated with one dose of lysin orally. After treatment, the mice were found to be decolonized of their streptococci. This was the first publication describing the therapeutic effects of phage lysins. During the ensuing years, the Fischetti laboratory developed phage lysins against all of the major gram-positive pathogens and now have lysins against both gram-negative pathogens, including the ESKAPE pathogens. A staphylococcal-specific lysin that the Fischetti lab developed is currently in phase 3 human clinical trials and if successful, could be the turning point for the widespread therapeutic use of lysins. (https://doi.org/10.1073/pnas.061038398) (https://doi.org/10.1016/j.tim.2005.08.007).

6. '''Lysibodies''': Engineered Immunoglobulins to Control S. aureus. The cell wall of Gram-positive bacteria contains abundant surface-exposed carbohydrate structures that are highly conserved. While these properties make surface carbohydrates ideal targets for immunotherapy, carbohydrates elicit a notoriously poor immune response. The Fischetti lab has been successful in engineering a hybrid IgG molecule called a “Lysibody” that is a human IgG1 directed to carbohydrate epitopes in the bacterial cell wall. Lysibodies are engineered immunoglobulin, combining in a single molecule a high-affinity carbohydrate-binding domain from enzymes of bacterial or bacteriophage origin (the Fab), and the Fc effector portion of human IgG1, forming a hybrid immunoglobulin with all the effector functions of normal human IgG. Currently, there are no vaccines or immunoglobulins against S. aureus since most antibodies are directed to protein targets that can vary among different strains, and their expression is also variable. A lysibody directed against methicillin resistant Staphylococcus aureus (MRSA) is currently in pre-clinical development to be used as prophylaxis in pre-surgical and dialysis patients and neonates to prevent MRSA and other staphylococcal infections.(https://doi.org/10.1073/pnas.1619249114)

7. '''The Trigger for Multiple Sclerosis'''. Multiple Sclerosis (MS) is a serious neurological disease that often affects young adults. Despite its impact on human health, the cause of this disease remains unknown. Over the past decade, Fischetti lab members (particularly Rashid Rumah) and their collaborators at Weill Cornell made a groundbreaking discovery, linking a gut-derived bacterial [[neurotoxin]], called epsilon toxin (ETX), to MS. ETX is produced by the gut bacterium, Clostridium perfringens, and may be responsible for the MS trigger. In early 2023, we published a seminal paper in JCI (https://doi.org/10.1172/JCI163239) showing that ETX-producing C. perfringens bacteria could be identified in the intestines of 61% of MS patients compared to 13% of healthy individuals. Furthermore, MS patients who were ETX positive carried 1,500-fold more C. perfringens in their intestines than healthy individuals who were asymptomatic carriers. Lastly, we showed that ETX triggers MS-like brain lesions in experimental rodents that better approximate the regional brain distribution of human MS lesions, compared to more traditional animal models of MS. This agrees with earlier work where we showed that ETX binds to and damages both the blood brain barrier and brain myelin, further linking ETX to MS.(https://doi.org/10.1172/JCI163239) (https://doi.org/10.1371/journal.pone.0076359)


== Technologies ==
== Technologies ==

Revision as of 15:48, 16 May 2024

Vincent Fischetti
BornOctober 1940
New York
CitizenshipAmerican
Alma mater
Known for
  • Phage Lysins as antimicrobials
  • Streptococcal M protein
  • Surface proteins on gram-positive bacteria
AwardsNational Institutes of Health Merit Award, 1987 & 1997
Scientific career
Institutions

Vincent A. Fischetti (born 1940) is an American microbiologist and immunologist, and Head of the Laboratory of Bacterial Pathogenesis and Immunology at Rockefeller University in New York City.

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

The Fischetti lab is the oldest 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

Fischetti became an assistant professor at Rockefeller University in 1973, an Associate Professor 1978, and a full Professor in 1990. He later 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.[3][4]

In 1989, the journal Science published Fischetti's research on developing a Streptococcus pyogenes vaccine using an M-protein-based approach, which had been effective at preventing general streptococcal infections in mice. His lab also discovered that surface proteins are anchored in the bacterial cell wall, identifying the sequence used as the anchoring signal.[a][5] 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,[b] had significant implications in vaccine development as well as streptococcal evolution.[6][7] The lab also identified a motif, LPXTG, that was common among nearly all surface proteins on gram-positive bacteria, showing that this motif was an anchoring signal for surface proteins on gram-positive bacteria. This information is now critical for the development of anti-infectives and vaccines, and allows for the surface location of molecules in the bacterial cell can be predicted, leading to the identification of sortase.[8]

By the late 1990s, he was exploring the impact of phage lysins, a novel form of antimicrobial ammunition, as an alternative to antibiotics, and found it to be a novel solution to target specific antibiotic resistant bacteria.[9][10][11] Other 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.[12] 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.[13] Tests on mice infected with MRSA found their survival rate was significantly improved, leading to the commencement of human testing in 2017.[14] These tests have 'near 40 patents'  and one approach was licensed by Bioharmony Therapeutics, Inc in 2019.[15] Other lysin patents were licensed by ContraFect.[16]

Fischetti's work has also focused on the trigger for multiple sclerosis, and his lab alongside Weill Cornell observed that a gut-derived bacterial neurotoxin may be responsible for the MS trigger.[17]

His postdoctoral students include microbiologist Olaf Schneewind, who identified sortase after leaving the Fischetti lab.[18] Some of Fischetti's popular research includes is 'aged eggnog made with raw eggs is safer than drinking it fresh'.[19][20][21][22]

Personal life

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 and a 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, focussing on lysins.[23] 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 work on M proteins.[24] Being appointed Assistant Professor in 1974, his study of M protein was funded for 37 years.[25]

Fischetti is known for his role as the primary developer of the use of phage lysins, with his laboratory being the first to use phage lysins as therapeutics.[26][27] 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.[28] These findings had critical implications for vaccine development for gram-positive pathogens including streptococci.

Fischetti has also published the ASM book Gram-Positive Pathogens, now in its 3rd edition. He is also a Fellow of the New York Academy of Sciences.

Technologies

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.[29] Others include 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.[30][31]

References

  1. ^ "Viruses Are the Antibiotics of the Future". www.vice.com. 7 December 2017. Retrieved 2022-09-27. "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. 2011-12-21. Retrieved 2022-09-27.
  3. ^ "Viruses Are the Antibiotics of the Future". www.vice.com. 7 December 2017. Retrieved 2022-09-27. 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.
  4. ^ "Theresa and Eugene M. Lang Center for Research and Education" (PDF). {{cite web}}: line feed character in |title= at position 27 (help)
  5. ^ "Surface Proteins on Gram-Positive Bacteria". Research. Retrieved 2024-05-16.
  6. ^ Phillips, G N; Flicker, P F; Cohen, C; Manjula, B N; Fischetti, V A (1981-08). "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. doi:10.1073/pnas.78.8.4689. ISSN 0027-8424. {{cite journal}}: Check date values in: |date= (help)
  7. ^ Hollingshead, S K; Fischetti, V A; Scott, J R (1986-02). "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. {{cite journal}}: Check date values in: |date= (help)
  8. ^ Fischetti, V.A; Pancholi, V.; Schneewind, O. (1990-09). "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. {{cite journal}}: Check date values in: |date= (help)
  9. ^ "Lysin therapy offers new hope for fighting drug-resistant bacteria". News. Retrieved 2022-09-27.
  10. ^ "Scientists engineer human-germ hybrid molecules to attack drug-resistant bacteria". News. Retrieved 2022-09-27.
  11. ^ Storrs, Carina. "Unearthing Anthrax's Dirty Secret: Its Mysterious Survival Skills May Rely on Help from Viruses--and Earthworms". Scientific American. Retrieved 2022-09-27. 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.
  12. ^ Broudy, Thomas B.; Fischetti, Vincent A. (2003-07). "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. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  13. ^ Vaisman, Daria (2006-05-30). "The Soviet method for attacking infection". Slate Magazine. Retrieved 2022-09-27. 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.
  14. ^ "Human-virus hybrid created to kill off MRSA superbug". The Independent. 2017-04-17. Retrieved 2022-09-27. 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.
  15. ^ "Bioharmony Therapeutics and Boehringer Ingelheim Collaborate to Advance Bacteriophage Lysin Therapeutics for the Treatment of Multi-Drug Resistant Bacterial Infections". www.businesswire.com. 2019-01-15. Retrieved 2022-09-27. 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.
  16. ^ Borrell, Brendan (2012-08-01). "Could Bacteria-Fighting Viruses Replace Overused Antibiotics?". Scientific American. Retrieved 2024-05-16.
  17. ^ 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. (2023-05-01). "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.
  18. ^ "Olaf Schneewind, world-renowned authority on infectious diseases, 1961-2019 | University of Chicago News". news.uchicago.edu. 30 May 2019. Retrieved 2022-09-27. 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.
  19. ^ "Homemade Eggnog Can Kill Salmonella with Booze". ABC News. Retrieved 2022-09-27.
  20. ^ Arumugam, Nadia. "Why Aged Eggnog Made With Raw Eggs Is Safer Than Drinking It Fresh". Forbes. Retrieved 2022-09-27. 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.
  21. ^ Bekiempis, Victoria (2013-10-17). "Multiple Sclerosis Research Points a Finger at Bacteria". Newsweek. Retrieved 2022-09-27.
  22. ^ Ragusea, Adam (28 Nov 2022). "AGE your raw egg eggnog". Youtube.
  23. ^ "Phage-Encoded Endolysins". Antibiotics (Basel). 10 Feb 2021. 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
  24. ^ "The Rockefeller University » Laboratory of Bacterial Pathogenesis and Immunology". lab.rockefeller.edu. Retrieved 2024-05-16.
  25. ^ "The Rockefeller University » Laboratory of Bacterial Pathogenesis and Immunology". lab.rockefeller.edu. Retrieved 2022-09-27.
  26. ^ PhD, Julianna LeMieux (2020-08-03). "Lysins Unlimited: Phages' Secret Weapon". GEN - Genetic Engineering and Biotechnology News. Retrieved 2024-05-16. 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.
  27. ^ "The Rockefeller University » Hospital Centennial". centennial.rucares.org. Retrieved 2024-05-16.
  28. ^ academic.oup.com https://academic.oup.com/femsre/article/32/2/149/2683904. Retrieved 2024-05-16. {{cite web}}: Missing or empty |title= (help)
  29. ^ "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") {{cite web}}: line feed character in |quote= at position 46 (help)
  30. ^ Borrell, Brendan (2012-08-01). "Could Bacteria-Fighting Viruses Replace Overused Antibiotics?". Scientific American. Retrieved 2024-05-16.
  31. ^ "Bloomberg - Are you a robot?". www.bloomberg.com. Retrieved 2024-05-16. {{cite web}}: Cite uses generic title (help)


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