Mucin O-glycan Recycling by Akkermansia muciniphila
(2024)- Abstract
- Since time immemorial, humans have been trying to answer questions about many phenomena, especially those related to health, by creating numerous imaginary questions. One of these common questions relates to the existence of huge numbers of small organisms that live with humans, and whose number inside the human body is a thousand times greater than outside it. Today, many scientists consider all these microorganisms, together called the microbiome, to be a new organ added to the human organs, and some consider them to be a second brain because of their vital roles in human health. What makes the microbiome attractive to researchers is that it is not fully inherited from parents, it is as unique to each person as a fingerprint, it is... (More)
- Since time immemorial, humans have been trying to answer questions about many phenomena, especially those related to health, by creating numerous imaginary questions. One of these common questions relates to the existence of huge numbers of small organisms that live with humans, and whose number inside the human body is a thousand times greater than outside it. Today, many scientists consider all these microorganisms, together called the microbiome, to be a new organ added to the human organs, and some consider them to be a second brain because of their vital roles in human health. What makes the microbiome attractive to researchers is that it is not fully inherited from parents, it is as unique to each person as a fingerprint, it is flexible, and it can be modified externally via prebiotics (a non-digestible food ingredient that promotes the growth of beneficial microorganisms) and probiotics (beneficial microorganisms).
One of the challenges involved in getting the full picture and definite answers is the fact that more than 70% of the members of this organ have not been isolated and studied. What complicates matters further is the huge number of organisms in a limited space with few food sources. This makes it one of the most complex and dense biological systems on Earth.
Akkermansia muciniphila is one of the probiotics of this new proposed organ, and even a major component of up to 0.5–5% of the human microbiome. It is prevalent and to some extent abundant, and specifically inhabits the large intestine of many species. It is considered a relatively new finding, having been discovered in 2004, and is the only representative of the Verrucomicrobia family in the intestine. It is still considered a controversial and unique bacterium, not only because of its positive role in some inflammatory diseases and its flagrant offense of some neurological diseases, but also due to its amazing ability to live on the most complex of substrates: mucin, the molecule which consists of a peptide backbone decorated with O-glycan, forming a size of over 2.5MDa. Mucin is one of the largest, most diverse, and most complex proteins in the human body. As a result of the enormous complexity of the mucin molecule, the number of existing studies could be counted on our two hands.
The unique capacity to use mucins indicates that this species has unique tools (enzymes) that are capable of breaking down mucin O-glycans. This humble book was employed to study some of Akkermansia’s hypothetical enzymes. Given the fact that the O-glycans of mucin contain multiple cores, chains, different linkages, and are typically locked with α-linkages of known epitopes of histo-blood antigens, it has been believed that the enzymes that are able to break these locks represent the keys to mucin’s deconstruction and utilization, enabling the remainder of the enzymes to start their activity on the rest of the molecule.
The results revealed that Akkermansia was armored with unique enzymes, as expected. This allows it to unlock mucin as well as similar related molecules (Papers III, IV). Some of these enzymes are unique in their ability to distinguish between similar linkages, but with different chains (Papers III, IV). Moreover, the broad spectrum of activity on mucin allows the rest of the members of the gut microbiota (GM) to take advantage of some nutrients resulting from mucin recycling and degradations (Paper I). Interestingly, some results show odd behavior by revealing a dual activity of its enzymes belonging to GH109 (Paper II).
In brief, the results may be of value to bacteriologists in terms of understanding how to manipulate enzymes and the importance of those for this type of bacterium. They are also of value to researchers interested in studying mucin-like molecules from a functional point of view by shaving specific residues and studying the biological function, as well as to those interested in the recycling of related molecules. It is thus hoped that this thesis will provide some insight into the intimate relationship between A. muciniphila and mucin by bringing attention to a small portion of a much larger picture.
(Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1a3095f5-2de7-4c5f-80be-93931647a5be
- author
- SHOUKER, BASHAR LU
- supervisor
- opponent
-
- Assoc. Prof. Hägglund, Per Mårten, Copenhagen University, Denmark.
- organization
- publishing date
- 2024-01-04
- type
- Thesis
- publication status
- published
- subject
- keywords
- Mucin, Glycans, Glycoside hydrolyse, α-acting enzymes
- pages
- 75 pages
- publisher
- Department of Biotechnology, Lund University
- defense location
- Lecture Hall KC:B, Kemicentrum, Naturvetarvägen 14, Faculty of Engineering LTH, Lund University, Lund.
- defense date
- 2024-06-03 09:00:00
- ISBN
- 978-91-7422-995-0
- 978-91-7422-994-3
- language
- English
- LU publication?
- yes
- id
- 1a3095f5-2de7-4c5f-80be-93931647a5be
- date added to LUP
- 2024-05-02 16:54:07
- date last changed
- 2025-04-04 14:05:23
@phdthesis{1a3095f5-2de7-4c5f-80be-93931647a5be,
abstract = {{Since time immemorial, humans have been trying to answer questions about many phenomena, especially those related to health, by creating numerous imaginary questions. One of these common questions relates to the existence of huge numbers of small organisms that live with humans, and whose number inside the human body is a thousand times greater than outside it. Today, many scientists consider all these microorganisms, together called the microbiome, to be a new organ added to the human organs, and some consider them to be a second brain because of their vital roles in human health. What makes the microbiome attractive to researchers is that it is not fully inherited from parents, it is as unique to each person as a fingerprint, it is flexible, and it can be modified externally via prebiotics (a non-digestible food ingredient that promotes the growth of beneficial microorganisms) and probiotics (beneficial microorganisms). <br/>One of the challenges involved in getting the full picture and definite answers is the fact that more than 70% of the members of this organ have not been isolated and studied. What complicates matters further is the huge number of organisms in a limited space with few food sources. This makes it one of the most complex and dense biological systems on Earth.<br/>Akkermansia muciniphila is one of the probiotics of this new proposed organ, and even a major component of up to 0.5–5% of the human microbiome. It is prevalent and to some extent abundant, and specifically inhabits the large intestine of many species. It is considered a relatively new finding, having been discovered in 2004, and is the only representative of the Verrucomicrobia family in the intestine. It is still considered a controversial and unique bacterium, not only because of its positive role in some inflammatory diseases and its flagrant offense of some neurological diseases, but also due to its amazing ability to live on the most complex of substrates: mucin, the molecule which consists of a peptide backbone decorated with O-glycan, forming a size of over 2.5MDa. Mucin is one of the largest, most diverse, and most complex proteins in the human body. As a result of the enormous complexity of the mucin molecule, the number of existing studies could be counted on our two hands.<br/>The unique capacity to use mucins indicates that this species has unique tools (enzymes) that are capable of breaking down mucin O-glycans. This humble book was employed to study some of Akkermansia’s hypothetical enzymes. Given the fact that the O-glycans of mucin contain multiple cores, chains, different linkages, and are typically locked with α-linkages of known epitopes of histo-blood antigens, it has been believed that the enzymes that are able to break these locks represent the keys to mucin’s deconstruction and utilization, enabling the remainder of the enzymes to start their activity on the rest of the molecule.<br/>The results revealed that Akkermansia was armored with unique enzymes, as expected. This allows it to unlock mucin as well as similar related molecules (Papers III, IV). Some of these enzymes are unique in their ability to distinguish between similar linkages, but with different chains (Papers III, IV). Moreover, the broad spectrum of activity on mucin allows the rest of the members of the gut microbiota (GM) to take advantage of some nutrients resulting from mucin recycling and degradations (Paper I). Interestingly, some results show odd behavior by revealing a dual activity of its enzymes belonging to GH109 (Paper II).<br/>In brief, the results may be of value to bacteriologists in terms of understanding how to manipulate enzymes and the importance of those for this type of bacterium. They are also of value to researchers interested in studying mucin-like molecules from a functional point of view by shaving specific residues and studying the biological function, as well as to those interested in the recycling of related molecules. It is thus hoped that this thesis will provide some insight into the intimate relationship between A. muciniphila and mucin by bringing attention to a small portion of a much larger picture.<br/>}},
author = {{SHOUKER, BASHAR}},
isbn = {{978-91-7422-995-0}},
keywords = {{Mucin; Glycans; Glycoside hydrolyse; α-acting enzymes}},
language = {{eng}},
month = {{01}},
publisher = {{Department of Biotechnology, Lund University}},
school = {{Lund University}},
title = {{Mucin O-glycan Recycling by Akkermansia muciniphila}},
url = {{https://lup.lub.lu.se/search/files/182269658/Electronic_version_thesis_Bashar.pdf}},
year = {{2024}},
}