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Studies on Haemproteins of Gram-positive Bacteria - Implications as Antibacterial Drug Targets

Kjelgaard, Peter LU (2007)
Abstract (Swedish)
Popular Abstract in Swedish

I och med upptäckten av antibiotika i första halvan av 1900-talet så kan flera tidigare dödliga infektionssjukdomar botas. Så är längre dock inte alltid fallet, en viss nivå av antibiotikaresistans har upptäckts hos flera stammar av kliniskt viktiga bakterier. Problemet med antibiotikaresistans har till viss del lösts med modifiering av existerande antibiotika, vilket därmed förlängt deras användningstid. Det står dock klart att behovet av nya antibiotika och nya mål för dessa är stort i kampen mot resistenta bakterier



Den här avhandlingen belyser proteiner som innehåller heme, deras funktion och relevans för gram-positiva bakterier samt möjligheten att använda dom som mål för... (More)
Popular Abstract in Swedish

I och med upptäckten av antibiotika i första halvan av 1900-talet så kan flera tidigare dödliga infektionssjukdomar botas. Så är längre dock inte alltid fallet, en viss nivå av antibiotikaresistans har upptäckts hos flera stammar av kliniskt viktiga bakterier. Problemet med antibiotikaresistans har till viss del lösts med modifiering av existerande antibiotika, vilket därmed förlängt deras användningstid. Det står dock klart att behovet av nya antibiotika och nya mål för dessa är stort i kampen mot resistenta bakterier



Den här avhandlingen belyser proteiner som innehåller heme, deras funktion och relevans för gram-positiva bakterier samt möjligheten att använda dom som mål för nya antibiotika. Hemeproteiner finns hos i princip varje levande organism och har många gånger viktiga funktioner. Varje hemeprotein har en eller flera av den järninnehållande kofaktorn heme men kan i övrigt vara väldigt diversa. I den här avhandlingen har tre grupper av hemeproteiner från bakterier studerats närmare. Den första är trunkerade hemoglobin, en grupp som tillhör globin-superfamiljen och som har en fascinerande förmåga att binda ligander och en möjlig förmåga att försvara cellen mot kvävemonoxid. Det andra hemeproteinet är ett protein som tidigare inte har raporterats som ett hemebindande protein, proteinet är involverat i den kovalenta inbindningen av heme till cytokrom c hos gram-positiva bakterier. Det tredje proteinet är cytokrom bd, ett alternativt terminalt oxidas som är unikt för bakterier. Cytokrom bd används vid låga koncentrationer av syre. Inga av dessa tre hemeproteiner finns hos människor. Arbetet med dessa hemeproteiner diskuteras med möjligheten att använda dom som mål för nya antibiotika i åtanke. (Less)
Abstract
With the discovery of antibiotics, several diseases that were previously lethal is today readily cured, or so we thought. Some degree of resistance to one or several antibiotics can be found among many strains of clinical important bacteria. The problem has been somewhat kept at bay for the last few decades by altering already existing antibiotics, and thereby prolonging their usage. It is clear that there is an urgent need to develop new strategies in designing novel antibacterials and to find new drug targets in attempts to overcome bacterial resistance.



This report will review haem containing proteins, their function and relevance to gram-positive bacteria and their possible role as novel antibiotic drug targets.... (More)
With the discovery of antibiotics, several diseases that were previously lethal is today readily cured, or so we thought. Some degree of resistance to one or several antibiotics can be found among many strains of clinical important bacteria. The problem has been somewhat kept at bay for the last few decades by altering already existing antibiotics, and thereby prolonging their usage. It is clear that there is an urgent need to develop new strategies in designing novel antibacterials and to find new drug targets in attempts to overcome bacterial resistance.



This report will review haem containing proteins, their function and relevance to gram-positive bacteria and their possible role as novel antibiotic drug targets. Haemproteins can be found in virtually all living organisms and often have important functions. All haemproteins possess one or more of the iron containing cofactor haem but can otherwise be very diverse. Three groups of haemproteins have been looked at in more detail. The first is truncated haemoglobin, a group belonging to the globin superfamily with intriguing ligand-binding capabilities and a possible function in NO resistance. The second is a novel haem binding protein that is involved in the maturation pathway of covalent haem attachment to cytochrome c in gram-positive bacteria. The last one is cytochrome bd, an alternative terminal oxidase unique to bacteria that is used during low oxygen tension. None of these three haemproteins can be found in a human host. The work done on these three proteins is discussed to assess the plausibility for these haemproteins to act as drug targets. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Ingmer, Hanne, Microbial Food Safety and Hygiene, Department of Veterinary Pathobiology, University of Copenhagen,
organization
publishing date
type
Thesis
publication status
published
subject
keywords
bacteriology, virology, mycology, Mikrobiologi, Microbiology, heme, Truncated hemoglobins, cytochrome c maturation, cytochrome bd, ResB, bakteriologi, virologi, mykologi
pages
147 pages
publisher
Department of Cell and Organism Biology, Lund University
defense location
Hörsalen, Biologihuset Sölvegatan 35 223 62 Lund
defense date
2007-05-03 10:00
ISBN
978-91-85067-31-2
language
English
LU publication?
yes
id
7d01430d-311a-4027-b0c9-4bec21a73984 (old id 548396)
date added to LUP
2007-09-05 10:08:11
date last changed
2016-09-19 08:45:11
@misc{7d01430d-311a-4027-b0c9-4bec21a73984,
  abstract     = {With the discovery of antibiotics, several diseases that were previously lethal is today readily cured, or so we thought. Some degree of resistance to one or several antibiotics can be found among many strains of clinical important bacteria. The problem has been somewhat kept at bay for the last few decades by altering already existing antibiotics, and thereby prolonging their usage. It is clear that there is an urgent need to develop new strategies in designing novel antibacterials and to find new drug targets in attempts to overcome bacterial resistance.<br/><br>
<br/><br>
This report will review haem containing proteins, their function and relevance to gram-positive bacteria and their possible role as novel antibiotic drug targets. Haemproteins can be found in virtually all living organisms and often have important functions. All haemproteins possess one or more of the iron containing cofactor haem but can otherwise be very diverse. Three groups of haemproteins have been looked at in more detail. The first is truncated haemoglobin, a group belonging to the globin superfamily with intriguing ligand-binding capabilities and a possible function in NO resistance. The second is a novel haem binding protein that is involved in the maturation pathway of covalent haem attachment to cytochrome c in gram-positive bacteria. The last one is cytochrome bd, an alternative terminal oxidase unique to bacteria that is used during low oxygen tension. None of these three haemproteins can be found in a human host. The work done on these three proteins is discussed to assess the plausibility for these haemproteins to act as drug targets.},
  author       = {Kjelgaard, Peter},
  isbn         = {978-91-85067-31-2},
  keyword      = {bacteriology,virology,mycology,Mikrobiologi,Microbiology,heme,Truncated hemoglobins,cytochrome c maturation,cytochrome bd,ResB,bakteriologi,virologi,mykologi},
  language     = {eng},
  pages        = {147},
  publisher    = {ARRAY(0x8643818)},
  title        = {Studies on Haemproteins of Gram-positive Bacteria - Implications as Antibacterial Drug Targets},
  year         = {2007},
}