Difference between revisions of "Glycylcycline Antibiotics"

From MicrobeWiki, the student-edited microbiology resource
Line 1: Line 1:
 
==Introduction==
 
==Introduction==
<br>Kristina Buschur<br><br>The ability of bacteria to quickly develop resistance to commonly used antibiotics is a huge hurdle in the path of disease treatment.  Because of this, there is an ever-present need to develop new antibiotics that are use novel mechanisms to overcome multidrug-resistance and prevent microbial growth.  The glycylcycline class of antibiotics is such one recently-developed tool to combat this problem. Derived from tetracycline, glycylcyclines have added substituents that interfere with the mechanisms bacteria employ to resist tetracycline, such as efflux pumps and ribosomal protection.  Since tetracycline has been in wide use since the mid-1900s, many bacteria have since developed these mechanisms to prevent the harmful effects of tetracycline. <br><br>
+
<br>Kristina Buschur<br><br>The ability of bacteria to quickly develop resistance to commonly used antibiotics is a huge hurdle in the path of disease treatment.  Because of this, there is an ever-present need to develop new antibiotics that are use novel mechanisms to overcome multidrug-resistance and prevent microbial growth.  The glycylcycline class of antibiotics is such one recently-developed tool to combat this problem. Derived from tetracycline, glycylcyclines have added substituents that interfere with the mechanisms bacteria employ to resist tetracycline, such as tetracycline-specific efflux pumps and ribosomal protection proteins.  Since tetracycline has been in wide use since the mid-1900s for treatment of many human and animal infections and as growth promoters in agriculture, many bacteria have since developed these mechanisms to prevent the harmful effects of tetracycline. <br><br>
Currently tigecycline is the only antibiotic of the glycylcycline class in clinical use.  Tigecycline was approved by the Food and Drug Administration in 2005, and is particularly useful in the treatment of infections of gram-positive bacteria, which are typically especially hard to treat.  Penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and vancomycin-resistant Enterococcus species are several examples of species that have developed an antibiotic resistance but are still affected by tigecycline.  The antibiotic is structurally very similar to minocycline and similarly binds to the bacterial 30S ribosome unit.  The manner in which the molecule binds prevents amino-acyl tRNAs from binding to the A site of the ribosome and subsequently prevents peptide formation and bacterial growth.  Furthermore, the main difference between tigecycline and minocycline is the addition of an N,N-dimethylglycylamido group which actually causes the molecule to bind to the ribosome up to five times more tightly and decreases the probability that resistance will develop. <br><br>
+
Currently tigecycline (previously GAR-936) is the only antibiotic of the glycylcycline class in clinical use.  Tigecycline was approved by the Food and Drug Administration in 2005, and is particularly useful in the treatment of multi-drug resistant infections, which are especially hard to treat.  Penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and vancomycin-resistant Enterococcus species are several examples of species that have developed an antibiotic resistance but are still affected by tigecycline.  In addition to these, there is a wide variety of organisms, including both gram-positive and gram-negative bacteria, that are sensitive to tigecycline.  It does not, however, seem to have any effect of Proteus, Providencia, or Pseudomons species.  The antibiotic is structurally very similar to minocycline and similarly binds to the bacterial 30S ribosome unit.  The manner in which the molecule binds prevents amino-acyl tRNAs from binding to the A site of the ribosome and subsequently prevents peptide formation and bacterial growth.  Furthermore, the main difference between tigecycline and minocycline is the addition of an N,N-dimethylglycylamido group which actually causes the molecule to bind to the ribosome up to five times more tightly and decreases the probability that resistance will develop. <br><br>
Tigecycline is administered to a patient intravenously with a dose of 50 mg every 12 hours after an initial 100 mg loading dose.  As with nearly all drugs, the antibiotic has several known side-effects, including nausea, vomiting, and diarrhea.
+
The glycylcycline class of antibiotics is characterized by a molecular structure containing a four-ring carbocyclic skeleton with a substitution of an N-alkylglycylamido group at the D-9 position.  Biochemical experiments have shown that the tigecycline binds to the same site on 16S rRNA as tetracycline but in a different orientation and with greater affinity.  This has been confirmed by experiments in which a decreased binding affinity was observed in strains of E. coli  with known mutations in the A site in the rRNA (G966U or G1058C).  <br><br>
 +
Tigecycline is administered to a patient intravenously with a dose of 50 mg every 12 hours after an initial 100 mg loading dose.  As with nearly all drugs, the antibiotic has several known side-effects, including nausea, vomiting, and diarrhea, but these are relatively minor.  Barring severe complications, the treatment period usually ranges from five to fourteen days.  
  
 
<br>
 
<br>

Revision as of 21:08, 15 April 2009

Introduction


Kristina Buschur

The ability of bacteria to quickly develop resistance to commonly used antibiotics is a huge hurdle in the path of disease treatment. Because of this, there is an ever-present need to develop new antibiotics that are use novel mechanisms to overcome multidrug-resistance and prevent microbial growth. The glycylcycline class of antibiotics is such one recently-developed tool to combat this problem. Derived from tetracycline, glycylcyclines have added substituents that interfere with the mechanisms bacteria employ to resist tetracycline, such as tetracycline-specific efflux pumps and ribosomal protection proteins. Since tetracycline has been in wide use since the mid-1900s for treatment of many human and animal infections and as growth promoters in agriculture, many bacteria have since developed these mechanisms to prevent the harmful effects of tetracycline.

Currently tigecycline (previously GAR-936) is the only antibiotic of the glycylcycline class in clinical use. Tigecycline was approved by the Food and Drug Administration in 2005, and is particularly useful in the treatment of multi-drug resistant infections, which are especially hard to treat. Penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and vancomycin-resistant Enterococcus species are several examples of species that have developed an antibiotic resistance but are still affected by tigecycline. In addition to these, there is a wide variety of organisms, including both gram-positive and gram-negative bacteria, that are sensitive to tigecycline. It does not, however, seem to have any effect of Proteus, Providencia, or Pseudomons species. The antibiotic is structurally very similar to minocycline and similarly binds to the bacterial 30S ribosome unit. The manner in which the molecule binds prevents amino-acyl tRNAs from binding to the A site of the ribosome and subsequently prevents peptide formation and bacterial growth. Furthermore, the main difference between tigecycline and minocycline is the addition of an N,N-dimethylglycylamido group which actually causes the molecule to bind to the ribosome up to five times more tightly and decreases the probability that resistance will develop.

The glycylcycline class of antibiotics is characterized by a molecular structure containing a four-ring carbocyclic skeleton with a substitution of an N-alkylglycylamido group at the D-9 position. Biochemical experiments have shown that the tigecycline binds to the same site on 16S rRNA as tetracycline but in a different orientation and with greater affinity. This has been confirmed by experiments in which a decreased binding affinity was observed in strains of E. coli with known mutations in the A site in the rRNA (G966U or G1058C).

Tigecycline is administered to a patient intravenously with a dose of 50 mg every 12 hours after an initial 100 mg loading dose. As with nearly all drugs, the antibiotic has several known side-effects, including nausea, vomiting, and diarrhea, but these are relatively minor. Barring severe complications, the treatment period usually ranges from five to fourteen days.


Section 1


Include some current research in each topic, with at least one figure showing data.

Section 2


Include some current research in each topic, with at least one figure showing data.

Section 3


Include some current research in each topic, with at least one figure showing data.

Conclusion


Overall paper length should be 3,000 words, with at least 3 figures.

References

[Sample reference] Takai, K., Sugai, A., Itoh, T., and Horikoshi, K. "Palaeococcus ferrophilus gen. nov., sp. nov., a barophilic, hyperthermophilic archaeon from a deep-sea hydrothermal vent chimney". International Journal of Systematic and Evolutionary Microbiology. 2000. Volume 50. p. 489-500.

Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.