I. Bacterial Infections
The dramatic increase in antibiotic resistant bacteria, often referred to as "super-bugs", has emphasized the need for new antibiotics. This need is especially felt in hospitals where untreatable nosocomial infections, such as VRE and MRSA, have caused ward closures and sometimes deaths. Many health scientists fear that, if we are unable to develop new antibiotics, we will soon be entering the "post-antibiotic area", calling up images of the bubonic plague.
Several strategies can be conceived for developing, the much needed new and effective treatments against pathogenic bacteria, for example:
1. Combating Antibiotic Resistance
By disrupting the bacterial resistance mechanisms, conventional antibiotics should become effective again.
2. Inhibiting Essential Biochemical Pathways unique to Bacteria
Derailing essential processes in bacteria is an effective approach for the development of antibiotics. In fact, most currently available antibiotics do exactly that.
3. Exploiting Genomics Information for the Development of Novel Antibiotics
The wealth of information coming from genomics efforts can be harnessed for the development of novel antibiotics, through the identification of previously unknown but essential proteins.
The Berghuis lab is pursuing all three strategies for the development of novel antibacterial agents.
- Structural Studies of Antibiotic Resistance Enzymes
- Structural studies of biosynthesis enzymes
- Structural Studies of essential unknowns unique to bacteria
II. Fungal Infections
When discussing the treat of microbial infections, frequently only viral infections (e.g. AIDS) or bacterial infections (e.g. VRE and MRSA) are considered. However, fungal infections have also become a major cause of concern. In recent years the number of life-threatening fungal infections (systemic mycoses) has dramatically increased. A good example of such an infection is oral thrush (candidiasis), which is caused by the human pathogen Candida albicans.
The reason for the surge in fungal infections is threefold. First, there has been a significant increase in immuno-compromised patients (e.g. organ transplant recipients and AIDS patients), a group who is particularly susceptible to pathogenic fungal infections. The second reason is that, fungi have developed drug resistance against many commonly used antifungal agents, thus complicating treatment. And finally, species of fungi which previously did not pose a threat to our health have now become the cause of new invasive fungal infections.
In order to combat the dangers of systemic mycoses, it is clear that new antimicrobial agents need to be developed. One possible avenue which can be taken in the development of fungicides is the exploitation of biological differences between fungi and humans, such as the differences in amino-acid metabolism. The Berghuis Lab is pursing this avenue.
- Structural studies of enzymes of the fungal aspartate pathway