Mycobacterium abscessus (Mab) is a rapidly growing environmental species of mycobacteria. It causes skin and soft tissue infections post trauma and surgery as well as bronchopulmonary infection and acute respiratory failure in patients with chronic lung damage. Cystic fibrosis (CF) patients are particularly vulnerable to Mab infections. Cure rates are deplorably low (~50%), involving 6–12-month long regimens of multiple, often noxious, antibiotics and/or, surgical resection.
Mycobacterium abscessus infections are incredibly difficult to treat due to three primary reasons:
- Mab is highly resistant to most FDA approved antibiotics such as rifampicin, isoniazid, ethambutol, tetracyclines and streptomycin, making them unavailable for therapy.
- Mab displays initial susceptibility to some antibiotics (e.g. macrolides) but becomes resistant after extending the testing period. Exposure to antibiotics induces transcription of drug resistance genes resulting in delayed resistance.
- There is a poor correlation between in vitro antibiotic susceptibility and in vivo efficacy, a part of which may be attributed to the ability of Mab to form biofilms.
The primary focus of the lab is to decipher the molecular mechanisms involved in the extreme drug resistance of Mycobacterium abscessus. Specific projects include:
- Systems level understanding of changes that accompany exposure of M. abscessus to antibiotics.
- Identification of effectors that confer unique profiles of drug resistance.
- Screening of small molecule libraries for inhibitors of identified targets.
- Studying the role of biofilm formation on antibiotic resistance of M. abscessus.
We use a combination of bacterial genetics, biochemistry, and high throughput genomic analysis to decipher mechanisms of drug resistance.
- Antibiotic/drug resistance
- Systems biology
- Biofilm formation
- Bacterial pathogenesis
- Infection and immunity
- Genes and genomes