Quorum Sensing in Pathogenic Burkholderias

Aspergillus fumigatus and Invasive Aspergillosis

Bill NiermanBill NiermanJ. Craig Venter InstituteJ. Craig Venter Institute

Rockville, MDRockville, MD

wnierman@jcvi.org

Quorum Sensing Control of Virulence in Pathogenic

Burkholderias

• First describe in Vibrio fischeri in 1979

• Bacteria cell-cell communication mechanism

• Involves autoinducers that are hormone-like in action

• Synchronizes population wide behaviors via transcriptionally controlled regulons

Interaction of Interaction of AspergillusAspergillus with the host with the host

Immune dysfunction

Frequency

of a

sperg

illosis

Immune hyperactivity

Frequency

of

asp

erg

illosi

s

Acute IA

Subacute IA

Tracheobronchitis AspergillomaChronic cavitaryChronic fibrosing

Allergic BPAAllergic sinusitis

. www.aspergillus.man.ac.ukwww.aspergillus.man.ac.uk

Invasive AspergillosisLifetime Risk

• Chronic granulomatosis disease (25-40%)• Transplant recipients (1-25%)

–1% Kidney–10-15% Bone Marrow; Leading cause of infectious death–25% Lung (colonization/infection)

• Neutropenic patients with leukemia (5-25%)–Leading cause of infectious death

• AIDS (4%)• Multiple myeloma (4%)• SCIDS (4%)