Microbes Lecture 17

Gram-negative autoinducers

Acyl-homoserine lactones (AHL)

Gram-positive proteins

autoinducing peptides

quorum quenching

the biological process where microbes disrupt or “jam” the cell-to-cell communication signals that microbes use to coordinate behaviors like virulence and biofilm formation

Quorum quenching methods

enzymatic degradation, receptor antagonism, autoinducer synthesis inhibition

enxymatic degradation

microbes use enzymes capable of cleaving autoinducers to prevent signals from the enemy from reaching threshold levels and being recognized by receptors

Enzymes for Enzymatic Degradation

AHL Lactonases, AHL Acylases/Amidases, AHL Ocidoreductases, AIP Proteases

Receptor Antagonism

administering natural microbes that block the bacterial receptor sites with a decoy signal to prevent signal perception (receptor binds to a similar-looking decoy signal and then can no longer hear or do anything)

Receptor Antagonism Example

Bacillus species in the gut produce fengycin, a lipopeptide that binds to and blocks the receptor for S. aureus’ quorum sensing system, preventing S. aureus from colonizing and causing food-poisoning symptoms

Autoinducer Synthesis Inhibition

antagonistic bacteria produce compounds that inhibit the internal enxymes competitors need to synthesize autoinducers in the first place (produce similar molecule that binds to the synthase and inactivates it, blocking signal production to prevent virulence and biofilm formation)

Precursor molecules necessary for synthesis

SAM and Acyl-CoA

Challenges for Quorum Quenching

In Vivo Stability, Resistance Potential, Delivery Systems

In Vivo Stability

how long can therapeutic enzymes actually survive

Resistance Potential

bacteria can develop resistance against QQ agents through efflux pump upregulation or structural mutations

Delivery Systems

developing targeted delivery vehicles to protect QQ agents through the gastric environment for delivery to deep organs such as the heart or liver