Nina Molin Høyland-Kroghsbo:
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Uncovering how bacteria perceive environmental signals and how they interpret these, in order to constantly adapt to changes in their environment, is important for understanding not only microbial ecology but also bacterial pathogenesis. Furthermore, it provides cues as to how we might interfere with these systems, in order to prevent undesirable bacterial behavior.
In a process known as quorum sensing, bacteria emit and detect small diffusible molecules, which upon reaching a certain extracellular concentration, activate cellular quorum sensing receptors and thereby turn on group behavior genes. Quorum sensing controls important bacterial behaviors, including bioluminescence, biofilm formation, and virulence. Inter- and intraspecies quorum sensing signals enable bacteria to estimate the abundance and species complexity of a microbial community. A long standing question in the bacterial cell-cell communication field is why E. coli harbors SdiA, an orphan quorum sensing receptor that is activated in response to AHL quorum sensing molecules produced by other Gram-negative species.
The overall aim of this PhD thesis was to investigate to what degree AHL quorum sensing signals are exploited by E. coli to increase its chances of surviving potential environmental threats. This thesis uncovers the first quorum sensing-regulated bacteriophage defense mechanism, which serves to protect E. coli against infection by the bacteriophage viruses λ and χ. Investigating the regulatory mechanism underlying the quorum sensing regulated defense mechanism, led to the discovery that AHL activates expression of cnu, encoding an Hha-family protein that interacts with the global regulatory protein H-NS, and potentially modifies its functions.
Inspired by the discovery that AHL protects E. coli from bacteriophage attacks, it was hypothesized that AHL may be perceived by E. coli as a general signal of stress in the environment. Indeed, it was discovered that AHL signaling upregulates the alternative sigma factor δS, the master regulator of the general stress response in E. coli. AHL-mediated activation of the general stress response also resulted in an increase in transiently antibiotic tolerant persister cells in E. coli.
In conclusion, this thesis provides a key answer to why E. coli listens in on AHL signals it does not itself produce, namely that detection of interspecies AHL quorum sensing by E. coli serves to anticipate- and adapt to environmental stresses. This discovery may have important clinical implications, as quorum sensing-inhibitory drugs may, in addition to their primary purpose to decrease virulence of pathogens, additionally weaken bacterial defenses thus making them prone to succumb to a patient’s own immune system, bacteriophages, and antibiotics, and would additionally reduce the risk of persister cell formation and thus relapse of infection after an antibiotic treatment.