Abstract
In Staphylococcus aureus, the accessory gene regulator (agr)
quorum-sensing system is thought to play an important role
in biofilm formation. The histidine kinase AgrC is one of the
agr system components and activated by the self-generated
auto-inducing peptide (AIP), which is released continuously
into the extracellular environment during bacterial growth.
The extracellular loops (Extra-loops) of AgrC are crucial for
AIP binding. Here, we reported that the cytoplasmic loops
(Cyto-loops) of AgrC are also involved in Agr activity. We
identified S. aureus ST398 clinical isolates containing a naturally
occurring single amino acid substitution (lysine to isoleucine)
at position 73 of an AgrC Cyto-loop that exhibited
significantly stronger biofilm formation and decreased Agr
activity compared to the wild-type strain. A constructed strain
containing the K73I point mutation in AgrC Cyto-loop continued
to show a growth dependent induction of the agr system,
although the growth dependent induction was delayed
by about 6 h compared to the wild-type. In addition, a series
of strains containing deletion mutants of the AgrC Cyto- and
Extra-loops were constructed and revealed that the removal
of the two Cyto-loops and Extra-loops 2 and 3 totally abolished
the Agr activity and the growth-dependence on the agr
system induction. Remarkably, the Extra-loop 1 deletion did
not affect the Agr activity. In conclusion, the AgrC Cyto-loops
play a crucial role in the S. aureus quorum-sensing activity.
Citations
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