Structural and Functional Analysis of Bacillus subtilis YisP Reveals a Role of Its Product in Biofilm Production

Abstract

Summary YisP is involved in biofilm formation in Bacillus subtilis and has been predicted to produce C30 isoprenoids. We determined the structure of YisP and observe that it adopts the same fold as squalene and dehydrosqualene synthases. However, the first aspartate-rich motif found in essentially all isoprenoid synthases is aspartate-poor in YisP, and cannot catalyze head-to-head condensation reactions. We find that YisP acts as a phosphatase, catalyzing formation of farnesol from farnesyl diphosphate, and is the first phosphatase to adopt the fold seen in the head-to-head prenyl synthases. Farnesol restores biofilm formation in a Δyisp mutant, and modifies lipid membrane structure similarly to the virulence factor, staphyloxanthin. The work clarifies the role of YisP in biofilm formation and suggests an intriguing possibility that many of the YisP-like homologs found in other bacteria may also have interesting products and functions.

Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance

“…However, prokaryotic membranes compartmentalize diverse cell processes in raft-like regions termed functional membrane microdomains (FMMs), similar to their eukaryotic counterparts ( LaRocca et al., 2013 , López and Kolter, 2010 ). FMM formation in bacteria involves the biosynthesis and aggregation of still-unknown isoprenoid membrane lipids ( Feng et al., 2014 , López and Kolter, 2010 ) and their colocalization with flotillin homolog proteins ( Donovan and Bramkamp, 2009 , López and Kolter, 2010 ). Bacterial flotillins probably recruit protein cargo to FMMs to facilitate protein interaction and oligomerization ( Bach and Bramkamp, 2013 , Koch et al., 2017 , Schneider et al., 2015 ), similar to eukaryotic flotillins.…”

The Bacterial Cytoskeleton Spatially Confines Functional Membrane Microdomains

“…In addition, the lipids of prokaryotic membranes laterally segregate into functional membrane microdomains (FMMs) that compartmentalize proteins involved in different processes such as virulence, protein secretion, biofilm formation and antibiotic resistance 27–47 . The organization of FMMs in bacteria involves the biosynthesis and aggregation of isoprenoid-related membrane saccharolipids 47,48 and their colocalization with flotillin-homolog proteins 47,49 . Bacterial flotillins, like their eukaryotic counterparts, are microdomain-associated scaffold proteins responsible for providing stability to FMMs and for recruiting protein cargo to the latter 27,32,50 .…”

Hybrid genome assembly and annotation of Paenibacillus pasadenensis strain R16 reveals insights on endophytic life style and antifungal activity

“…While we can say very little about how strain R16 performs quorum sensing, it is possible that the high production of farnesol [ 10 ] is related to this function. It was proven in Bacillus subtilis , using a farnesol-production deficient mutant and seeing recovery of wild-type functions by the addition of exogenous farnesol, that farnesol may be needed for the formation of biofilm [ 36 ], a function highly related to quorum sensing. Though this role of farnesol seems to be merely structural, by triggering a relaxation in the rigid structure of the bacterial cell wall bilypid layer, it cannot be excluded that this terpene can have a signaling effect in bacteria, as it does in other organisms such as fungi and plants [ 37 ].…”