Unraveling the bacterial exoskeleton: functional and structural characterisation of the B. anthracis S-layer

S-layers are paracriystalline protein monolayers that cover the cell
surface of many Bacteria and nearly all Archaea. They are amongst
the most abundant biopolymers on Earth, yet they have largely
remained a biological enigma.

Recently, developing and applying Slayer disrupting nanobodies (NbsDS) as new bio-tools to control Slayer polymerization, I provided the first evidence for an exoskeletal
role of the S-layer which, when acutely disrupted, results in severe
defects in cell integrity. In vivo studies have proven the therapeutic
potential of Nbs against S-layer carrying pathogens such as Bacillus
anthracis. B. anthracis, the etiological agent of anthrax, represents
an interesting model to study S-layers: two mutually exclusive Slayers, sequentially appear at the cell surface in a growth phasedependent manner. Building on these novel findings and technology,
with this interdisciplinary project, I will investigate: 1) the molecular
mechanisms and dynamics that are driving S-layer formation and
remodeling in response to developmental and environmental triggers
in function of bacterial cell cycle, host infection and stress responses.
2) the novel S-layer exoskeletal role.

The new insights gained in this
study will provide fundamental insights into the biological function of
S- layers, as well as, a platform for the design of novel therapies
against S-layer carrying pathogens able to circumvent drug efflux as
a major multidrug resistance mechanism.