1 research outputs found
Understanding the Structure–Function Relationship of Lysozyme Resistance in Staphylococcus aureus by Peptidoglycan O‑Acetylation Using Molecular Docking, Dynamics, and Lysis Assay
Lysozyme is an important component
of the host innate defense system.
It cleaves the β-1,4 glycosidic bonds between <i>N</i>-acetylmuramic acid and <i>N</i>-acetylglucosamine of bacterial
peptidoglycan and induce bacterial lysis. Staphylococcus
aureus (S. aureus),
an opportunistic commensal pathogen, is highly resistant to lysozyme,
because of the O-acetylation of peptidoglycan by <i>O</i>-acetyl transferase (<i>oatA</i>). To understand the structure–function
relationship of lysozyme resistance in S. aureus by peptidoglycan O-acetylation, we adapted an integrated approach
to (i) understand the effect of lysozyme on the growth of S. aureus parental and the <i>oatA</i> mutant
strain, (ii) study the lysozyme induced lysis of exponentially grown
and stationary phase of both the S. aureus parental and <i>oatA</i> mutant strain, (iii) investigate
the dynamic interaction mechanism between normal (de-O-acetylated)
and O-acetylated peptidoglycan substrate in complex with lysozyme
using molecular docking and molecular dynamics simulations, and (iv)
quantify lysozyme resistance of S. aureus parental and the <i>oatA</i> mutant in different human
biological fluids. The results indicated for the first time that the
active site cleft of lysozyme binding with O-acetylated peptidoglycan
in S. aureus was sterically hindered
and the structural stability was higher for the lysozyme in complex
with normal peptidoglycan. This could have conferred reduced survival
of the S. aureus <i>oatA</i> mutant in different human biological fluids. Consistent with this
computational analysis, the experimental data confirmed decrease in
the growth, lysozyme induced lysis, and lysozyme resistance, due to
peptidoglycan O<i>-</i>acetylation in S.
aureus