An Iron-Regulated Autolysin Remodels the Cell Wall To Facilitate Heme Acquisition in Staphylococcus lugdunensis

Abstract

Bacteria alter their cell surface in response to changing environments, including those encountered upon invasion of a host during infection. One alteration that occurs in several Gram-positive pathogens is the presentation of cell wall-anchored components of the iron-regulated surface determinant (Isd) system, which extracts heme from host hemoglobin to fulfill the bacterial requirement for iron. Staphylococcus lugdunensis, an opportunistic pathogen that causes infective endocarditis, encodes an Isd system. Unique among the known Isd systems, S. lugdunensis contains a gene encoding a putative autolysin located adjacent to the Isd operon. To elucidate the function of this putative autolysin, here named IsdP, we investigated its contribution to Isd protein localization and hemoglobin-dependent iron acquisition. S. lugdunensis IsdP was found to be iron regulated and cotranscribed with the Isd operon. IsdP is a specialized peptidoglycan hydrolase that cleaves the stem peptide and pentaglycine crossbridge of the cell wall and alters processing and anchoring of a major Isd system component, IsdC. Perturbation of IsdC localization due to isdP inactivation results in a hemoglobin utilization growth defect. These studies establish IsdP as an autolysin that functions in heme acquisition and describe a role for IsdP in cell wall reorganization to accommodate nutrient uptake systems during infection.

CtaM Is Required for Menaquinol Oxidase aa 3 Function in Staphylococcus aureus

“…Bacterial RNA was harvested as previously described ( 42 ). Briefly, overnight cultures of S. aureus were subcultured (1:100) into TSB and cultures were harvested at late exponential phase (6 h) or stationary phase (12 h).…”

Heme Synthesis and Acquisition in Bacterial Pathogens

“…In addition to S. aureus and B. anthracis , many other pathogens have evolved NEAT-containing heme acquisition systems, including Staphylococcus lugdunensis, L. monocytogenes, and Streptococcus pyogenes [136–143]. The conservation of NEAT-mediated heme uptake highlights the contribution of host heme to bacterial infection.…”

Is Staphylococcus lugdunensis Significant in Clinical Samples?

“…Iron plays a crucial role in bacterial metabolism and growth. Staphylococcus lugdunensis is the only CoNS that carries a complete operon dedicated to iron capture and metabolism that encodes the iron-regulated proteins, IsdB, IsdC, IsdJ, and IsdK (36). It is the only CoNS that has a captation system similar to that of S. aureus.…”