ArticlePLoS pathogens2020
Identification of Penicillin Binding Protein 4 (PBP4) as a critical factor for Staphylococcus aureus bone invasion during osteomyelitis in mice.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
- Osteomyelitis: Epidemiology, Classification, Pathophysiology, Clinical Features, Diagnosis, and Management.MedComm · 2026Review
- A periplasmic layer formed by an outer membrane lipoprotein governs the cell-envelope integrity and stiffness of Leptospira interrogans.Communications biology · 2026Article
- Osteomyelitis.Nature reviews. Disease primers · 2026Review
- Exploration of a benzothiophene scaffold for use as adjuvants with β-lactam antibiotics against methicillin-resistantRSC medicinal chemistry · 2026Article
- "Antimicrobial Brachytherapy" Protocol for Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: A Preliminary Case Series with 2-Year Results.Journal of clinical medicine · 2026Article
- Clinical Outcome After Surgery for Fracture-Related Infection Is Dependent on Both Microbiology and the Host Inflammatory Response.Pathogens (Basel, Switzerland) · 2026Article
- Article
- Penicillin-Binding Protein-4 (PBP4) ofMicroorganisms · 2026Review
- Microbiome-Targeted Probiotic Strategies for the Prevention and Treatment of Osteomyelitis: A Novel Biological Approach.Probiotics and antimicrobial proteins · 2026Review
- Peptidoglycan architecture dictates protein interactions, tissue tropism, and arthritis in the Lyme disease spirochete Borrelia burgdorferi.PLoS pathogens · 2026Article
- Panoramic description of ROS-based nanotechnology for osteomyelitis therapy: Challenges, opportunities, and prospects.Theranostics · 2026Review
- Microfluidics to Meet Antibiotic Resistance: A Growing Research Frontier.Antibiotics (Basel, Switzerland) · 2025Review
- Biomaterial-mediated macrophage polarization remodeling and sequential regulation: a potential strategy in bone infections treatment.Bone research · 2025Review
- Article
- Phenyl urea based adjuvants for β-lactam antibiotics against methicillin resistant Staphylococcus aureus.Bioorganic & medicinal chemistry letters · 2025Article
- Bisphosphonate-Conjugated Sitafloxacin for Treatment ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Addressing the challenges of infectious bone defects: a review of recent advances in bifunctional biomaterials.Journal of nanobiotechnology · 2025Review
- Antibiotic-Loaded Calcium Sulphate Beads for Treatment of Acute Periprosthetic Joint Infection in Total Knee Arthroplasty: Results Based on Risk Stratification.Journal of clinical medicine · 2025Article
- Immune escape ofFrontiers in cellular and infection microbiology · 2025Review
- Immune Checkpoint Molecules as Biomarkers ofbioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Staphylococcus aureus infection of bone is challenging to treat because it colonizes the osteocyte lacuno-canalicular network (OLCN) of cortical bone. To elucidate factors involved in OLCN invasion and identify novel drug targets, we completed a hypothesis-driven screen of 24 S. aureus transposon insertion mutant strains for their ability to propagate through 0.5 μm-sized pores in the Microfluidic Silicon Membrane Canalicular Arrays (μSiM-CA), developed to model S. aureus invasion of the OLCN. This screen identified the uncanonical S. aureus transpeptidase, penicillin binding protein 4 (PBP4), as a necessary gene for S. aureus deformation and propagation through nanopores. In vivo studies revealed that Δpbp4 infected tibiae treated with vancomycin showed a significant 12-fold reduction in bacterial load compared to WT infected tibiae treated with vancomycin (p<0.05). Additionally, Δpbp4 infected tibiae displayed a remarkable decrease in pathogenic bone-loss at the implant site with and without vancomycin therapy. Most importantly, Δpbp4 S. aureus failed to invade and colonize the OLCN despite high bacterial loads on the implant and in adjacent tissues. Together, these results demonstrate that PBP4 is required for S. aureus colonization of the OLCN and suggest that inhibitors may be synergistic with standard of care antibiotics ineffective against bacteria within the OLCN.
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Registered trials
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