Recent advances in experimental models of osteomyelitis

Cassat, James E.; Skaar, Eric P.

doi:10.1586/14787210.2013.858600

Cited by 13 publications

(10 citation statements)

References 20 publications

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“…Therefore, early diagnosis and initiation of proper treatment are essential to obtain a better outcome and avoid sequelae. Furthermore, the emergence of bacterial strains particularly virulent and resistant to antibiotics has made the treatment of these conditions more difficult than in the past and has led to the need to have new antibiotic molecules available to deal with these emergencies [ 7 , 9 ]. However, there is no consensus in the literature regarding the best antibiotic therapy to be administered, the mode of administration, and the duration of therapy.…”

Section: Introductionmentioning

confidence: 99%

Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis

Castellazzi

Mantero

Esposito

2016

IJMS

140

119

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Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based on prolonged intravenous anti-infective therapy. However, results from clinical trials have suggested that in uncomplicated cases, a short course of a few days of parenteral antibiotics followed by oral therapy is safe and effective. The aim of this review is to provide clinicians an update on recent controversies and advances regarding the management of acute osteomyelitis and septic arthritis in children. In recent years, the emergence of bacterial species resistant to commonly used antibiotics that are particularly aggressive highlights the necessity for further research to optimize treatment approaches and to develop new molecules able to fight the war against acute osteoarticular infection in pediatric patients.

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Section: Introductionmentioning

confidence: 99%

Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis

Castellazzi

Mantero

Esposito

2016

IJMS

140

119

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“…Indeed, it has been suggested that, as with cancer, "remission" is a more appropriate term than "cure" in the context of osteomyelitis (2). Several factors contribute to this therapeutic recalcitrance, including the inability to diagnose the infection before it has progressed to a chronic stage in which the local vasculature is compromised, the formation of a bacterial biofilm that limits the efficacy of both conventional antibiotics and host defenses, the emergence of phenotypic variants within the biofilm (persister cells and small-colony variants) that exhibit metabolic traits that limit their antibiotic susceptibility, and the ability of the pathogens involved, including S. aureus, to invade and replicate within host cells, including osteoblasts (3)(4)(5)(6)(7)(8)(9). Collectively, these factors dictate that the clinical problem of osteomyelitis extends far beyond acquired resistance and the increasingly limited availability of effective antibiotics.…”

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confidence: 99%

Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus

et al. 2016

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eWe used a murine model of acute, posttraumatic osteomyelitis to evaluate the virulence of two divergent Staphylococcus aureus clinical isolates (the USA300 strain LAC and the USA200 strain UAMS-1) and their isogenic sarA mutants. The results confirmed that both strains caused comparable degrees of osteolysis and reactive new bone formation in the acute phase of osteomyelitis. Conditioned medium (CM) from stationary-phase cultures of both strains was cytotoxic to cells of established cell lines (MC3TC-E1 and RAW 264.7 cells), primary murine calvarial osteoblasts, and bone marrow-derived osteoclasts. Both the cytotoxicity of CM and the reactive changes in bone were significantly reduced in the isogenic sarA mutants. These results confirm that sarA is required for the production and/or accumulation of extracellular virulence factors that limit osteoblast and osteoclast viability and that thereby promote bone destruction and reactive bone formation during the acute phase of S. aureus osteomyelitis. Proteomic analysis confirmed the reduced accumulation of multiple extracellular proteins in the LAC and UAMS-1 sarA mutants. Included among these were the alpha class of phenol-soluble modulins (PSMs), which were previously implicated as important determinants of osteoblast cytotoxicity and bone destruction and repair processes in osteomyelitis. Mutation of the corresponding operon reduced the cytotoxicity of CM from both UAMS-1 and LAC cultures for osteoblasts and osteoclasts. It also significantly reduced both reactive bone formation and cortical bone destruction by CM from LAC cultures. However, this was not true for CM from cultures of a UAMS-1 psm ␣ mutant, thereby suggesting the involvement of additional virulence factors in such strains that remain to be identified.

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“…Gastrointestinal endoscopes have been developed that emit wavelengths that activate porphyrins in patients to detect cancer, and similar strategies have been interrogated for their ability to treat gastrointestinal infections (38,39). Osteomyelitis and contamination of orthopedic devices are some of the most common invasive bacterial infections, and PDT strategies to combat these infections are being developed (40)(41)(42)(43)(44)(45)(46). Finally, PDT-based strategies are in development for a variety of other diseases, including parasitic, dental, and sinus infections (47,48).…”

Section: Discussionmentioning

confidence: 99%

Antibacterial photosensitization through activation of coproporphyrinogen oxidase

Surdel

Horvath

Lojek

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Gram-positive bacteria cause the majority of skin and soft tissue infections (SSTIs), resulting in the most common reason for clinic visits in the United States. Recently, it was discovered that Gram-positive pathogens use a unique heme biosynthesis pathway, which implicates this pathway as a target for development of antibacterial therapies. We report here the identification of a small-molecule activator of coproporphyrinogen oxidase (CgoX) from Gram-positive bacteria, an enzyme essential for heme biosynthesis. Activation of CgoX induces accumulation of coproporphyrin III and leads to photosensitization of Gram-positive pathogens. In combination with light, CgoX activation reduces bacterial burden in murine models of SSTI. Thus, small-molecule activation of CgoX represents an effective strategy for the development of light-based antimicrobial therapies.

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Recent advances in experimental models of osteomyelitis

Cited by 13 publications

References 20 publications

Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis

Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis

Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus

Antibacterial photosensitization through activation of coproporphyrinogen oxidase

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