TY - JOUR
T1 - Contemporary clinical isolates of Staphylococcus aureus from pediatric osteomyelitis patients display unique characteristics in a mouse model of hematogenous osteomyelitis
AU - Roper, Philip M.
AU - Eichelberger, Kara R.
AU - Cox, Linda
AU - O’Connor, Luke
AU - Shao, Christine
AU - Ford, Caleb A.
AU - Fritz, Stephanie A.
AU - Cassat, James E.
AU - Veis, Deborah J.
N1 - Funding Information:
This work was supported by National Institutes of Health grants R21 AR073507 and R01 AR070030 (D.J.V.) and by Shriners Hospitals for Children grant 85117 (D.J.V.). P.M.R. was supported by Skeletal Disorders Training Program grant T32 AR060719. J.E.C. was supported by grant R01AI132560 (NIAID), grant R01AI145992 (NIAID), and a career award for medical scientists from the Burroughs Wellcome Fund. K.R.E. was supported by Childhood Infection Research Program grant T32 AI095303. C.A.F. was supported through grant T32GM007347 (NIGMS) and is supported by grant F30AI138424 (NIAID). The bioluminescence imaging was performed at the Washington University School of Medicine Molecular Imaging Center, supported by NIH grant P50 CA094056 (Molecular Imaging Center) and NCI grant P30 CA091842 (Siteman Cancer Center Small Animal Cancer Imaging Shared Resource). The Washington University Musculoskeletal Research Center, supported by grant P30 R074992, provided resources for microCT through its Structure and Strength Core and histology via its Histology and Morphometry Core. Sequencing was performed by the Washington University Genome Technology Access Center.
Funding Information:
This work was supported by National Institutes of Health grants R21 AR073507 and R01 AR070030 (D.J.V.) and by Shriners Hospitals for Children grant 85117 (D.J.V.). P.M.R. was supported by Skeletal Disorders Training Program grant T32 AR060719. J.E.C. was supported by grant R01AI132560 (NIAID), grant R01AI145992 (NIAID), and a career award for medical scientists from the Burroughs Wellcome Fund. K.R.E. was supported by Childhood Infection Research Program grant T32 AI095303. C.A.F. was supported through grant T32GM007347 (NIGMS) and is supported by grant F30AI138424 (NIAID). The bioluminescence imaging was performed at the Washington University School of Medicine Molecular Imaging Center, supported by NIH grant P50 CA094056 (Molecular Imaging Center) and NCI grant P30 CA091842 (Siteman Cancer Center Small Animal Cancer Imaging Shared Resource). The Washington University Musculoskeletal Research Center, supported by grant P30 R074992, provided resources for microCT through its Structure and Strength Core and histology via its Histology and Morphometry Core. Sequencing was performed by the Washington University Genome Technology Access Center. We thank Crystal Idleburg and Samantha Coleman for expert histology, Roger Plaut for providing the lux operon plasmid pRP1195, Victor Torres for providing the mCherry S. aureus strain, Valeria Reyes Ruiz and Brittney Gimza for technical support with strain construction, and Julie Prior and Katie Duncan for their bioluminescence imaging assistance.
Publisher Copyright:
© 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/10
Y1 - 2021/10
N2 - Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized the resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over 5 weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in the trabecular bone volume fraction but little effect on bone cortices. Histological assessment revealed differences in the precise focus of musculoskeletal infection, with various mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole-genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.
AB - Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized the resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over 5 weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in the trabecular bone volume fraction but little effect on bone cortices. Histological assessment revealed differences in the precise focus of musculoskeletal infection, with various mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole-genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.
KW - Clinical isolates
KW - Hematogenous osteomyelitis
KW - Pediatric infectious disease
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=85115956213&partnerID=8YFLogxK
U2 - 10.1128/IAI.00180-21
DO - 10.1128/IAI.00180-21
M3 - Article
C2 - 34097469
AN - SCOPUS:85115956213
SN - 0019-9567
VL - 89
JO - Infection and Immunity
JF - Infection and Immunity
IS - 10
M1 - e00180-21
ER -