Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection
Abstract
:1. Introduction
2. Material and Methods
2.1. Setting and Patients
2.2. Antimicrobial Susceptibility Testing
2.3. Characterization of Hemolytic Activity
2.4. Biofilm Formation
2.5. Fibronectin Adhesion Assay
2.6. Cytotoxicity Assay on MG63 Osteoblasts
2.7. Adhesion, Invasion and Persistence Intracellular Assay
2.8. Whole Genome Sequencing
2.9. Statistical Analysis
3. Results
3.1. Genotypic and Phenotypic Comparisons of Isolates from Resolved and Recurrent PJIs
3.2. Phenotypic and Genotypic Changes during Persistent and Relapsing S. aureus PJIs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Strain Code | Sex, Age (years) | Infection location | Type of Infection 2 | Duration of Antibiotherapy (days) 3 | Outcome 4 | Antimicrobial Resistance | Hemolytic Activity | Biofilm | ST 5 | ||
---|---|---|---|---|---|---|---|---|---|---|---|
α-Hemolysin (hla) | β-Hemolysin (hlb) | δ-Hemolysin (agr) | |||||||||
FailRel104.1 | F, 63 | Knee | EPI | 60 | - | PEN | Positive | Negative | Strong | Weak | 15 |
FailRel104.2 | - | Relapse | † | Negative | Negative | Strong | Weak | 15 | |||
FailRel107.1 | F, 86 | Knee | AHI | 66 | - | PEN, CL, GEN, CIP, LEV | Positive | Positive | Negative | Weak | 398 |
FailRel107.2 | - | Relapse | PEN, CL, GEN CIP, LEV | Positive | Positive | Negative | Weak | 398 | |||
FailRel409.1 | F, 87 | Hip | EPI | 37 | - | PEN, CIP | Positive | Negative | Weak | Weak | 188 |
FailRel409.2 | - | Relapse | PEN, CIP | Positive | Negative | Weak | Moderate | 188 | |||
FailPer401.1 | F, 65 | Knee | EPI | 144 | - | PEN, GEN | Positive | Negative | Strong | Weak | 45 |
FailPer401.2 | - | Persistence | PEN | Positive | Negative | Strong | Weak | 45 | |||
FailPer402.1 | M, 81 | Knee | AHI | 78 | - | PEN | Positive | Negative | Weak | Weak | 5 |
FailPer402.2 | - | Persistence | PEN | Positive | Negative | Weak | Weak | 5 | |||
FailPer118.1 | F, 78 | Hip | EPI | 25 | - | PEN, MET, ER, CIP, LEV | Positive | Negative | Strong | Moderate | 125 |
FailPer118.2 | - | Persistence | PEN, MET, ER, CIP, LEV | Positive | Negative | Strong | Moderate | 125 | |||
Cure116 | F, 62 | Knee | EPI | 79 | Resolved | PEN | Positive | Negative | Weak | Weak | 5 |
Cure804 | F, 84 | Knee | AHI | 89 | Resolved | ‡ | Positive | Negative | Weak | Weak | 10 |
Cure806 | M, 37 | Knee | EPI | 81 | Resolved | PEN, GEN | Positive | Negative | Strong | Weak | 45 |
Cure111 | M, 69 | Knee | EPI | 82 | Resolved | PEN | Positive | Negative | Strong | Weak | 30 |
Cure112 | F, 83 | Knee | AHI | 90 | Resolved | PEN | Positive | Negative | Negative | Weak | 6 |
Cure208 | M, 53 | Hip | EPI | 93 | Resolved | PEN, ER, CL | Positive | Negative | Negative | Strong | 509 |
Cure807 | F, 63 | Knee | EPI | 57 | Resolved | PEN | Positive | Negative | Strong | Weak | 45 |
Cure808 | F, 72 | Knee | EPI | 100 | Resolved | PEN | Positive | Negative | Strong | Weak | 852 |
Antibiotic Type | Phenotypic Resistance N (%) | Genotypic Resistance N (%) | ||
---|---|---|---|---|
Betalactams | Penicillin Methicillin | 13 (92.9) 1 (7.1) | blaZ mecA | 13 (92.9) 1 (7.1) |
Aminoglycosides | Gentamicin | 3 (21.4) | aac(6′)-aph(2″) aphA ant | 2 (14.3) 0 (0.0) 1 (7.1) |
Fluoroquinolones | Ciprofloxacin Levofloxacin | 3 (21.4) 2 (14.3) | norA gryA mutation (S8AL) grlA mutation (S80F) | 14 (100) 2 (14.3) 3 (21.4) |
Macrolides, lincosamides, streptogramin B | Erythromycin Clindamycin | 2 (14.3)2 (14.3) | erm(A) erm(C) msr(A) | 1 (7.1) 0 (0.0) 1 (7.1) |
Trimethoprim | Cotrimoxazole | 0 (0.0) | dfrA dfrB mutation (2 H31N, 1 F99Y) dfrC | 0 (0.0) 3 (21.4) 0 (0.0) |
Fosfomycin | Fosfomycin | 0 (0.0) | fosB | 5 (35.7) |
Mupirocin | Mupirocin | 0 (0.0) | mupA | 0 (0.0) |
Fusidic acid | Fusidic acid | 0 (0.0) | fusA mutation | 0 (0.0) |
Rifampin | Rifampin | 0 (0.0) | rpoB mutation | 0 (0.0) |
Isolates | Nucleotide Position | Initial Isolate | Relapsing/ Persistent Isolate | Annotation | Type of Mutation | Description (Gene) |
---|---|---|---|---|---|---|
FailRel104 | 82110 | A | C | G57G | SYN | lipoprotein |
126756 | Δ8 bp | 83–90/741 nt | DEL | GntR family regulatory protein | ||
241537–243250 | 4 MBS, 3 NSYN, 5 SYN | staphylocoagulase precursor | ||||
428158–431375 | 6 MBS, 11 NSYN, 4 SYN | exotoxin | ||||
437491–437497 | 3 NSYN | exotoxin5 | ||||
442703, 442706 | SYN, NSYN | exotoxin | ||||
446421–448928 | 5 NSYN, 6 SYN, 1 MBS | lipoprotein | ||||
479985, 479991 | 2 SYN | glutamate synthase, small subunit | ||||
560689 | Δ3 bp | 343–345/1401 nt | DEL | cysteinyl-tRNA synthetase | ||
598737 | T | A | A364A | SYN | serine-aspartate repeat-containing protein D (sdrD) | |
604977 | C | T | D947D | SYN | bone sialoprotein-binding protein | |
842802, 842812 | MBS, SYN | clumping factor A (clfA) | ||||
946908–947417 | 3 SYN, 1 DEL, 1 MBS | transport system extracellular binding lipoprotein | ||||
1059255 | +TGTTGGTTTCGACGGTGT | 1279/3753 nt | INS | bifunctional autolysin precursor | ||
1388164, 1388182 | MBS, SYN | topoisomerase IV subunit A | ||||
1883013 | C | T | A234T | NSYN | serine protease | |
2088541–2088547 | 3SYN | autoinducer sensor protein | ||||
2275393–2275829 | 2 DEL, 4 NSYN, 1 SYN, 1 MBS | hyaluronate lyase precursor 2 | ||||
2464027 | Δ4 bp | 126–129/780 nt | DEL | extracellular solute-binding lipoprotein | ||
2538425–2538596 | 6 SYN, 1 NSYN, 4MBS | lipoprotein | ||||
2557255–2558646 | 2 SYN, 2MBS | fibronectin-binding protein B precursor (fnbB) | ||||
2560605–2562933 | 5 NSYN, 7 SYN, 2 MBS, 2 DEL | fibronectin-binding protein A precursor (fnbA) | ||||
FailRel107 | 915183 | A | G | G139D | NSYN | lpxtg-motif cell wall anchor domain |
1642042 | T | C | Y18Y | SYN | integrase | |
1699959 | A | C | T582T | SYN | penicillin-binding Protein dimerisation domain family | |
FailRel409 | 81598–83027 | 6 NSYN, 6 SYN, 3 MBS | lipoprotein | |||
98820 | G | A | G298G | SYN | immunoglobulin G binding protein A precursor | |
243016 | C | T | N532N | SYN | staphylocoagulase precursor | |
431559, 431562 | 2 NSYN | exotoxin | ||||
598737 | A | T | A364A | SYN | serine-aspartate repeat-containing protein D (sdrD) | |
843649 | G | T | V867V | SYN | clumping factor A (clfA) | |
1059255 | +TGTTGGTTTCGACGGTGT | 1279/3753 nt | INS | bifunctional autolysin precursor | ||
1148233 | +68 bp | 931/939 nt | INS | ribonuclease HIII | ||
1622493, 1622511 | DEL, NSYN | DNA primase | ||||
2088515 | 3 bp→CTC | 610–612/1293 nt | MBS | autoinducer sensor protein | ||
2496948–2497602 | 7 SYN, 1 NSYN, 7MBS | protein flp | ||||
2538455, 2539355 | SYN, MBS, NSYN | exported protein (lipoprotein) | ||||
2560599–2562279 | 5 SYN, 3 NSYN | fibronectin-binding protein A precursor (fnbA) | ||||
2567893–2567901 | 2 SYN, 2 NSYN | MerR family regulatory protein | ||||
2700008, 2700011 | 2 SYN | fibrinogen and keratin-10 binding surface anchored protein | ||||
FailPer401 | 19218 | +G | 874/1968 nt | INS | DHHA1 domain protein | |
103426 | T | A | I503F | NSYN | N-acetyl-ornithine/N-acetyl-lysine deacetylase family protein | |
199157 | Δ131 bp | 730-860/960 nt | DEL | cation diffusion facilitator transporter family protein | ||
1197044 | A | C | K309Q | NSYN | methionyl-tRNA formyltransferase (fmt) | |
1598596 | Δ8 bp | 695-702/1020 nt | DEL | maltose operon transcriptional repressor-like protein | ||
2042765 | Δ107 bp | 1167-1273/1539 nt | DEL | sodium/proline symporter (putP) | ||
2215085 | A | T | N169I | NSYN | ATP synthase F1, gamma subunit (atpG) | |
2397306 | +T | 193/348 nt | INS | transcriptional regulator family protein | ||
FailPer402 | No mutations were found in the strains belonging to the persistent PJI 402. | |||||
FailPer118 | 1696986 | (AATG)3→4 | 11/561 nt | DEL | DNA-3-methyladenine glycosidase |
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Muñoz-Gallego, I.; Meléndez-Carmona, M.Á.; Lora-Tamayo, J.; Garrido-Allepuz, C.; Chaves, F.; Sebastián, V.; Viedma, E. Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection. Antibiotics 2022, 11, 1119. https://doi.org/10.3390/antibiotics11081119
Muñoz-Gallego I, Meléndez-Carmona MÁ, Lora-Tamayo J, Garrido-Allepuz C, Chaves F, Sebastián V, Viedma E. Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection. Antibiotics. 2022; 11(8):1119. https://doi.org/10.3390/antibiotics11081119
Chicago/Turabian StyleMuñoz-Gallego, Irene, María Ángeles Meléndez-Carmona, Jaime Lora-Tamayo, Carlos Garrido-Allepuz, Fernando Chaves, Virginia Sebastián, and Esther Viedma. 2022. "Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection" Antibiotics 11, no. 8: 1119. https://doi.org/10.3390/antibiotics11081119
APA StyleMuñoz-Gallego, I., Meléndez-Carmona, M. Á., Lora-Tamayo, J., Garrido-Allepuz, C., Chaves, F., Sebastián, V., & Viedma, E. (2022). Microbiological and Molecular Features Associated with Persistent and Relapsing Staphylococcus aureus Prosthetic Joint Infection. Antibiotics, 11(8), 1119. https://doi.org/10.3390/antibiotics11081119