The DOI matches its Crossref record; 239 of the 242 references it cites were found in a registry or an index; none of the 155 sources its claims cite is checked for support yet.
Molecular Mechanisms of Drug Resistance in Staphylococcus aureus
Open accessAbstract
This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.
Overview
CoChat Summary
TL;DR
This review summarizes molecular mechanisms of drug resistance in *Staphylococcus aureus*, covering beta-lactams, glycopeptides, oxazolidinones, MLS-B, aminoglycosides, fluoroquinolones, tetracyclines, mupirocin, fusidic acid, daptomycin, and other agents. It emphasizes SCC*mec*/*mec*-mediated methicillin resistance, VanA-mediated glycopeptide resistance, and mobile genetic elements as drivers of multidrug resistance.
Key findings
- Methicillin resistance is chiefly mediated by PBP2A encoded by *mec* genes within SCC*mec* cassettes; 14 major SCC*mec* types have been described, ranging from 21 to 82 thousand nucleotides, with *mecA*, *mecC*, and other *mec* variants distributed across staphylococci.
- Beta-lactam resistance also involves beta-lactamases (*blaZ*) and rare PBP mutations; a *mecA*-negative CRB strain had ceftobiprole MIC = 128 mg/L, ceftriaxone MIC = 256 mg/L, cefazolin MIC > 256 mg/L, nafcillin MIC = 128 mg/L, ampicillin MIC = 256 mg/L, and cefoxitin MIC = 8 mg/L.
- Glycopeptide resistance via the VanA operon in Tn*1546* confers vancomycin MIC 64–1024 mg/L and teicoplanin MIC 16–512 mg/L; only about a dozen VRSA strains with VanA have been described. In 187 MRSA strains from 41 Spanish hospitals, vancomycin tolerance was 9.6% and teicoplanin tolerance 21.9%.
- Aminoglycoside resistance commonly involves AAC(6′)-Ie/APH(2″)-Ia, the only enzyme known in *S. aureus* to determine gentamicin resistance; gentamicin MICs ranged from 8 mg/L to >1024 mg/L (MIC50 128 mg/L, MIC90 512 mg/L), and tobramycin MICs ranged from 8 to 256 mg/L (MIC50 32 mg/L, MIC90 64 mg/L).
Methods
- Design: narrative review of published literature on molecular resistance mechanisms in *S. aureus*; no systematic review protocol or primary experimental study is described.
- Data or sample: Not stated in the paper; the text cites clinical isolates, strains, plasmids, transposons, integrons, and SCC*mec* elements from prior studies.
- Main analysis: descriptive synthesis organized by antibiotic class and molecular epidemiology, including referenced tables and figures on SCC*mec* types, *mec*/*ccr* complexes, and MRSA clones.
Limitations
- The paper states no limitations section.
- Evident: as a narrative review, it lacks systematic search, inclusion criteria, and formal risk-of-bias assessment.
- Evident: it presents no new primary data and relies on previously published studies; several tables and figures are referenced but not included in the provided text, limiting verification of clone and SCC*mec* details.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
0 Valid · 6 Not valid · 95 Not checked · 5 Own results and interpretations
None of the sources cited for this claim have been checked yet.
In the paper
“In 2006, the first class I integrons, previously described in Gram-negative bacteria, were detected in staphylococci, initially found in coagulase-negative staphylococci and later in S. aureus.”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 1. Introduction
What the sources say
- Not checked yetcites [8] Shi, 2006, Unnoticed spread of class 1 integrons in gram-positive clinical strains isolated in Guangzhou, China, Microbiol. Immunol. source
- Not checked yetcites [9] Xu, 2008, First confirmation of integron-bearing methicillin-resistant Staphylococcus aureus, Curr. Microbiol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The cassette genes functioning in these integrons that determine resistance to streptomycin (aadA2, aadA5), chloramphenicol (cmlA1) and trimethoprim (dfrA12, dfr17) have also been described [8,9].”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 1. Introduction
What the sources say
- Not checked yetcites [8] Shi, 2006, Unnoticed spread of class 1 integrons in gram-positive clinical strains isolated in Guangzhou, China, Microbiol. Immunol. source
- Not checked yetcites [9] Xu, 2008, First confirmation of integron-bearing methicillin-resistant Staphylococcus aureus, Curr. Microbiol. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, the mere presence of a pathogenicity factor gene does not always equate to its expression, which is subject to one or more regulatory systems present in the bacterial cell, such as the Agr/Sar system [10]”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 1. Introduction
What the sources say
- Not checked yetcites [10] Butrico, C.E., and Cassat, J.E. (2020). Quorum sensing and toxin production in Staphylococcus aureus osteomyelitis: Pathogenesis and paradox. Toxins, 12. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The mecA gene has been detected in S. aureus, S. pseudintermedius, Mammallicoccus fleuretti (former name Staphylococcus fleuretti), Mammallicoccus vitulinus (former name Staphylococcus vitulinus), Mammallicoccus sciuri (former name Staphylococcus sciuri) and in many other species of the genus Staphylococcus currently comprising 64 species [21].”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 2. Resistance to Beta-Lactam Antibiotics > 2.2. PBP2A Synthesis (Methicillin-Resistance)
What the sources say
- Not checked yetcites [21] (2022, February 03). Taxonomy Browser (Staphylococcus), Available online: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Single strains of the so-called BORSA (borderline oxacillin-resistant S. aureus) have been described, in which the synthesized beta-lactamase had an extended spectrum and conditioned an oxacillin MIC of 4–8 mg/L [15].”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 2. Resistance to Beta-Lactam Antibiotics > 2.1. Synthesis of Beta-Lactamases
What the sources say
- Not checked yetcites [15] Balslev, 2005, An outbreak of borderline oxacillin-resistant Staphylococcus aureus (BORSA) in a dermatological unit, Microb. Drug Resist. source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
57 more claims
Create a free account to see all 106 claims and to verify the 155 references still open.
- It may state two separate claims as one. 35
- Probably not a substantial claim. 15
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In MRSA, PBP2a maintains transpeptidase activity even under β-lactam exposure, enabling cross-linking of pentaglycan bridges between peptidoglycan chains [9,198].”
From Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms (2025) · cites this paper as [9]
In the citing paper
“Resistance extends to all β-lactams except ceftobiprole and ceftaroline, which retain activity against PBP2a [9,203].”
From Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms (2025) · cites this paper as [9]
In the citing paper
“Constitutive expression occurs in strains with ΔmecR1-mecA deletions [9,202].”
From Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms (2025) · cites this paper as [9]
In the citing paper
“The mecA gene, located on the staphylococcal chromosomal cassette mec (SCCmec), produces PBP2a (also termed PBP2′), a 668-amino-acid protein that replaces the transpeptidase function of native PBPs inhibited by β-lactams [9,195,197].”
From Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms (2025) · cites this paper as [9]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 12. Other Antibiotics > 12.3. Resistance to Chloramphenicol
“A mutation in the rpoB gene (A1345G; substitution in RpoB protein D449N) was also described, conditioning the resistance of S. aureus strain to chloramphenicol (MIC-128 mg/L) and intermediate to oxazolidinones [94].”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 4. Resistance to Oxazolidinones
“A mutation in the rpoB gene (A1345G; substitution in the RpoB protein D449N) was also described, which determines the resistance of S. aureus strain to linezolid (MIC = 8 mg/L) and tedizolid (MIC = 4 mg/L), chloramphenicol (MIC-128 mg/L), medium sensitivity to quinupristin/dalphopristin (MIC-2 mg/L) [94].”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 5. Resistance to Macrolides, Lincosamides, Ketolides and Streptogramins B
“VgbA, VgbB, inactivating streptogramin B lyases”
§ Molecular Mechanisms of Drug Resistance in Staphylococcus aureus > 12. Other Antibiotics > 12.1. Resistance to Streptogramins A and Quinupristin-Dalfopristin
“Resistance to streptogramins A in S. aureus may result from the production of enzymes that inactivate streptogramins A such as Vat acetyltransferases encoded by the plasmid genes vatA [179], vatB located in the Tn5406 transposon [180,181], vatC [130], vatD, vatE [130] or Vgb lyases encoded by the vgb(A) and vgb(B) genes [131].”
Citations
Cites
Updated Functional Classification of β-Lactamases
Bush, K., & Jacoby, G. A. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01009-09 · Cited by 2,367
Antimicrobial Resistance in ESKAPE Pathogens
De Oliveira, D. M. P., Forde, B. M., Kidd, T. J., Harris, P. N. A., Schembri, M. A., Beatson, S. A., Paterson, D. L., & Walker, M. J. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00181-19 · Cited by 2,078
beta-Lactamases in laboratory and clinical resistance
Livermore, D. M. (1995) · Clinical Microbiology Reviews · doi:10.1128/cmr.8.4.557 · Cited by 1,779
Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology
Lakhundi, S., & Zhang, K. (2018) · Clinical Microbiology Reviews · doi:10.1128/cmr.00020-18 · Cited by 1,637
Antimicrobial resistance: the example of Staphylococcus aureus
Lowy, F. D. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18535 · Cited by 1,445
Oliveira, D. C., & Lencastre, H. D. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.7.2155-2161.2002 · Cited by 1,343
Vancomycin Resistance in Gram-Positive Cocci
Courvalin, P. (2006) · Clinical Infectious Diseases · doi:10.1086/491711 · Cited by 1,028
Kondo, Y., Ito, T., Ma, X. X., Watanabe, S., Kreiswirth, B. N., Etienne, J., & Hiramatsu, K. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00165-06 · Cited by 965
Ito, T., Katayama, Y., Asada, K., Mori, N., Tsutsumimoto, K., Tiensasitorn, C., & Hiramatsu, K. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.5.1323-1336.2001 · Cited by 963
García-Álvarez, L., Holden, M. T., Lindsay, H., Webb, C. R., Brown, D. F., Curran, M. D., Walpole, E., Brooks, K., Pickard, D. J., Teale, C., et al. (2011) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(11)70126-8 · Cited by 939
Research works printed but not linked: 1
- (2022, February 03). Taxonomy Browser (Staphylococcus), Available online: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi.
Cited by
Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms
Touaitia, R., Mairi, A., Ibrahim, N. A., Basher, N. S., Idres, T., & Touati, A. (2025) · Antibiotics · doi:10.3390/antibiotics14050470 · Cited by 273
Mechanism of staphylococcal resistance to clinically relevant antibiotics
Brdová, D., Ruml, T., & Viktorová, J. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101147 · Cited by 135
Bashabsheh, R. H. F., Al-Fawares, O., Natsheh, I. Y., Bdeir, R., Al-Khreshieh, R. O., & Bashabsheh, H. H. F. (2023) · Pathogens and Global Health · doi:10.1080/20477724.2023.2285187 · Cited by 100
Evaluation of Antibiotic Resistance Mechanisms in Gram-Positive Bacteria
Rajput, P., Nahar, K. S., & Rahman, K. M. (2024) · Antibiotics · doi:10.3390/antibiotics13121197 · Cited by 98
Qiu, M., Zheng, M., Zhang, J., Yang, X., Zhang, Y., Zhang, W., Man, C., Zhao, Q., & Jiang, Y. (2023) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2023.117258 · Cited by 76
Metadata
- Authors
- Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., & Marusza, W.
- Affiliations
- Department of Dermatology, Immunodermatology and Venereology, Medical University of Warsaw, Koszykowa 82a, 02-008 Warsaw, Poland
- Academy of Face Sculpting, Jana Kazimierza 11B, 01-248 Warsaw, Poland
- Corresponding author
- Marusza, Wojciech
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2022-07-22
- Volume
- 23
- Issue
- 15
- Pages
- 8088
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9332259
- OpenAlex
- W4286587477
- Cited by
- 412
- References
- 242
- Citations by year
- 2026: 103 · 2025: 122 · 2024: 114 · 2023: 59 · 2022: 13
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Staphylococcus aureus, antibiotic resistance, methicillin-resistant Staphylococcus aureus, beta-lactam resistance, mec gene, glycopeptide resistance, vancomycin resistance, oxazolidinone resistance, linezolid, aminoglycoside resistance, fluoroquinolone resistance, tetracycline resistance, mupirocin resistance, fusidic acid resistance, daptomycin resistance, molecular epidemiology, virulence genes
- MeSH terms
- Aminoglycosides, Anti-Bacterial Agents, Drug Resistance, Humans, Microbial Sensitivity Tests, Staphylococcal Infections, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-15, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-15 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Molecular Mechanisms of Drug Resistance in Staphylococcus aureus. https://app.cochat.ai/papers/10.3390/ijms23158088
- The paper
- Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., & Marusza, W. (2022). Molecular Mechanisms of Drug Resistance in Staphylococcus aureus. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms23158088
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
