Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review
Abstract
:1. Introduction
2. Results
2.1. Binding Site Alterations
2.1.1. Van Genes
Ref. | Gene | Genetic Mechanism (If Described) | Encoded Protein | Function | Proposed Mechanism of Resistance |
---|---|---|---|---|---|
[29] | agrD1 | Overexpression | Accessory gene regulator D1 (AgrD1) | Quorum sensing generation/modulation | Unknown |
[27] | cd2068 | Upregulation | CD2068 | ABC transporter pump | Drug efflux* |
[25] | cd3659 | Mutation (Gly982Thr) | DNA exonuclease/phosphodiesterase | -- | Unknown |
[28] | cdtA | Presence ** | Toxin A (TcdA) | Enterotoxin | No impact |
[28] | cdtB | Presence ** | Toxin B (TcdB) | Cytotoxin | No impact |
[28] | cwlD | Presence ** | N-acetylmuramoyl-L-alanine amidase | Spore germination | No impact |
[24,28,29] | cwp84 | Overexpression | Cysteine protease (Cwp84) | Surface layer protein maturation/adhesion/biofilm regulation | Biofilm production |
[28] | fliC | Presence ** | Flagellin (FliC) | Adhesion/biofilm regulation | Biofilm production |
[28,29] | luxS | Presence ** | LuxS | Autoinducer-2 synthesis/quorum sensing modulation/biofilm regulation | Biofilm production |
[26] | pX18-498_006 *** | Presence | N-acetylmuramoyl-L-alanine amidase | Cell wall integrity | Unknown |
[25] | sdaB/cd3222 | Mutation (Ala295 deletion) | L-serine deaminase | -- | Unknown |
[29] | sigH | Overexpression | Sigma factor (SigH) | Sporulation regulation | Biofilm production |
[28] | sleC | Presence ** | SleC | Spore germination | Biofilm production |
[29] | slpA | Presence | S-layer protein (SlpA) | Surface layer composition/ adhesion/biofilm regulation | No impact |
[28,29] | spo0A | Overexpression | Spo0A | Sporulation/biofilm regulation | Biofilm production |
2.1.2. MurG
2.2. Plasmid Acquisition of N-Acetylmuramoyl-L-Alanine
2.3. Efflux Pumps
2.4. RNA Polymerase Mutations
2.5. Biofilm Production
2.5.1. Surface Factors Involved in Biofilm Formation
2.5.2. Sporulation and Germination
2.5.3. Quorum Sensing
3. Materials and Methods
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Ref. | No. Isolates † | Strain Origin | Ribotype | ST Type | Other | Gene (Mutation, If Known) | VAN MIC (mg/L) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
vanG/vanSR | vanA | vanB | vanW | vanZ | murG | rpoC | |||||||
[22] | 4 | Clinical | 012 | 54 | NAPCR1 | vanG | 4 | ||||||
[23] * | 1 | Laboratory | 027 | 1 | WS2/ R20291 | vanS (Arg314Leu) | 8 | ||||||
1 | Laboratory | 027 | 1 | WS4/ R20291 | vanS (Gly319Asp) | 16 | |||||||
1 | Clinical | 027 | 1 | MT1470 | vanS (Ser313Phe) | 8 | |||||||
1 | Clinical | 027 | 1 | MT5006 | vanS (Thr349Ile) | 8 | |||||||
9 | Clinical | 027 | 1 | see note ‡ | vanR (Thr115Ala) | 4–8 ‡ | |||||||
[24] | 1 | Clinical | 35 | vanA | vanW | 4 | |||||||
1 | Clinical | 014-020 | 2 | vanB | 8 | ||||||||
1 | Clinical | 42 | vanB | 4 | |||||||||
1 | Clinical | 67 | vanB | vanW | >16 | ||||||||
1 | Clinical | 012 | 54 | vanW | vanZ | 4 | |||||||
[25] * | 1 | Laboratory | 087 | NB95013/ATCC 43255 | murG/cd2725 (Pro108Leu) | 16 | |||||||
1 | Laboratory | NB95026 | rpoC/cd0067 (Gly733Thr) | 16 |
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Eubank, T.A.; Gonzales-Luna, A.J.; Hurdle, J.G.; Garey, K.W. Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review. Antibiotics 2022, 11, 258. https://doi.org/10.3390/antibiotics11020258
Eubank TA, Gonzales-Luna AJ, Hurdle JG, Garey KW. Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review. Antibiotics. 2022; 11(2):258. https://doi.org/10.3390/antibiotics11020258
Chicago/Turabian StyleEubank, Taryn A., Anne J. Gonzales-Luna, Julian G. Hurdle, and Kevin W. Garey. 2022. "Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review" Antibiotics 11, no. 2: 258. https://doi.org/10.3390/antibiotics11020258
APA StyleEubank, T. A., Gonzales-Luna, A. J., Hurdle, J. G., & Garey, K. W. (2022). Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review. Antibiotics, 11(2), 258. https://doi.org/10.3390/antibiotics11020258