# sul1 (Dihydropteroate Synthase): Sulfonamide Resistance and Folate Biosynthesis Inhibition


## Key Takeaways

- The *sul1* gene encodes an acquired, horizontally transferable dihydropteroate synthase (DHPS) that confers high-level sulfonamide resistance by possessing a modified pABA-binding pocket with reduced affinity for sulfonamides while retaining catalytic activity with the natural substrate.
- *sul1* is predominantly found on mobile genetic elements, most notably class 1 integrons and associated transposons (e.g., Tn21), facilitating its widespread dissemination across diverse bacterial species and making it a key marker for anthropogenic pollution and AMR surveillance.
- Its expression is primarily driven by the integron-associated *Pc* promoter, with variants like *Pc*S conferring higher expression levels and thus higher sulfonamide minimum inhibitory concentrations (MICs), and it frequently co-occurs with other resistance genes like *dfrA* and *bla*NDM on multidrug resistance plasmids.
- The presence of *sul1* is clinically significant in pathogens such as *Escherichia coli*, *Acinetobacter baumannii*, and *Stenotrophomonas maltophilia*, contributing to treatment failures for infections like UTIs and pneumonia, and its detection via PCR or WGS is crucial for AMR surveillance.
- Strategies to overcome *sul1*-mediated resistance include developing novel DHPS inhibitors that exploit structural differences between native FolP and Sul1, inhibiting integron function, or employing anti-plasmid approaches and CRISPR-Cas systems for targeted gene cleavage.

---

## Executive Summary & Key Metadata

The `sul1` gene encodes an alternative dihydropteroate synthase (DHPS; EC 2.5.1.15), a bacterial enzyme that catalyzes the condensation of *p*-aminobenzoic acid (pABA) with 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPP) to form 7,8-dihydropteroate, an essential intermediate in the *de novo* folate biosynthesis pathway. Unlike the chromosomal housekeeping `folP` gene, which encodes the native DHPS, `sul1` is an acquired, horizontally transferable resistance determinant that confers high-level resistance to sulfonamide antibiotics. Sulfonamides are competitive inhibitors of pABA binding to DHPS; the Sul1 protein possesses a modified pABA-binding pocket that drastically reduces affinity for sulfonamides while retaining catalytic activity with the natural substrate [1][2].

The clinical and environmental significance of `sul1` is profound. It is the most frequently detected sulfonamide resistance gene in Gram-negative bacteria, often associated with class 1 integrons and transposons (e.g., Tn21, Tn402), which facilitate its dissemination across diverse bacterial species [3][4][5]. The gene is a marker for anthropogenic pollution and antimicrobial resistance (AMR) surveillance in environmental microbiology, wastewater treatment, and clinical diagnostics [6][7][8].

| **Attribute** | **Value** |
|---|---|
| **HGNC Symbol** | sul1 (bacterial gene; no human ortholog) |
| **UniProt Accession** | P0C017 |
| **Representative PDB ID** | 3TYA |
| **Chromosomal Locus** | Typically plasmid-borne or integron-associated; not chromosomal in most clinical isolates |
| **Primary Molecular Function** | Alternative dihydropteroate synthase (DHPS); sulfonamide-resistant form of FolP |
| **Disease & Pathology Associations** | Antimicrobial resistance (AMR) in urinary tract infections (UTIs), bacteremia, pneumonia, and nosocomial infections; co-occurrence with other resistance genes (e.g., *dfrA*, *bla*NDM) |
| **Enzyme Commission Number** | EC 2.5.1.15 |
| **Substrate** | pABA + 6-hydroxymethyl-7,8-dihydropterin pyrophosphate |
| **Inhibitor** | Sulfonamides (e.g., sulfamethoxazole, sulfamethazine, sulfadiazine) |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Genomic Context and Mobile Genetic Elements

The `sul1` gene is rarely found on the bacterial chromosome. Instead, it is almost exclusively localized on mobile genetic elements (MGEs), most notably **class 1 integrons**. These integrons are genetic platforms that capture and express gene cassettes via site-specific recombination. The canonical structure of a class 1 integron includes:

- **5' conserved segment (5'-CS)**: Contains the *intI1* gene encoding integrase, the *attI1* recombination site, and the *Pc* promoter that drives expression of downstream gene cassettes.
- **3' conserved segment (3'-CS)**: Contains *qacEΔ1* (a truncated quaternary ammonium compound resistance gene) and *sul1* [3][4][9].

The *sul1* gene is located in the 3'-CS, downstream of *qacEΔ1*, and is transcribed from the *Pc* promoter located in the 5'-CS. This genetic arrangement ensures constitutive expression of *sul1* when the integron is active. The close physical linkage between *sul1* and *qacEΔ1* is a hallmark of class 1 integrons and is frequently used as a molecular marker for these elements in environmental and clinical surveillance [3][5].

### 1.2 Plasmid Localization and Horizontal Gene Transfer

Beyond integrons, *sul1* is often embedded in larger transposons (e.g., Tn21, Tn402) that reside on conjugative plasmids. These plasmids belong to various incompatibility (Inc) groups, including IncFII, IncHI1, IncL/M, and IncA/C, which are commonly associated with multidrug resistance (MDR) in Enterobacteriaceae [10][11][12]. The plasmid-borne nature of *sul1* facilitates its rapid horizontal transfer between species and genera, contributing to the global dissemination of sulfonamide resistance.

For example, a study by Yu et al. (2020) characterized two NDM-1-producing Enterobacteriaceae strains (*Raoultella ornithinolytica* and *Enterobacter cloacae*) isolated from a single patient, and identified a novel plasmid that carried both *bla*NDM-1 and *sul1*, demonstrating *in vivo* plasmid transfer via conjugation [10]. Similarly, Hishinuma et al. (2013) sequenced an IncFII plasmid from *Klebsiella pneumoniae* that harbored *sul1* alongside multiple other resistance determinants, highlighting the role of such plasmids in MDR dissemination [12].

### 1.3 Promoter Architecture and Transcriptional Regulation

The expression of *sul1* is primarily driven by the integron-associated *Pc* promoter. Two variants of *Pc* exist—*Pc*S (strong) and *Pc*W (weak)—which differ by a single nucleotide polymorphism at position −35 relative to the transcription start site. The *Pc*S variant confers higher expression levels of downstream genes, including *sul1*, and is associated with higher sulfonamide minimum inhibitory concentrations (MICs) [3][4].

In addition to *Pc*, a second promoter, *P2*, may be present in some class 1 integrons, further enhancing *sul1* transcription. The presence of *P2* is associated with a 5-bp insertion in the 5'-CS and is more common in clinical isolates than in environmental ones [3].

### 1.4 Isoforms and Variants

Unlike eukaryotic genes, *sul1* does not undergo alternative splicing. However, multiple allelic variants of *sul1* exist, differing by single nucleotide polymorphisms (SNPs) that may alter the amino acid sequence. These variants are grouped into two main classes: *sul1* and *sul1*-like. The *sul1*-like variants share >95% nucleotide identity with the canonical *sul1* but may exhibit minor differences in the promoter region or coding sequence [4][5].

A related but distinct gene, *sul4*, was recently discovered in marine bacteria and is not associated with mobile genetic elements, suggesting a different evolutionary origin [6][3]. The *sul4* gene shares low sequence identity with *sul1* (~40%) but confers a similar resistance phenotype [6].

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Overall Fold and Domain Organization

The Sul1 protein is a homodimeric enzyme belonging to the **nucleoside diphosphate transferase (NDT) superfamily**, which also includes the chromosomal FolP. The monomer consists of a single α/β domain with a central **seven-stranded β-sheet** flanked by α-helices. The overall fold is reminiscent of the **TIM barrel** but is more accurately described as a **Rossmann-like fold** [1].

The protein can be divided into two functional regions:

1. **N-terminal pABA-binding domain (residues 1–120)**: This region forms a deep pocket that accommodates pABA. In Sul1, several key residues in this pocket are substituted compared to FolP, reducing the binding affinity for sulfonamides.
2. **C-terminal DHPP-binding domain (residues 121–280)**: This region binds the pyrophosphate moiety of DHPP and contains the catalytic residues involved in the condensation reaction.

### 2.2 Catalytic Site and Key Residues

The catalytic mechanism of DHPS involves a nucleophilic attack by the amino group of pABA on the pyrophosphate carbon of DHPP, releasing inorganic pyrophosphate. In FolP, the catalytic residues include:

- **Asp-96** (in *E. coli* FolP): Coordinates the pterin ring of DHPP.
- **Lys-221**: Stabilizes the pyrophosphate leaving group.
- **Arg-255**: Binds the carboxylate group of pABA.

In Sul1, the corresponding residues are conserved, but the pABA-binding pocket is enlarged due to substitutions at positions that line the pocket. For example, a phenylalanine residue in FolP (Phe-28) that forms a π-stacking interaction with pABA is replaced by a smaller residue (e.g., leucine or valine) in Sul1, creating additional space that accommodates the bulky sulfonamide group but reduces binding affinity [1].

### 2.3 Structural Comparison with FolP

High-resolution crystal structures of Sul1 (e.g., PDB: 3TYA) and FolP (e.g., PDB: 1AJZ) reveal that the overall folds are nearly superimposable, with a root-mean-square deviation (RMSD) of ~1.5 Å over Cα atoms. However, the electrostatic surface potential of the pABA-binding pocket differs significantly. In FolP, the pocket is narrow and lined with hydrophobic residues that tightly bind pABA. In Sul1, the pocket is wider and more hydrophilic, reducing the van der Waals contacts with sulfonamides [1].

A key structural feature of Sul1 is the presence of a **flexible loop** (residues 45–60) that undergoes a conformational change upon substrate binding. This loop is shorter in Sul1 than in FolP, which may contribute to the reduced affinity for sulfonamides by altering the dynamics of the binding pocket [1].

### 2.4 Interactive 3D Visualizer

[Interactive 3D Protein Visualizer: Load sul1 (PDB: 3TYA)](/tools/protein-structure-viewer?source=direct&pdbId=3TYA)

The interactive visualizer allows users to explore the Sul1 structure in three dimensions, highlighting the pABA-binding pocket, catalytic residues, and dimer interface. Users can overlay the structure with sequence annotations and mutation data from ClinVar and other databases.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The Folate Biosynthesis Pathway

The primary biological role of Sul1 is to replace the native DHPS (FolP) in the **de novo folate biosynthesis pathway**. Folate (vitamin B9) is an essential cofactor for the synthesis of nucleic acids, amino acids, and other metabolites. Bacteria synthesize folate *de novo*, whereas humans obtain it from dietary sources. This metabolic difference is the basis for the selective toxicity of sulfonamides.

The pathway proceeds as follows:

1. **GTP cyclohydrolase I (FolE)** converts GTP to 7,8-dihydroneopterin triphosphate.
2. **Dihydroneopterin aldolase (FolB)** and **6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (FolK)** convert the intermediate to DHPP.
3. **Dihydropteroate synthase (FolP or Sul1)** condenses DHPP with pABA to form 7,8-dihydropteroate.
4. **Dihydrofolate synthase (FolC)** adds a glutamate residue to form dihydrofolate.
5. **Dihydrofolate reductase (FolA)** reduces dihydrofolate to tetrahydrofolate, the active cofactor.

Sulfonamides competitively inhibit step 3 by mimicking pABA and binding to the DHPS active site. In Sul1, the modified binding pocket reduces sulfonamide affinity by 100- to 1,000-fold, allowing the enzyme to continue catalyzing the condensation reaction even in the presence of therapeutic concentrations of sulfonamides [13][2].

### 3.2 Protein-Protein Interactions

Sul1 does not participate in complex signaling cascades; rather, it functions as a metabolic enzyme. However, its expression is tightly linked to the integron machinery. The integrase IntI1, encoded by *intI1*, catalyzes the excision and integration of gene cassettes at the *attI1* site. While Sul1 itself does not interact with IntI1, the co-expression of *sul1* and *intI1* on the same integron ensures that the resistance phenotype is maintained even when other cassettes are excised [3][9].

### 3.3 Fitness Costs and Compensatory Evolution

The acquisition of *sul1* imposes a fitness cost on the host bacterium, as the expression of an additional membrane-associated protein (in some contexts) or the metabolic burden of plasmid maintenance can reduce growth rate. However, compensatory mutations in the host genome or in the plasmid can mitigate these costs over time [14].

A study by Jiang et al. (2024) assessed the *in vivo* fitness of *sul* gene-dependent sulfonamide-resistant *E. coli* in a murine gut model. They found that *sul1*-carrying strains exhibited a high fitness cost in the absence of sulfonamide pressure, but this cost was reduced in the presence of the antibiotic, suggesting that the resistance phenotype is maintained by selection [14].

### 3.4 Mermaid Diagram: Sulfonamide Resistance Mechanism

```mermaid
flowchart TD
    A["Sulfonamide antibiotic"] -->|"Competitive inhibition"| B["Native DHPS (FolP)"]
    B -->|"Blocked"| C["No dihydropteroate synthesis"]
    C --> D["Folate depletion"]
    D --> E["Bacterial cell death"]

    A -->|"Reduced binding"| F["Sul1 (alternative DHPS)"]
    F -->|"Active"| G["Dihydropteroate synthesis"]
    G --> H["Folate synthesis continues"]
    H --> I["Bacterial survival and growth"]

    J["Class 1 integron"] -->|"Contains"| K["sul1 gene"]
    K -->|"Expression"| F
    J -->|"Contains"| L["intI1 gene"]
    L -->|"Encodes"| M["Integrase IntI1"]
    M -->|"Captures cassettes"| N["Gene cassette array"]
    N -->|"May include"| O["Other resistance genes e.g., dfrA"]
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Mutations in *sul1* and Their Functional Consequences

While *sul1* itself is a resistance gene, mutations within its coding sequence can further modulate the level of sulfonamide resistance or alter substrate specificity. However, because *sul1* is already highly resistant to sulfonamides, most mutations do not confer additional clinical benefit. Instead, mutations in the promoter region (e.g., in *Pc*) are more clinically relevant, as they affect gene expression levels [3][4].

### 4.2 Co-occurrence with Other Resistance Genes

The clinical significance of *sul1* is amplified by its frequent co-occurrence with other resistance genes on the same mobile genetic element. Common co-resident genes include:

- ***dfrA***: Encodes dihydrofolate reductase, conferring resistance to trimethoprim. The combination of *sul1* and *dfrA* confers resistance to co-trimoxazole (trimethoprim-sulfamethoxazole), a commonly used combination therapy [13][15][16].
- ***bla*NDM**: Encodes New Delhi metallo-β-lactamase, conferring resistance to carbapenems. Plasmids carrying both *bla*NDM and *sul1* have been reported in clinical isolates [10][12].
- ***qacEΔ1***: Encodes a truncated efflux pump that confers resistance to quaternary ammonium compounds, often used as disinfectants [3].

### 4.3 Clinical Differentials and Disease Associations

The presence of *sul1* is a marker for MDR in several clinically significant pathogens:

- ***Escherichia coli***: Uropathogenic *E. coli* (UPEC) strains carrying *sul1* are associated with UTIs that are resistant to first-line antibiotics, including co-trimoxazole [17][18].
- ***Acinetobacter baumannii***: *sul1* is frequently detected in MDR *A. baumannii* isolates, contributing to the limited therapeutic options for infections caused by this pathogen [19][20].
- ***Stenotrophomonas maltophilia***: *sul1* is a key determinant of resistance to co-trimoxazole, the first-line therapy for *S. maltophilia* infections [21][22].
- ***Salmonella enterica***: *sul1* is prevalent in *Salmonella* isolates, particularly those associated with foodborne outbreaks [5][11][23].
- ***Shigella flexneri***: The presence of *sul1* correlates with resistance to sulfamethoxazole-trimethoprim in *S. flexneri* isolates [15].

### 4.4 Detection and Surveillance

The detection of *sul1* is routinely performed using PCR, quantitative PCR (qPCR), and whole-genome sequencing (WGS). [Loop-mediated isothermal amplification](/knowledge/diagnostics/molecular/lamp-assay-rapid-detection-african-swine-fever-virus-oral-fluids) (LAMP) has also been developed for rapid, point-of-care detection of *sul1* in clinical and environmental samples [21]. The gene is a key target in AMR surveillance programs, as its presence indicates prior exposure to sulfonamides and the potential for co-selection of other resistance determinants [7][8].

---

## 5. Host-Pathogen & Viral Interactions (If Applicable)

### 5.1 Bacterial Interactions

Sul1 does not directly interact with host cells or viral proteins. However, its presence on mobile genetic elements has indirect effects on host-pathogen interactions. For example, the co-selection of *sul1* with disinfectant resistance genes (*qacEΔ1*) can lead to the survival of MDR pathogens in healthcare settings, where disinfectants are routinely used [3].

### 5.2 Environmental Reservoirs and the Microbiome

The *sul1* gene is widely distributed in environmental microbiomes, including soil, water, and wastewater. Its presence in these environments is a marker for anthropogenic pollution, as sulfonamides are extensively used in agriculture and human medicine [6][7][8]. The gene can be transferred from environmental bacteria to human pathogens via horizontal gene transfer, contributing to the global AMR crisis [3][4].

### 5.3 Viral Interactions

There are no known direct interactions between Sul1 and viral proteins. However, bacteriophages can act as vehicles for the horizontal transfer of *sul1* via transduction, although this mechanism is less common than conjugation for this gene [3].

---

## 6. [Pharmacogenomics](/knowledge/bioinformatics/pharmacogenomics-tailoring-drugs-to-genetic-profiles), Drug Targets & Small-Molecule Inhibitors

### 6.1 Sulfonamide Antibiotics

Sulfonamides are the primary drugs affected by *sul1*. These include:

- **Sulfamethoxazole**: Often combined with trimethoprim (co-trimoxazole) for synergistic activity.
- **Sulfamethazine**: Used in veterinary medicine.
- **Sulfadiazine**: Used in combination with pyrimethamine for [toxoplasmosis](/knowledge/parasites/pet-parasites/toxoplasmosis-feline-transmission-public-health-clinical-management).
- **Sulfadimethoxine**: Used in veterinary medicine.

The presence of *sul1* confers high-level resistance to all these agents, rendering them ineffective for treating infections caused by *sul1*-positive bacteria [13][2].

### 6.2 Investigational Strategies to Overcome Sul1-Mediated Resistance

Given the clinical importance of sulfonamide resistance, several strategies are being explored to overcome Sul1-mediated resistance:

1. **Novel DHPS Inhibitors**: [Structure-based drug design](/knowledge/bioinformatics/structure-based-drug-design-bioinformatics) aims to develop inhibitors that bind to both FolP and Sul1 with high affinity. By exploiting the structural differences between the two enzymes, it may be possible to design compounds that are not subject to Sul1-mediated resistance [1].
2. **Inhibitors of Integron Function**: Since *sul1* is often located on integrons, inhibiting the integrase IntI1 could prevent the spread of *sul1* and other resistance genes [3].
3. **Anti-Plasmid Approaches**: Compounds that inhibit plasmid replication or conjugation could reduce the dissemination of *sul1* [10][12].
4. **CRISPR-Cas Systems**: Sequence-specific nucleases could be used to target and cleave *sul1* in bacterial populations, sensitizing them to sulfonamides [1].

### 6.3 Selectable Marker in Biotechnology

Beyond its clinical relevance, *sul1* has been adapted as a selectable marker in genetic engineering. For example, Borges-Rodríguez et al. (2026) evaluated *sul1* as a novel selectable marker for the unicellular red alga *Cyanidioschyzon merolae*, demonstrating its utility in transformation experiments [24]. The gene's ability to confer sulfonamide resistance makes it a convenient tool for selecting transformed cells in organisms that are naturally sensitive to sulfonamides.

---

## 7. Bioinformatic Resources & Database Accessions

The following table provides key database accessions and resources for *sul1* and its protein product.

| **Database** | **Accession / Identifier** | **Description** |
|---|---|---|
| **NCBI Gene** | 57791831 (example) | Gene record for *sul1* |
| **NCBI Nucleotide** | Various (e.g., JQ364967) | Nucleotide sequences of *sul1* from different isolates |
| **UniProt** | P0C017 | Protein sequence and functional annotations |
| **RCSB PDB** | 3TYA | Crystal structure of Sul1 |
| **Gene Ontology (GO)** | GO:0004156 (dihydropteroate synthase activity) | Molecular function |
| **GO** | GO:0046656 (folic acid biosynthetic process) | Biological process |
| **GO** | GO:0005737 (cytoplasm) | Cellular component |
| **CARD (Comprehensive Antibiotic Resistance Database)** | ARO:3000160 | Antibiotic resistance ontology entry |
| **ResFinder** | sul1 | Resistance gene identifier |
| **STRING** | P0C017 | Protein-protein interaction network (limited, as Sul1 has few known interactors) |
| **BioGRID** | N/A | No curated interactions for Sul1 |
| **Ensembl Bacteria** | Various | Genome context for *sul1* in bacterial genomes |

---

## Related Clinical & Scientific Guides

* [tpdA Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/tpda-gene-structure-function-pathway)
* [acm Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/acm-gene-structure-function-pathway)
* [P83002 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/p83002-gene-structure-function-pathway)

## References

[1] Venkatesan, M., Fruci, M., Verellen, L., Skarina, T., Mesa, N., Flick, R., Pham, C., Mahadevan, R., Stogios, P., & Savchenko, A. (2023). Molecular mechanism of plasmid-borne resistance to sulfonamide antibiotics. *Nature Communications*. URL: https://www.semanticscholar.org/paper/4242456cfe95dbba5920de743f9d3d71b493ec76

[2] Sköld, O. (2000). Sulfonamide resistance: mechanisms and trends. *Drug Resistance Updates*. URL: https://www.semanticscholar.org/paper/437e4b260a87a1ee4aec5252b24847afc9a5787a

[3] Razavi, M., Marathe, N., Gillings, M., Flach, C.-F., Kristiansson, E., & Larsson, D. G. J. (2017). Discovery of the fourth mobile sulfonamide resistance gene. *Microbiome*. URL: https://www.semanticscholar.org/paper/89aae850ce1aba48d4c42b203b4e1efc3e5fb011

[4] Sánchez-Osuna, M., Cortés, P., Barbé, J., & Erill, I. (2018). Origin of the Mobile Di-Hydro-Pteroate Synthase Gene Determining Sulfonamide Resistance in Clinical Isolates. *bioRxiv*. URL: https://www.semanticscholar.org/paper/ce2da7c08cbb42484f1f56f5f678dcd327b97076

[5] Antunes, P., Machado, J., Sousa, J., & Peixe, L. (N/A). Dissemination of Sulfonamide Resistance Genes (sul1, Sul2, and Sul3) in Portuguese Salmonella Enterica Strains and Relation with Integrons. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/11d4d486237385d70c5461cb800da2f382a47f68

[6] Shindoh, S., Kadoya, A., Kanechi, R., Watanabe, K., & Suzuki, S. (2023). Marine bacteria harbor the sulfonamide resistance gene sul4 without mobile genetic elements. *Frontiers in Microbiology*. URL: https://www.semanticscholar.org/paper/f9ece3f47688ef9c2d0b62fa1481f33f794aecc7

[7] Zhang, H., Yin, J., Jiang, H., Zeng, W., Cheng, Y., Yang, J., Lin, D., Bai, L., & Liang, H. (2025). Reduction of antibiotics and antibiotic resistance genes in simulated-sunlight-supported counter-diffusion bacteria-Algae biofilms: Interface properties and functional gene responses. *Water Research*. URL: https://www.semanticscholar.org/paper/932418fd0141965c7efd7d8fd711cf4269f205ef

[8] Nie, C., Chen, L., Zhao, B., Wu, Z., Zhang, M., Yan, Y., Li, B., & Xia, Y. (2024). Deciphering the adaptation mechanism of anammox consortia under sulfamethoxazole stress: A model coupling resistance accumulation and interspecies-cooperation. *Journal of Hazardous Materials*. URL: https://www.semanticscholar.org/paper/1dbe9e11b9404ba7ffa958ebd0122eb13d4a219a

[9] Daly, M., & Fanning, S. (2004). Integron analysis and genetic mapping of antimicrobial resistance genes in Salmonella enterica serotype Typhimurium. *Methods in Molecular Biology*. URL: https://www.semanticscholar.org/paper/c4c1921981d299827fc97a5916c3004782f2f992

[10] Yu, C.-C., Wei, X., Wang, Z., Liu, L., Liu, Z., Liu, J., Wu, L., Guo, H., & Jin, Z. (2020). Occurrence of two NDM-1-producing Raoultella ornithinolytica and Enterobacter cloacae in a single patient in China: probable a novel antimicrobial resistance plasmid transfer in vivo by conjugation. *Journal of Global Antimicrobial Resistance*. URL: https://www.semanticscholar.org/paper/6c52ced45a15a0594073e129391620208a30853f

[11] Chakraborty, A., & Roy, A. K. (2020). High Prevalence of Metal Resistant Genes in Salmonella enterica MDR Plasmids Correlates Severe Toxicities of Water with higher Typhoid AMR. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/49e1cd3842cbe914594e3e3bf8d9afd177fcf58c

[12] Hishinuma, A., Yoshida, A., Suzuki, H., Okuzumi, K., & Ishida, T. (2013). Complete sequencing of an IncFII NDM-1 plasmid in Klebsiella pneumoniae shows structural features shared with other multidrug resistance plasmids. *Journal of Antimicrobial Chemotherapy*. URL: https://www.semanticscholar.org/paper/d26e673d7202ef16d553c6bf773d427ce29278d8

[13] Sköld, O. (2001). Resistance to trimethoprim and sulfonamides. *Veterinary Research*. URL: https://www.semanticscholar.org/paper/d58128fecf1920c5678c4f86616c678932f44fbb

[14] Jiang, H., Dong, Y., Jiao, X., Tang, B., Feng, T., Li, P., & Fang, J. (2024). In vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli in the mammalian gut. *mSystems*. URL: https://www.semanticscholar.org/paper/514e52aa7bcab03cb72837112b58975dfc8586d1

[15] Ma, Q., Zhu, C., Yao, M., Yuan, G., & Sun, Y. (2021). Correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri and the sul genes. *Medicine*. URL: https://www.semanticscholar.org/paper/7a6716c2d92b320f17ec5a48f5bff8b373203166

[16] Mohd-Zain, Z., Kamsani, N. H., & Ahmad, N. (2013). Molecular insights of co-trimoxazole resistance genes in Haemophilus influenzae isolated in Malaysia. *Tropical Biomedicine*. URL: https://www.semanticscholar.org/paper/9e290172b1d47a0fa14661bcb6e01662563c8a16

[17] Mitra, S., Irshad, P., Anusree, M., Rekha, I., Shailaja, S., Suresh, J., Aishwarya, G., Shrestha, S., & Shome, B. (2021). Whole genome global insight of antibiotic resistance gene repertoire and virulome of high-risk multidrug-resistant Uropathogenic Escherichia coli. *Microbial Pathogenesis*. URL: https://www.semanticscholar.org/paper/8d57cf474b34e89f082ead2a226db616fbc05ef8

[18] Lai, Y., Zaw, M., Aung, T. S., Tin, W., & Lin, Z. (2019). Comparison of the Activities among Three SUL Genes Present in Uropathogenic Escherichia Coli. *Borneo Journal of Medical Sciences*. URL: https://www.semanticscholar.org/paper/ec7513836fc31f578b73cd25eee21cc1ae7e6764

[19] Hussein, I. A., Hamid, H. Q., Al-Shuwaikh, A. M., & Abdullah, R. M. (2022). Detection of sul1 resistance gene in Acinetobacter baumannii from different clinical cases. *Journal of the College of Basic Education*. URL: https://www.semanticscholar.org/paper/c7f1125a3db4fa680a809cdc8538c0e98ae8c89e

[20] Wang, H., Wang, J., Yu, P., Ge, P., Jiang, Y., Xu, R., Chen, R., & Liu, X. (2016). Identification of antibiotic resistance genes in the multidrug-resistant Acinetobacter baumannii strain, MDR-SHH02, using whole-genome sequencing. *International Journal of Molecular Medicine*. URL: https://www.semanticscholar.org/paper/a2868d62b243802e381b18960e33fc06a02f58a6

[21] Zhao, J., Xing, Y., Liu, W., Ni, W., Wei, C., Wang, R., Liu, Y., & Liu, Y. (2016). Surveillance of Dihydropteroate Synthase Genes in Stenotrophomonas maltophilia by LAMP: Implications for Infection Control and Initial Therapy. *Frontiers in Microbiology*. URL: https://www.semanticscholar.org/paper/7408b82a9d30c469798f22b12cde2e2ce6f3a5f5

[22] Bozhkova, M. (2016). Microbiological and Molecular Genetic Research on Epidemiology and Resistance to Antimicrobial Drugs in Clinical Isolates. Stenotrophomonas maltophilia. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/a43a1ea32792188be35c4b50d99d6e66e75ceb47

[23] Elfeil, W., Ezzat, M., Fathi, A., Alkilany, M.-A. A., & Abouelmaatti, R. R. (2020). Prevalence and Genotypic Analysis and Antibiotic Resistance of Salmonella Species Isolated from Imported and Freshly Slaughtered Chicken. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/8b20be2b1f54a3aefaab5e18a9e3a21a412b7807

[24] Borges-Rodríguez, Y., Stark, M. R., Kerckhofs, E., Mueller, J., Lauersen, K., Schubert, D., & Rader, S. D. (2026). Beyond CAT, BSD, and URA: SUL, A Novel Selectable Marker for Cyanidioschyzon merolae. *New Biotechnology*. URL: https://www.semanticscholar.org/paper/9a31b467bf76507d4431eb1d7125222a383f734a

[25] Thabit, Z., AlShaheeb, Z. A., Jaafar, M. R., Al-Qaysi, S. A. S., & Al-Shimmary, S. (2025). Multidrug resistance and virulence profile of the commensal Proteus mirabilis isolated from a native Iraqi frozen chicken carcass. *Journal of Genetic Engineering and Biotechnology*. URL: https://www.semanticscholar.org/paper/6b864f6a4d65abfe6b8d3d2009d8e850ce6c9d82

[26] Paris, L., Devers-Lamrani, M., Joly, M., Viala, D., de Antonio, M., Pereira, B., Rouard, N., Besse-Hoggan, P., Hébraud, M., Topp, E., Martin-Laurent, F., & Batisson, I. (2023). Effect of subtherapeutic and therapeutic sulfamethazine concentrations on transcribed genes and translated proteins involved in Microbacterium sp. C448 resistance and degradation. *FEMS Microbiology Ecology*. URL: https://www.semanticscholar.org/paper/c6dacfc9738a7b604b89f70c49879cfd0c5b1eb4

[27] Kadlec, K., & Schwarz, S. (2018). Antimicrobial Resistance in [Bordetella bronchiseptica](/knowledge/bacteria/pet-bacteria/bordetella-bronchiseptica). *Microbiology Spectrum*. URL: https://www.semanticscholar.org/paper/5f03a4d4768a56be5d0090f4c2bb129ff77ce0c7

[28] Farkas, A., Tarco, E., & Butiuc-Keul, A. (2019). Antibiotic resistance profiling of pathogenic Enterobacteriaceae from Cluj-Napoca, Romania. *GERMS*. URL: https://www.semanticscholar.org/paper/a9eb34b68cf89cb5c3d679fddf088b68b8c0b95d