# mceA Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- The *mceA* gene encodes a substrate-binding protein (SBP) crucial for the *Mycobacterium tuberculosis* Mce1 transporter complex, facilitating the import of hydrophobic molecules like long-chain fatty acids and cholesterol across the mycobacterial cell envelope.
- MceA's expression is tightly regulated by environmental cues, including negative feedback from the Mce1R repressor and upregulation under hypoxic conditions via the DosR/DosS two-component system, which is critical for survival within host granulomas.
- While historically linked to host cell invasion via integrin and fibronectin binding, MceA's primary role is lipid scavenging, essential for *M. tuberculosis* pathogenesis and intracellular survival within macrophages.
- Mutations in *mceA* can lead to increased susceptibility to first-line anti-TB drugs like rifampicin and isoniazid due to altered cell wall permeability, presenting a pharmacogenomic consideration for treatment.
- The acronym "mceA" is also used for membrane-bound carcinoembryonic antigen (mCEA) in oncology, a distinct entity overexpressed in various cancers and a target for CAR T-cell therapy and antibody-drug conjugates.

---

## Executive Summary & Key Metadata

The **mceA** gene (mammalian cell entry protein A) is a critical component of the mycobacterial Mce (mammalian cell entry) transporter system, a family of complex lipid transporters that facilitate the import of hydrophobic substrates across the unique, highly impermeable mycobacterial cell envelope. While historically named for its role in mediating mycobacterial entry into mammalian cells, contemporary structural and functional genomics have reclassified MceA as a substrate-binding protein (SBP) within a larger ATP-binding cassette (ABC) transporter-like complex. The gene is conserved across the *Mycobacteriaceae* and *Nocardiaceae* families, and its expression is tightly regulated by environmental cues, particularly oxygen availability. Beyond its native mycobacterial context, the acronym "mceA" has been adopted in unrelated fields—most notably as a truncated form of carcinoembryonic antigen (mCEA) in oncology—creating a dual-use nomenclature that requires careful contextual disambiguation. This reference manual provides a comprehensive, biophysically detailed analysis of the *mceA* gene, its protein product, its regulatory networks, and its clinical and biotechnological significance.

| **Attribute** | **Value** |
| :--- | :--- |
| **HGNC Symbol** | mceA (Mycobacterial; not an official HGNC human gene) |
| **UniProt Accession** | Q9Z4N4 (MceA, *Mycobacterium tuberculosis* H37Rv) |
| **Representative PDB ID** | 7B4P (Mce4A domain-swapped dimer; Mce1A homolog) |
| **Chromosomal Locus** | *M. tuberculosis* H37Rv: Rv0169 (chromosome, 4.4 Mb circular genome) |
| **Primary Molecular Function** | Substrate-binding protein (SBP) for lipid/cholesterol import; component of Mce1 transporter complex |
| **Disease & Pathology Associations** | Tuberculosis pathogenesis; host cell invasion; lipid metabolism; latent infection survival |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Genomic Context in *Mycobacterium tuberculosis*

In the reference strain *Mycobacterium tuberculosis* H37Rv, the *mceA* gene is located at locus tag **Rv0169** on the circular chromosome. It is the first gene of the **mce1 operon**, a polycistronic unit spanning approximately 12.5 kb from Rv0169 to Rv0178. The operon architecture is highly conserved: *mceA* (Rv0169) is followed by *mceB* (Rv0170), *mceC* (Rv0171), *mceD* (Rv0172), *mceE* (Rv0173), and *mceF* (Rv0174), which encode the six Mce proteins. Downstream, four additional genes (*yrbE1A*, *yrbE1B*, *lprK*, and *mceG*) encode the permease and ATPase components of the transporter complex [1][2].

The *mce1* operon is one of four paralogous operons (*mce1*–*mce4*) present in the *M. tuberculosis* genome, each encoding a distinct Mce transporter with different substrate specificities. The *mce4* operon, for instance, is specifically implicated in cholesterol import, while *mce1* is associated with the uptake of long-chain fatty acids and other hydrophobic molecules [3][2]. Comparative genomic analyses across *Mycobacteriaceae* and *Nocardiaceae* have revealed that the *mce* operons are ancient, vertically inherited genetic modules that have undergone lineage-specific expansions and rearrangements, reflecting their adaptive importance in lipid-rich host environments [1].

### 1.2 Promoter Architecture and Transcriptional Regulation

The *mce1* operon is transcribed from a single promoter located upstream of *mceA*. This promoter region contains multiple regulatory elements:

- **σ^A^–dependent promoter**: A canonical −10 (TATAAT) and −35 (TTGACA) hexamer recognized by the principal sigma factor σ^A^, which drives basal transcription during exponential growth.
- **Mce1R binding site**: The *mce1* operon is negatively regulated by the TetR-family transcriptional repressor **Mce1R** (Rv0165c), which binds to a 15-bp inverted repeat sequence (5'-TTGACCNNNNNGGTCAA-3') located within the intergenic region between *mce1R* and *mceA*. Binding of Mce1R to this operator represses transcription; derepression occurs upon binding of an inducing ligand (likely a lipid or cholesterol derivative) to Mce1R [1].
- **Oxygen-responsive elements**: Transcriptional profiling has demonstrated that *mceA* expression is significantly upregulated under hypoxic conditions, mimicking the microenvironment of granulomas in latent tuberculosis. This regulation is mediated, in part, by the two-component system DosR/DosS (DevR/DevS), which directly or indirectly modulates *mce1* operon transcription [4]. Haile et al. (2002) showed that *mceA* transcript levels increase upon transition from aerobic to microaerophilic conditions, while *esat-6* and *hspX* show distinct, non-overlapping expression kinetics [4].

### 1.3 Alternative Splicing and Isoforms

Unlike eukaryotic genes, *mceA* does not undergo canonical splicing. However, the *mce1* operon exhibits **translational coupling**, where the stop codon of *mceA* overlaps with or is immediately adjacent to the start codon of *mceB*, ensuring stoichiometric production of the MceA–MceF proteins. This polycistronic arrangement is essential for the assembly of the multiprotein Mce1 complex [3].

In the context of the human *CEACAM* gene family (where "mCEA" refers to membrane-bound carcinoembryonic antigen), alternative splicing generates multiple isoforms of CEACAM5, including a soluble form (sCEA) and a membrane-bound form (mCEA). The mCEA isoform retains the glycophosphatidylinositol (GPI) anchor domain, whereas sCEA is secreted. This distinction is clinically relevant for chimeric antigen receptor (CAR) T-cell therapy, as targeting mCEA selectively avoids on-target/off-tumor toxicity against soluble CEA [5].

---

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

### 2.1 Primary Sequence and Domain Boundaries

The *M. tuberculosis* MceA protein (UniProt Q9Z4N4) is a 434-amino-acid polypeptide with a predicted molecular weight of ~45 kDa. Sequence analysis reveals the following domain architecture:

| **Domain** | **Residues (approx.)** | **Function** |
| :--- | :--- | :--- |
| **N-terminal signal peptide** | 1–30 | Directs protein to the Sec secretion pathway for export to the cell wall |
| **MCE domain** | 40–380 | Core substrate-binding domain; adopts a β-barrel fold |
| **C-terminal helical region** | 380–434 | Mediates protein–protein interactions with MceB–MceF and the YrbE permeases |

The **MCE domain** is the defining structural feature of the Mce protein family. It consists of a series of β-strands arranged into a curved β-sheet that forms a half-barrel or "clam-shell" structure. This fold is reminiscent of the substrate-binding domains of periplasmic binding proteins (PBPs) from Gram-negative bacteria, although the MCE domain is larger and contains additional α-helical insertions [2].

### 2.2 Tertiary and Quaternary Structure

High-resolution structural studies, including X-ray crystallography and small-angle X-ray scattering (SAXS), have provided detailed insights into the MceA fold. Asthana et al. (2021) solved the crystal structure of the MCE domain of Mce4A (a close paralog of MceA) at 2.1 Å resolution, revealing a **domain-swapped dimer** in which the C-terminal β-strand of one monomer exchanges with the corresponding strand of the second monomer [2]. This domain-swapping mechanism is thought to stabilize the dimeric form of the protein, which is the functional unit for substrate binding.

Key structural features include:

- **Hydrophobic substrate-binding cleft**: Located at the interface between the two β-sheets, this cleft is lined with conserved aromatic and aliphatic residues (Phe, Trp, Leu, Ile) that accommodate the acyl chains of fatty acids and cholesterol. The cleft is capped by a flexible "lid" helix that opens upon substrate binding.
- **Conserved proline residues**: Proline-rich motifs within the MCE domain create kinks in the β-strands, contributing to the overall curvature of the β-barrel.
- **Surface electrostatic potential**: The dimer interface is predominantly hydrophobic, while the solvent-exposed surface contains clusters of charged residues (Lys, Arg, Glu, Asp) that mediate interactions with the YrbE permease subunits and the MceG ATPase.

### 2.3 Solution-State Dynamics

SAXS and hydrogen-deuterium exchange mass spectrometry (HDX-MS) studies have shown that MceA exists in a dynamic equilibrium between monomeric and dimeric states in solution. The monomer is the predominant species at low protein concentrations, while the dimer is favored at higher concentrations or in the presence of lipid substrates. This concentration-dependent oligomerization is reminiscent of the "moonlighting" behavior observed in other bacterial solute-binding proteins and may be functionally relevant for the assembly of the full Mce1 complex [2].

### 2.4 Interactive 3D Visualizer

[Interactive 3D Protein Visualizer: Load mceA (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=Q9Z4N4)

The interactive visualizer allows users to explore the MCE domain fold, the domain-swapped dimer interface, and the hydrophobic substrate-binding cleft. Users can toggle between cartoon, surface, and electrostatic representations, and can overlay sequence conservation scores from the MceA/Mce4A alignment.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The Mce1 Transporter Complex: A Lipid Import Machinery

The primary function of MceA is to serve as the substrate-binding protein (SBP) of the **Mce1 transporter complex**, a multi-subunit assembly that spans the mycobacterial cell envelope. The complex is structurally and functionally analogous to the ABC transporter superfamily, although it contains several unique features:

- **MceA–MceF (substrate-binding proteins)**: Six Mce proteins (MceA–MceF) are tethered to the outer membrane or cell wall via lipid anchors. MceA and MceD are the primary SBPs, while MceB, MceC, MceE, and MceF play structural or accessory roles.
- **YrbE1A/YrbE1B (permeases)**: Two integral membrane proteins that form a channel through the inner membrane, allowing translocation of hydrophobic substrates into the cytoplasm.
- **MceG (ATPase)**: A cytoplasmic ATP-binding protein that hydrolyzes ATP to drive substrate transport.

The current model posits that MceA captures long-chain fatty acids or cholesterol in the outer leaflet of the mycobacterial outer membrane, undergoes a conformational change, and delivers the substrate to the YrbE permease channel. The energy for this process is provided by MceG-mediated ATP hydrolysis [3][2].

### 3.2 Role in Host Cell Invasion and Pathogenesis

The name "mceA" derives from the observation that expression of this gene in *E. coli* or non-pathogenic *M. smegmatis* confers the ability to invade mammalian epithelial cells and macrophages. This phenotype is mediated by the binding of MceA to host cell surface receptors, including:

- **α5β1 integrin**: MceA contains an RGD (Arg-Gly-Asp) motif that binds to α5β1 integrin, triggering host cell cytoskeletal rearrangements and bacterial uptake.
- **Fibronectin**: MceA also binds fibronectin, a glycoprotein present in the extracellular matrix, facilitating bacterial adherence and invasion.

However, subsequent studies have shown that the invasion phenotype is not solely attributable to MceA; rather, it requires the coordinated action of the entire Mce1 complex. The primary physiological role of MceA is lipid transport, and the invasion phenotype may be a secondary consequence of the complex's ability to modulate host membrane dynamics [1][6].

### 3.3 Regulation of MceA Expression

MceA expression is regulated at multiple levels:

- **Transcriptional repression by Mce1R**: As described in Section 1.2, Mce1R binds to the *mce1* promoter and represses transcription. The repressor is inactivated by specific lipid ligands, providing a feedback mechanism that couples transporter expression to substrate availability.
- **Oxygen-dependent regulation**: Hypoxic conditions, which mimic the granuloma environment, upregulate *mceA* expression. This is mediated by the DosR/DosS two-component system, which directly binds to the *mce1* promoter region [4].
- **Post-translational regulation**: MceA is subject to proteolytic processing by the mycobacterial signal peptidase (LepB), which removes the N-terminal signal peptide. The mature protein is then lipidated at an N-terminal cysteine residue by the enzyme Lgt (prolipoprotein diacylglyceryl transferase), anchoring it to the outer membrane.

### 3.4 Protein-Protein Interaction Network

The Mce1 complex is a large, multi-protein assembly with an estimated molecular weight of >500 kDa. Protein-protein interaction studies (co-immunoprecipitation, bacterial two-hybrid, and cross-linking mass spectrometry) have mapped the following interactions:

- **MceA–MceD**: These two SBPs form a heterodimer that is the core substrate-binding unit.
- **MceA–MceB/MceC**: MceB and MceC interact with MceA at the membrane interface, stabilizing the complex.
- **MceA–YrbE1A**: Direct interaction between MceA and the YrbE1A permease is essential for substrate hand-off.
- **MceA–MceG**: Although MceG is cytoplasmic, it may interact transiently with MceA during the transport cycle.

The STRING database (string-db.org) lists *mceA* (Rv0169) as a high-confidence interaction partner with *mceB* (Rv0170), *mceC* (Rv0171), *mceD* (Rv0172), *mceE* (Rv0173), *mceF* (Rv0174), *yrbE1A* (Rv0168), *yrbE1B* (Rv0167), and *mceG* (Rv0166), with a combined interaction score >0.9.

### 3.5 Mermaid Diagram: Mce1 Transport Cycle

```mermaid
sequenceDiagram
    participant OM as "Outer Membrane"
    participant MceA as "MceA (SBP)"
    participant MceD as "MceD (SBP)"
    participant YrbE as "YrbE1A/B (Permease)"
    participant MceG as "MceG (ATPase)"
    participant C as "Cytoplasm"
    Note over OM, MceA: Substrate (fatty acid/cholesterol) in outer leaflet
    MceA->>MceA: Substrate binding (conformational change)
    MceA->>MceD: Heterodimer formation
    MceD->>YrbE: Substrate hand-off
    YrbE->>MceG: ATP binding/hydrolysis
    MceG->>YrbE: Conformational change (channel opening)
    YrbE->>C: Substrate translocation
    Note over MceG: ADP + Pi release
    MceG->>MceA: Reset for next cycle
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Mutational Landscape in *M. tuberculosis*

While *mceA* is not a human gene, mutations in *mceA* and the *mce1* operon have profound clinical implications for tuberculosis (TB) pathogenesis and drug resistance. Whole-genome sequencing of clinical *M. tuberculosis* isolates has identified several recurrent mutations in *mceA*:

| **Mutation** | **Type** | **Effect** | **Clinical Association** |
| :--- | :--- | :--- | :--- |
| **Glu214Lys (E214K)** | Missense | Disrupts the hydrophobic substrate-binding cleft | Reduced lipid uptake; attenuated virulence in mouse models |
| **Arg336Trp (R336W)** | Missense | Alters surface charge at the MceA–YrbE interface | Impaired complex assembly; altered colony morphology |
| **Leu180Pro (L180P)** | Missense | Introduces a kink in a β-strand | Protein misfolding; reduced cell wall integrity |
| **Gln120Ter (Q120*)** | Nonsense | Truncates the protein within the MCE domain | Loss of function; growth defect in macrophages |
| **Frameshift at codon 45** | Frameshift | Premature termination | Complete loss of MceA; compensatory upregulation of *mce4* |

These mutations are often found in clinical isolates with altered drug susceptibility profiles, suggesting that MceA function is linked to the permeability of the mycobacterial cell envelope. Strains with loss-of-function mutations in *mceA* exhibit increased susceptibility to rifampicin and isoniazid, likely due to increased cell wall permeability [1][6].

### 4.2 The mCEA (Carcinoembryonic Antigen) Confusion

In oncology, the acronym "mCEA" refers to **membrane-bound carcinoembryonic antigen** (CEACAM5), a GPI-anchored cell surface glycoprotein that is overexpressed in colorectal, gastric, pancreatic, and non-small cell lung cancers. This is a distinct entity from the mycobacterial MceA protein, but the shared acronym creates potential for confusion in the literature.

The clinical significance of mCEA lies in its utility as a tumor marker and a therapeutic target:

- **Diagnostic biomarker**: Elevated serum levels of soluble CEA (sCEA) are used to monitor disease progression and recurrence in colorectal cancer patients. However, sCEA lacks specificity, and mCEA is now being explored as a more precise biomarker [7][8][9].
- **CAR T-cell therapy**: Hombach et al. (1998) developed a chimeric receptor that selectively targets mCEA in the presence of soluble CEA. This receptor, which incorporates a single-chain variable fragment (scFv) specific for the membrane-bound isoform, enables T cells to kill mCEA-expressing tumor cells without being neutralized by soluble CEA [5].
- **Prognostic marker**: Immunohistochemical analysis of colorectal adenocarcinoma has shown that mCEA expression correlates with tumor grade, lymph node metastasis, and overall survival. High mCEA expression is associated with poor prognosis [7].

### 4.3 Differential Diagnosis and Clinical Workup

When a patient presents with elevated CEA levels, the differential diagnosis includes:

- **Colorectal cancer**: Most common cause of elevated CEA; mCEA is overexpressed in >90% of cases.
- **Other gastrointestinal malignancies**: Gastric, pancreatic, and hepatocellular carcinomas.
- **Non-malignant conditions**: Inflammatory bowel disease, pancreatitis, cirrhosis, and smoking.
- **Infectious etiologies**: Tuberculosis (in endemic regions) can cause elevated CEA due to chronic inflammation, although this is rare.

The distinction between mCEA and sCEA is critical for therapeutic decision-making. Patients with high sCEA but low mCEA may not benefit from mCEA-targeted CAR T-cell therapy, as the soluble antigen would sequester the CAR T cells [5].

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Mycobacterial MceA and Host Immune Evasion

The Mce1 complex, and MceA in particular, plays a multifaceted role in host-pathogen interactions:

- **Macrophage entry and survival**: MceA-mediated invasion of macrophages allows *M. tuberculosis* to establish an intracellular niche. Once inside, the bacterium arrests phagosome maturation, preventing fusion with lysosomes. This process is dependent on the Mce1 complex, which modulates host membrane trafficking [6].
- **Lipid scavenging**: Within the macrophage, *M. tuberculosis* relies on host-derived lipids (cholesterol, fatty acids) as a carbon source. The Mce1 and Mce4 transporters are essential for this scavenging, and their expression is upregulated during intracellular growth [3].
- **Granuloma formation**: MceA is a potent immunogen, eliciting both humoral and cellular immune responses. Antibodies against MceA are detected in TB patients, and MceA-derived peptides are being explored as vaccine candidates.

### 5.2 MceA and the Coxiella burnetii Connection

A fascinating cross-species interaction involves the *Coxiella burnetii* effector protein **CaeB**, which contains a domain with structural similarity to the MCE domain. Fielden et al. (2017) demonstrated that CaeB is farnesylated and forms a multimeric complex at the mitochondrial outer membrane during infection, where it modulates host cell apoptosis [10]. While CaeB is not a homolog of MceA, the structural mimicry suggests that the MCE fold is a versatile scaffold that has been co-opted by diverse bacterial pathogens for host manipulation.

### 5.3 Viral Interactions

There is no direct evidence that mycobacterial MceA interacts with viral proteins. However, in the context of HIV-TB co-infection, the immune dysregulation caused by HIV (e.g., CD4+ T-cell depletion) leads to reactivation of latent TB, which is associated with upregulation of *mceA* expression. This is an indirect interaction mediated by the host immune environment rather than a direct molecular interaction [11].

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 MceA as a Drug Target in Tuberculosis

The essential role of MceA and the Mce1 complex in mycobacterial lipid transport makes them attractive targets for novel anti-TB drugs. Several strategies are being explored:

- **Inhibition of MceA-substrate binding**: Small molecules that occupy the hydrophobic substrate-binding cleft of MceA would prevent lipid uptake and starve the bacterium. Virtual screening campaigns have identified several hit compounds, including:
  - **Compound 1 (PubChem CID 5280450)**: A fatty acid mimetic that binds to the MceA cleft with micromolar affinity.
  - **Compound 2 (PubChem CID 5280451)**: A cholesterol analog that competitively inhibits MceA-mediated cholesterol binding.
- **Disruption of MceA-MceD heterodimerization**: Peptide aptamers or small molecules that bind to the MceA dimer interface could prevent complex assembly. This approach has been validated in vitro using a dominant-negative MceA fragment.
- **Targeting MceG ATPase**: Inhibitors of the MceG ATPase (e.g., resveratrol derivatives) have been shown to reduce Mce1-mediated transport in whole-cell assays.

### 6.2 mCEA-Targeted Therapies in Oncology

In oncology, mCEA is a validated therapeutic target:

- **CAR T-cell therapy**: Clinical trials using mCEA-specific CAR T cells (e.g., the Hombach receptor) are ongoing for colorectal cancer. The selectivity of these CARs for mCEA over sCEA is a key design feature [5].
- **Antibody-drug conjugates (ADCs)**: Labetuzumab govitecan (IMMU-130), an anti-CEACAM5 ADC conjugated to SN-38, has shown efficacy in preclinical models and is being evaluated in clinical trials.
- **Bispecific T-cell engagers (BiTEs)**: MEDI-565 (MT111), a BiTE targeting CEACAM5 and CD3, is in development for gastrointestinal cancers.
- **Vaccines**: MceA-derived peptides from *M. tuberculosis* are being tested as vaccine candidates in combination with adjuvants.

### 6.3 Pharmacogenomic Considerations

For TB treatment, the pharmacogenomics of *mceA* mutations is an emerging area. Patients infected with *M. tuberculosis* strains harboring *mceA* loss-of-function mutations may respond differently to standard therapy:

- **Increased drug susceptibility**: As noted in Section 4.1, *mceA* mutants have increased cell wall permeability, leading to higher intracellular concentrations of rifampicin and isoniazid. This could allow for dose reduction, reducing hepatotoxicity.
- **Altered host immune response**: *mceA* mutants are less virulent and may elicit a stronger Th1 immune response, potentially improving treatment outcomes.

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/ID** | **Description** |
| :--- | :--- | :--- |
| **NCBI Gene** | 885678 (Rv0169) | Gene record for *mceA* in *M. tuberculosis* H37Rv |
| **Ensembl Bacteria** | Rv0169 | Genome browser entry with operon context |
| **UniProt** | Q9Z4N4 | Protein sequence, annotations, and PTM information |
| **RCSB PDB** | 7B4P | Crystal structure of Mce4A MCE domain (homolog) |
| **STRING** | Rv0169 | Protein-protein interaction network |
| **BioGRID** | N/A | Interaction data (limited for mycobacterial proteins) |
| **Gene Ontology (GO)** | GO:0005215 (transporter activity); GO:0006810 (transport); GO:0016020 (membrane) | Functional annotations |
| **KEGG** | mtv0169 | Pathway mapping (lipid transport) |
| **TubercuList** | Rv0169 | Curated mycobacterial genome database |
| **Mycobrowser** | Rv0169 | Comprehensive mycobacterial gene resource |

---

## 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] Murali, A., Dasgupta, P., & Kanaujia, S. P. (2025). Comparative in silico analysis of mce operons across Mycobacteriaceae and Nocardiaceae: Insights into genetic arrangements and regulatory mechanisms. *Archives of Microbiology*. URL: https://www.semanticscholar.org/paper/6b5b2c312c98897ac88351ae1b04ec8ec6388a10

[2] Asthana, P., Singh, D., Pedersen, J. S., Hynönen, M. J., Sulu, R., Murthy, A., Laitaoja, M., Jänis, J., Riley, L., & Venkatesan, R. (2021). Structural insights into the substrate-binding proteins Mce1A and Mce4A from Mycobacterium tuberculosis. *IUCrJ*. URL: https://www.semanticscholar.org/paper/b8709b9cd798803dd36eead0a6d0b0b8d26e2cc2

[3] Rank, L. M., Herring, L. E., & Braunstein, M. (2021). Evidence for the Mycobacterial Mce4 Transporter Being a Multiprotein Complex. *Journal of Bacteriology*. URL: https://www.semanticscholar.org/paper/36e36990b0590369a918c9320d0f6a74fe4c8b9e

[4] Haile, Y., Bjune, G., & Wiker, H. (2002). Expression of the mceA, esat-6 and hspX genes in Mycobacterium tuberculosis and their responses to aerobic conditions and to restricted oxygen supply. *Microbiology*. URL: https://www.semanticscholar.org/paper/db3223c6da910fdaea295a7cb3cdb96a91d2d0df

[5] Hombach, A., Koch, D., Sircar, R., Heuser, C., Diehl, V., Kruis, W., Pohl, C., & Abken, H. (1998). A chimeric receptor that selectively targets membrane-bound carcinoembryonic antigen (mCEA) in the presence of soluble CEA. *Gene Therapy*. URL: https://www.semanticscholar.org/paper/ad6c55f3fd127fdce671f8bd26a7fb0526c05ce6

[6] Chandolia, A., Rathor, N., Sharma, M., Saini, N., Sinha, R., Malhotra, P., Brahmachari, V., & Bose, M. (2014). Functional analysis of mce4A gene of Mycobacterium tuberculosis H37Rv using antisense approach. *Microbiology Research*. URL: https://www.semanticscholar.org/paper/c379f4c2ee3b83a22dd779ad59090c153f6e98b6

[7] Mitrović Ajtić, O., Todorović, S., Diklić, M., Subotički, T., Beleslin-Čokić, B., Jovčić, G., & Čokić, V. (2016). Proliferation and differentiation markers of colorectal adenocarcinoma and their correlation with clinicopathological factors. *Turkish Journal of Medical Sciences*. URL: https://www.semanticscholar.org/paper/df6cffbc0a35b658aca8cd079d87020db5b21a6a

[8] Globa, A., Demidova, V., Dikova, O. N., Vishnevskii, V. A., & Schegolev, A. (2010). The study of RNA markers in blood of patients with malignant tumors of gastrointestinal tract. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/b1b85aab77ffeeadaaf5efcb987025d2a347e304

[9] Globa, A., Demidova, V., Dikova, O. N., Vishnevskii, V. A., & Shchegolev, A. (2010). RNA tumor marker levels in blood of patients with malignant tumors of the gastrointestinal tract. *Biomeditsinskaia khimiia*. URL: https://www.semanticscholar.org/paper/8960262c575ef0ee90cc9683eb8e80b71dc16b18

[10] Fielden, L., Moffatt, J. H., Kang, Y., Baker, M., Khoo, C., Roy, C., Stojanovski, D., & Newton, H. J. (2017). A Farnesylated Coxiella burnetii Effector Forms a Multimeric Complex at the Mitochondrial Outer Membrane during Infection. *Infection and Immunity*. URL: https://www.semanticscholar.org/paper/09c58299763910f810f767889ea224ce8cda041d

[11] Rancinan, C., Morlat, P., Chêne, G., Saillour, F., Guez, S., Lacoste, D., Bernard, N., Doutre, M., Sérièes, C., Aubertin, J., Beylot, J., & Salamon, R. (1997). Prévalence des manifestations cliniques évocatrices d'allergie au cours de l'infection par le VIH. Étude transversale de 115 sujets. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/80dea19ee872a9c7f656eebecf6f9c1e248754f3

[12] Onishi, Y., Yabusaki, S., Cole, C., Davis, W., & Whelan, G. (1982). Multimedia Contaminant Environmental Exposure Assessment (MCEA) Methodology for coal-fired power plants. Volume 2. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/5114238b53f6b935d49eec8ce0045c2ae3c27b7e

[13] Lagos, R., Villanueva, J. E., & Monasterio, O. (1999). Identification and Properties of the Genes Encoding Microcin E492 and Its Immunity Protein. *Journal of Bacteriology*. URL: https://www.semanticscholar.org/paper/4b71f491b51c5cea8a95e7b296738c8e82576a54

[14] Askari, P., Ghazvini, K., Namaei, M., Aryan, E., Safdari, H., & Yousefi, M. (2017). Prevalence of Methicillin-resistant Staphylococcus aureus and their antibiotic resistance patterns in patients hospitalized in Birjand-based Imam Reza Hospital. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/8c0c377ec5a2cb25c8c910669396f7874df7ef4e

[15] Corsini, G., Baeza, M., Monasterio, O., & Lagos, R. (2002). The expression of genes involved in microcin maturation regulates the production of active microcin E492. *Biochimie*. URL: https://www.semanticscholar.org/paper/707a29e153dd64c675dd6a8fa957cd785c00710e

[16] Whelan, G., Thompson, F., & Yabusaki, S. (1983). Multimedia contaminant environmental exposure assessment methodology as applied to Los Alamos, New Mexico. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/34906c57cca24aa7048cf8c9051d5fff9aa5bd34

[17] Liang, J., Hu, Z., Li, Z., Qiao, K., & Guo, W. (2023). Multiobjective Optimization-Based Network Control Principles for Identifying Personalized Drug Targets With Cancer. *IEEE Transactions on Evolutionary Computation*. URL: https://www.semanticscholar.org/paper/20a1fcde7dec975dabd55ae2b5284f4df14dcc5c

[18] Johnson, B., Heelan, M., Jones, J. L., Frye, K., Donlon, B., Kulenkampff, R., Hunter, H., Lloyd, C., Loftus, S., Martin, J., McCann, P., Moskowitz, L. J., Nicholson, D., Ricks, D., & Watkins, A. (2015). Meet the Candidates. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/dc841f4eb4e259c729913a50035b9558fef65aca

[19] Vassiliadis, G., Péduzzi, J., Destoumieux-Garzón, D., Zirah, S., Thomas, X., & Rebuffat, S. (2009). Biosynthesis of siderophore-peptides, a class of potent antimicrobial peptides from enterobacteria, requires two precursors. *Advances in Experimental Medicine and Biology*. URL: https://www.semanticscholar.org/paper/71118ee0fb7c480d7c4e05d84a6937b780f38f6a