Overcoming nutritional immunity by engineering iron-scavenging bacteria for cancer therapy

Certain bacteria demonstrate the ability to target and colonize the tumor microenvironment, a characteristic that positions them as innovative carriers for delivering various therapeutic agents in cancer therapy. Nevertheless, our understanding of how bacteria adapt their physiological condition to the tumor microenvironment remains elusive. In this work, we employed liquid chromatography-tandem mass spectrometry to examine the proteome of E. coli colonized in murine tumors. Compared to E. coli cultivated in the rich medium, we found that E. coli colonized in tumors notably upregulated the processes related to ferric ions, including enterobactin biosynthesis and iron homeostasis. This finding indicated that the tumor is an iron-deficient environment to E. coli. We also found that the colonization of E. coli in the tumor led to an increased expression of lipocalin 2 (LCN2), a host protein that can sequester enterobactin. We therefore engineered E. coli to evade the nutritional immunity p..., , , # Overcoming nutritional immunity by engineering iron-scavenging bacteria for cancer therapy

We have submitted our raw data sets, including **\"In vivo.raw\"** (Mass spectrometry-based label-free quantification proteomics analysis of intratumoral *E. coli*), **\"In LB.raw\"** (Mass spectrometry-based label-free quantification proteomics analysis of *E. coli* in LB medium), and \"**Proteomics data.xlsx**”.

## **Fie Descriptions**

Proteomics data.xlsx_data:

l   **Significant**: The observed protein abundance difference between samples is statistically significant.

l   **-LOG(P-value)**: The negative logarithm of the p-value, representing the significance of the protein abundance difference, where higher values indicate higher significance.

l   **Difference**: The fold change or difference in protein abundance between the compared conditions or samples.

l   **T: Protein IDs**: The unique identifiers for the proteins detected in the experiment.

l   **T: Majority protein IDs**: The identi...