Engineered Gut Peptide SPRR2A Kills Both Bacteria and Breast Cancer Cells Through Membrane Disruption | Research

The takeaway

Recombinant Trx-SPRR2A with five correctly-formed disulfide bonds showed dual antibacterial (selective Gram-positive) and anticancer (MCF-7 at acidic pH) activity through membrane disruption and apoptosis.

Kills bacteria AND cancer
SPRR2A disrupts membranes of both Gram-positive bacteria and breast cancer cells (at acidic pH), making it a rare dual-function therapeutic

What the researchers found

Trx-SPRR2A: 7.18 mg/L yield, 94.5% purity, 5 correct disulfide bonds. Antibacterial: selective Gram-positive. Anticancer: MCF-7 selective at acidic pH. Mechanism: membrane disruption (both) + apoptosis (cancer).

Why it matters

A single peptide that fights both infection and cancer through the same mechanism (membrane disruption) is exceptionally versatile for therapeutic development.

How the study worked

Recombinant expression in E. coli Rosetta-gami pLysS, disulfide bond verification, stability testing (thermal, serum), antimicrobial spectrum, cancer cell selective cytotoxicity at different pH, and mechanism studies.

What this study cannot tell us

In vitro only. Gram-positive selectivity limits antibacterial spectrum. Cancer activity tested on MCF-7 only. Acidic pH requirement limits applications.

How to read the evidence

Proof-of-concept with successful recombinant production and dual activity validation. Novel but in vitro only.

When this study was published

Published in 2025.

The bigger picture

Dual-function antimicrobial/anticancer peptides are rare. SPRR2A's pH-selective cancer activity aligns perfectly with the acidic tumor microenvironment.

Questions still open

Could SPRR2A be delivered specifically to tumor sites for dual anti-infection + anticancer activity?
Does pH-selective cytotoxicity extend to other cancer types?
Would combination with Gram-negative-active AMPs broaden antibacterial spectrum?

Common questions

Can one peptide fight both infections and cancer?

SPRR2A does both: it kills Gram-positive bacteria by disrupting their membranes, and it kills breast cancer cells the same way — but only under the acidic conditions found in tumors, making it cancer-selective.

Why is pH selectivity important?

Tumors are more acidic than normal tissue. A peptide that only kills cells at acidic pH will attack cancer cells while leaving healthy cells unharmed — natural tumor targeting.

Read the original research

Engineered Bacterial Biosynthesis of a Cysteine-Rich SPRR2A Fusion Protein with Dual Antibacterial and Anticancer Efficacy.

ACS synthetic biology, 15(2), 854-866

View on PubMed ↗Publisher’s paper ↗

Citation

He, Pinlong; Liu, Hongrui; Yuan, Junyi; Gao, Hui; Li, Bin-Chun; Stauber, Roland H; Li, Bozhao; Ding, Guo-Bin. (2026). Engineered Bacterial Biosynthesis of a Cysteine-Rich SPRR2A Fusion Protein with Dual Antibacterial and Anticancer Efficacy.. ACS synthetic biology, 15(2), 854-866. https://doi.org/10.1021/acssynbio.6c00021