Indolicidin
A tryptophan-rich antimicrobial peptide from cattle, active against microbes in the laboratory but too toxic to red cells to use as it is
Indolicidin is a 13-amino-acid peptide found in the granules of cow white blood cells, part of their defence against microbes. Five of its residues are tryptophan, the highest share known in any natural protein sequence. In the laboratory it is active against many bacteria and fungi, partly by breaking microbial membranes and partly by blocking DNA synthesis inside the cell. It also damages human red blood cells at similar strengths, so it has worked in animals only when packaged in fat particles. It has never been given to people; its redesigned analogue omiganan has its own entry.
No established human dose Details ↓
Recommended Dosing
No established human dose
No study has given indolicidin to a person. The human-relevant work is laboratory testing against bacteria, fungi and HIV and a handful of animal infection models, in which the free peptide was too toxic to red blood cells to use until it was packaged in fat particles.
What is it?
Indolicidin was purified in 1992 from the granules of cow neutrophils, where it is stored ready to kill microbes the cell engulfs. Its 13 residues include five tryptophans and three prolines, an unusual make-up that gives it no ordinary helix or sheet shape, and the end of the chain carries an amide cap. The gene was cloned the same year: the peptide is cut from a larger precursor, and the family it belongs to, the cathelicidins, includes the single human member LL-37.
Its appeal is a broad reach. In laboratory tests it kills Gram-positive and Gram-negative bacteria and fungi at low concentrations, and an early study reported that it can inactivate HIV in the dish, consistent with it acting on membranes. Because resistance to ordinary antibiotics keeps spreading, small natural peptides like this one are studied as a different line of attack, and indolicidin is one of the most examined.
How it kills has been picked apart over three decades. It binds the lipopolysaccharide of Gram-negative outer membranes and crosses into the cell, then forms channels in the inner membrane that let the contents leak; but it does not simply burst bacteria. It also enters the cell and binds DNA, and it blocks DNA synthesis, which makes bacteria grow into long filaments. Studies of its structure in membranes and bound to DNA support this double action, membrane and target inside.
The obstacle to using it is that the same features that break microbial membranes break human ones. At the concentrations that kill microbes it also ruptures red blood cells, and the tryptophans that drive its activity also drive this toxicity. Wrapping it in fat particles (liposomes) sharply lowered that toxicity in mice: free peptide killed at 0.4 mg/kg while the liposomal form was tolerated at 40 mg/kg, and only the packaged form cured mice with a systemic fungal infection, the first report of an animal cure with a neutrophil peptide.
Most work since has been in the test tube or in insect and rodent infection models: against multidrug-resistant gut bacteria in wax-moth larvae, against resistant Acinetobacter with the antibiotic tigecycline, and, in mice, damping the inflammation of sepsis while lowering microbe counts. None of this has reached a human trial. The route that did reach people was redesign: omiganan, a modified version built to keep the activity and lose the toxicity, was taken into phase 3 trials and is covered in its own entry. Indolicidin itself is a research compound, approved nowhere and sold as nothing.
Mechanism of Action
Indolicidin attacks microbes two ways at once, and the same chemistry harms human cells, which is why it stays a research peptide.
Membrane channels
It crosses the outer membrane and opens channels in the inner membrane of bacteria, letting the contents leak (PMID 8702613).
Blocks DNA synthesis
Inside the cell it binds DNA and stops DNA synthesis, making bacteria grow into filaments (PMID 9495018).
Harms red cells too
Its tryptophans, which drive its activity, also rupture human red blood cells at similar strengths (PMID 8849687).
Published Research
These studies were read from their PubMed abstracts on October 29, 2026. All are laboratory or animal work: there is no human study of indolicidin. Papers on its redesigned analogue omiganan belong on that entry; its own analogue and delivery papers are listed under References.
Discovery: the tryptophan-rich peptide
The peptide was purified from cow neutrophil granules and nearly sterilised suspensions of Staphylococcus aureus and Escherichia coli at 10 micrograms/mL. It is 13 residues long with five tryptophans, the highest tryptophan share of any known sequence, and an amidated end; the authors named it indolicidin.
Cloning the gene
The peptide is made in bone marrow cells as a 144-residue precursor with a signal piece and a long pro-region, with the mature peptide at the far end. An extra glycine in the deduced sequence, absent from the purified peptide, marks where the amide cap is added.
Mode of action: channels in the membrane
Indolicidin bound bacterial lipopolysaccharide and made the outer membrane of E. coli leaky, then formed discrete channels in the inner membrane that opened under a voltage. Capping its end as a methyl ester raised its activity, placing the killing at the cytoplasmic membrane.
It also blocks DNA synthesis
Although it permeabilised bacterial membranes, indolicidin did not lyse the cells. It made E. coli grow into filaments and selectively inhibited DNA synthesis while sparing RNA and protein synthesis, so a second action inside the cell adds to the membrane effect.
Multiple shapes, binding membranes and DNA
Structure studies found the peptide takes several shapes, a globular form in water and a wedge in membranes, and showed by several methods that it binds DNA with a sequence preference, supporting a model in which it works on membranes at some concentrations and on DNA at others.
What the tryptophans and prolines do
Swapping proline for alanine or tryptophan for phenylalanine kept antibacterial activity, but the phenylalanine version lost the ability to rupture red blood cells, showing that the tryptophans are what make the peptide damage human membranes.
Active against HIV in the dish
Indolicidin inactivated HIV-1 in culture at 333 micrograms/mL, with killing within an hour and a temperature dependence pointing to a membrane effect; but it also lysed cultured lymphoid cells at similar strengths, while a shortened analogue was both less active and less toxic.
Fungicidal, by hitting the membrane
The peptide killed several fungi and acted on the plasma membrane of Trichosporon beigelii quickly and without needing the cell's energy, changing the shape of model lipid vesicles, which points to direct membrane disruption.
Packaged in liposomes, it cured infected mice
Wrapping indolicidin in fat particles lowered its toxicity to cultured cells and, in mice, raised the dose tolerated without deaths from 0.4 to 40 mg/kg. Only the packaged form cured mice with a systemic Aspergillus infection, the first report of an animal cure with a neutrophil-derived peptide.
With an antibiotic in rat peritonitis
In two rat models of mixed abdominal infection, indolicidin alone, piperacillin/tazobactam alone and the two together all cut bacterial growth and deaths against saline. Indolicidin lowered blood endotoxin and cytokine levels, and the combination worked best.
Multidrug-resistant E. coli in wax-moth larvae
Against resistant enteroaggregative E. coli, indolicidin had a minimum inhibitory concentration of 32 micromolar, was stable to heat and salts, spared human cell lines and gut-friendly lactobacilli at active strengths, and improved survival of infected Galleria mellonella larvae.
Pairing with tigecycline against resistant Acinetobacter
Against ten multidrug-resistant Acinetobacter baumannii isolates from wounds, combining indolicidin with tigecycline was strongly synergistic, dropping the amount of each drug needed and cutting biofilm formation by about 78%.
Damping inflammation in mouse sepsis
In mouse models of bacterial and fungal sepsis, indolicidin improved survival and lowered microbe counts in the kidneys, and in macrophages it bound lipopolysaccharide and reduced TLR4 signalling, acting as both an antimicrobial and an anti-inflammatory peptide.
Indolicidin revisited
The review summarises the peptide's activity against bacteria, fungi, viruses and tumour cells and the analogues and formulations built on it, and states plainly that it is not yet approved for commercial use.
Delivery systems for indolicidin
This review centres on the problem that limits the peptide, rapid breakdown and toxicity to host cells, and surveys the nanocarriers, hydrogels and liposomes being tried to deliver it while managing those drawbacks.
No Established Human Dose
No study has given indolicidin to a person. The human-relevant work is laboratory testing against bacteria, fungi and HIV and a handful of animal infection models, in which the free peptide was too toxic to red blood cells to use until it was packaged in fat particles. The compound that did reach people is the redesigned analogue omiganan, not indolicidin, so there is no human dose and none can be drawn from the animal work.
What this rests on: PMID 1537821, PMID 9469478, PMID 7632702.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Indolicidin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Indolicidin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Indolicidin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Indolicidin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Indolicidin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Indolicidin lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: Ruptures human red blood cells at the concentrations that kill microbes (PMID 8849687); Toxic to cultured lymphoid and other human cells near its active range (PMID 9469478); In mice, the free peptide was lethal above 0.4 mg/kg; packaging it in liposomes raised the tolerated dose 100-fold (PMID 7632702). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Indolicidin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“No human data exist”).
Interactions
Unknown: a PubMed search for human interaction studies of Indolicidin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Indolicidin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Indolicidin's expected mass, 1,906.3 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved: Drugs@FDA, the EMA medicines list and ClinicalTrials.gov hold no record (searched October 28, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
No human data exist. From the laboratory and animal work:
Contraindications & Cautions
Indolicidin is not a medicine, so there is no label or formal contraindication.
Legal Status
Indolicidin is a research peptide, approved nowhere.
Frequently Asked Questions
?What is indolicidin?
A 13-amino-acid antimicrobial peptide from the white blood cells of cattle, part of the cathelicidin family. Five of its 13 residues are tryptophan, the most of any known natural sequence.
?Can I take indolicidin?
No. It has never been tested in people and is not sold as a medicine. On its own it damages human red blood cells at the strengths that kill microbes.
?How does it kill microbes?
Two ways at once: it opens channels in the microbe's membrane, and it enters the cell and blocks DNA synthesis, which makes bacteria grow into long filaments.
?Is it the same as omiganan?
No. Omiganan is a redesigned analogue of indolicidin, built to keep the activity and reduce the toxicity, and it is the one that reached human trials. It has its own entry.
?Why isn't it a drug if it kills so much?
The same chemistry that breaks microbial membranes breaks human ones. In mice it was only usable when packaged in fat particles, and the field has moved to safer redesigned versions.
?Does it work against viruses?
In the laboratory it inactivated HIV, apparently by acting on the viral envelope, but at concentrations that also harmed human cells. This is test-tube work, not treatment.
References
- [pubmed] Selsted ME, et al. "Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils." J Biol Chem, 1992;267(7):4292-5. PMID: 1537821.
- [pubmed] Del Sal G, et al. "cDNA cloning of the neutrophil bactericidal peptide indolicidin." Biochem Biophys Res Commun, 1992;187(1):467-72. PMID: 1520337.
- [pubmed] Falla TJ, et al. "Mode of action of the antimicrobial peptide indolicidin." J Biol Chem, 1996;271(32):19298-303. PMID: 8702613.
- [pubmed] Subbalakshmi C, et al. "Mechanism of antimicrobial action of indolicidin." FEMS Microbiol Lett, 1998;160(1):91-6. PMID: 9495018.
- [pubmed] Hsu CH, et al. "Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA." Nucleic Acids Res, 2005;33(13):4053-64. PMID: 16034027.
- [pubmed] Subbalakshmi C, et al. "Requirements for antibacterial and hemolytic activities in the bovine neutrophil derived 13-residue peptide indolicidin." FEBS Lett, 1996;395(1):48-52. PMID: 8849687.
- [pubmed] Robinson WE Jr, et al. "Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils." J Leukoc Biol, 1998;63(1):94-100. PMID: 9469478.
- [pubmed] Lee DG, et al. "Fungicidal effect of indolicidin and its interaction with phospholipid membranes." Biochem Biophys Res Commun, 2003;305(2):305-10. PMID: 12745074.
- [pubmed] Ahmad I, et al. "Liposomal entrapment of the neutrophil-derived peptide indolicidin endows it with in vivo antifungal activity." Biochim Biophys Acta, 1995;1237(2):109-14. PMID: 7632702.
- [pubmed] Ghiselli R, et al. "Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis." Crit Care Med, 2008;36(1):240-5. PMID: 18090372.
- [pubmed] Vergis J, et al. "Antimicrobial Efficacy of Indolicidin Against Multi-Drug Resistant Enteroaggregative Escherichia coli in a Galleria mellonella Model." Front Microbiol, 2019;10:2723. PMID: 31849877.
- [pubmed] ALtameemi R, et al. "Synergistic Activity of Indolicidin and Tigecycline Against Multidrug-Resistant Acinetobacter Baumannii Clinical Isolates." Cell Physiol Biochem, 2025;59(1):92-99. PMID: 40033934.
- [pubmed] Shi Z, et al. "Indolicidin Attenuates Inflammation by Modulating the TLR4 Signaling Pathway during Sepsis Progression." ACS Infect Dis, 2026;12(7):2288-2302. PMID: 42305095.
- [review] Batista Araujo J, et al. "Indolicidin revisited: biological activity, potential applications and perspectives of an antimicrobial peptide not yet fully explored." World J Microbiol Biotechnol, 2022;38(3):39. PMID: 35018535.
- [review] Martín Bedoya JG, et al. "Nanosystems for delivery of indolicidin peptide." Front Med Technol, 2026;8:1845120. PMID: 42548778.
- [pubmed] Smirnova MP, et al. "Indolicidin analogs with broad-spectrum antimicrobial activity and low hemolytic activity." Peptides, 2020;132:170356. PMID: 32593681.
- [other] PubChem CID 90478486, Indolicidin: formula C100H132N26O13, molecular weight 1906.3. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/90478486
- [other] UniProt P33046: cathelicidin-4 (indolicidin), Bos taurus; peptide residues 131 to 143, ILPWKWPWWPWRR, with a C-terminal arginine amide. Read October 28, 2026. https://www.uniprot.org/uniprotkb/P33046/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026 (a title search for indolicidin returned 98 records, a broader search 257). Sequence from UniProt P33046 and formula from PubChem CID 90478486, read October 28, 2026. Status from Drugs@FDA, the EMA medicines list and ClinicalTrials.gov. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.