P-113D

Summary

P-113D is a synthetic 12‑amino‑acid antimicrobial peptide that is the D‑amino‑acid mirror image of the histatin‑5 fragment P‑113. It displays broad‑spectrum activity against Candida species and bacteria such as Pseudomonas aeruginosa, retains potency in low‑ionic‑strength media, cystic‑fibrosis sputum, and in animal models of sepsis and gingivitis. The D‑configuration makes the peptide resistant to proteolysis, supporting its investigation for oral, topical, intravenous and inhaled use in conditions like oral candidiasis, chronic lung infection in cystic fibrosis, and periodontal disease.

Mechanism of Action

P-113D is a cationic peptide that binds to microbial membranes, disrupting membrane integrity and causing rapid cell death. In sepsis models it also binds bacterial endotoxin, lowering plasma endotoxin and TNF‑α levels, indicating an anti‑endotoxin effect. The all‑D amino‑acid composition prevents intracellular proteolytic cleavage, allowing the peptide to remain active in environments that inactivate L‑form peptides, such as sputum from cystic‑fibrosis patients.

What the Research Shows

In vitro, P-113D shows potent activity against Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae, with MICs comparable to the L‑form P‑113. Unlike P‑113, the D‑analogue retains activity in undiluted cystic‑fibrosis sputum and is resistant to proteolysis by Candida albicans. In rat models of P. aeruginosa sepsis, P‑113D reduced lethality, plasma endotoxin, and TNF‑α, performing similarly to polymyxin B and slightly less than imipenem. In a beagle gingivitis model, topical P‑113D lowered gingival inflammation and bleeding compared with placebo. No human clinical data are reported.

Reported Benefits

Evidence from laboratory and animal studies suggests that P‑113D can (1) kill Candida and key bacterial pathogens, (2) remain active in the complex sputum environment of cystic‑fibrosis patients, (3) reduce inflammatory mediators in sepsis, and (4) diminish plaque formation and gingival inflammation when applied topically. Its resistance to proteolysis may allow longer persistence at the site of application.

Limitations of the Evidence

All published data are limited to in vitro assays and animal models; no human trials have been conducted. Antimicrobial potency was modestly lower than that of imipenem in sepsis models, and efficacy in chronic lung infection has not been demonstrated clinically. Safety, optimal dosing, pharmacokinetics, and potential resistance development remain uncharacterized.

Safety Considerations

The cited studies did not report adverse events in rats or dogs, but safety in humans has not been evaluated. As a synthetic D‑amino‑acid peptide, immunogenicity and toxicity are unknown, and regulatory approval has not been granted. Caution is warranted until formal toxicology and clinical safety data become available.

How It Is Administered

P‑113D has been studied for intravenous injection in animal sepsis models, as a topical gel for gingival application, and as an inhaled formulation for potential chronic suppressive therapy in cystic‑fibrosis patients. Oral formulations have been explored in pre‑clinical contexts, but no specific dosage forms are approved.

Routes of Administration

Goals & Uses

• Broad-spectrum antifungal activityAntifungalModerate
• Biofilm disruptionAntimicrobialLow
• Broad‑spectrum antibacterial therapyAntibacterialLow
• Periodontal infection controlAntibacterialLow
• Oral candidiasis treatmentAntifungalModerate

Contraindications

• Known hypersensitivity to histatin peptidesAllergyHigh

Adverse Effects

• Taste disturbanceSensoryUncommonAltered sense of taste
• Local irritationDermatologicCommon
• Hypersensitivity reactionImmunologicRare
• Local oral irritationLocal ReactionUncommon

Drug Interactions

• Zinc-containing productsLow

Population Constraints

• Pediatric patientsAgeRelative
• Severely immunocompromised patients with systemic candidiasisDisease SeverityRelative
• Pregnant or lactating womenReproductiveRelative

Regulatory Status

• European UnionUnapprovedResearch use only.
• United StatesUnapprovedInvestigational peptide; no FDA approval.
• United KingdomUnknownNo MHRA approval identified.

No regulatory approval in any jurisdiction. Investigated in early-phase clinical trials for oral candidiasis in HIV-positive patients. Development has remained at investigational/research stage.

Evidence & Sources

• Anticandida activity is retained in P-113, a 12-amino-acid fragment of histatin 5
  Journal ArticleLowRothstein DM, et al.2001-01-01T00:00:00.000000Z
• Potential therapeutic role of histatin derivative P-113d in experimental rat models of Pseudomonas aeruginosa sepsis
  Journal ArticleLowCirioni O, et al.2004-01-01T00:00:00.000000Z
• P-113D, an antimicrobial peptide active against Pseudomonas aeruginosa, retains activity in the presence of sputum from cystic fibrosis patients
  Journal ArticleLowSajjan US, et al.2001-01-01T00:00:00.000000Z
• Internalisation and degradation of histatin 5 by Candida albicans
  Journal ArticleLowRuissen AL, et al.2003-01-01T00:00:00.000000Z
• Inhibition of experimental gingivitis in beagle dogs with topical salivary histatins
  Journal ArticleLowPaquette DW, et al.1997-01-01T00:00:00.000000Z

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