610
J. Cosmet. Sci., 75.6, 610–625 (November/December 2024)
*Address all correspondence to Pascaline criton, pascaline.criton@sederma.fr.
A Pentapeptide to Control Cutibacterium Acnes Growth and
Activity
PASCALINE CRITON, PHILIPPE MONDON, ALBA CICO, CAMILLE SILOU,
CAROLE LE BACHELIER, AURELIEN PITOIS, PAULINE DIAZ, OLIVIER PESCHARD,
RICHARD LEROUX AND CAROLINE RINGENBACH
Sederma, Le Perray-en-Yvelines, France (P.C., P.M., A.C., C.S., C.B., A.P., P.D., O.P., R.L., C.R.)
Accepted for publication October 21, 2024.
Synopsis
Human-associated microbial communities have gained significant interest in both medical and cosmetic
fields. Understanding microbiota function and interactions has advanced considerably. Dysbiosis of commensal
microbiota is linked to skin disorders like psoriasis, dandruff, atopic dermatitis, and acne. Cosmetic actives
can reduce acne lesions’ negative aspects by acting upstream or downstream of their appearance. Peptides
are widely used to moderate wrinkles, spots, and improve skin barrier function. We identified a small
multifunctional peptide, palmitoyl-Lysyl-Threonyl-Seryl-Lysyl-Serine (pKTSKS) that inhibits Cutibacterium
acnes (C. acnes) growth both in-vitro and in-vivo without impacting Staphylococcus epidermidis (S. epidermidis).
pKTSKS inhibits C. acnes biofilms adhesion by 99 %and biofilm formation by 98 %.Reconstructed skin
models treated with pKTSKS have thicker outermost corneal skin layer (+186 %).Hyaluronic acid production
in keratinocytes was increased by 62 %.These data suggest that pKTSKS reinforces epidermal barrier and
skin moisture functions, both essential to a healthy skin. Additionally, pKTSKS reduces proinflammatory
mediator release, IL-1Ra production in keratinocytes co-cultured with C. acnes is increased by 283 %.In
fibroblasts, pKTSKS induces synthesis of collagen-I (+184 %)collagen -IV (+98 %)and fibronectin (+67 %).
In clinical studies pKTSKS reduced volume of inflammatory marks (-39.2 %),volume of pockmarks (-23 %)
and skin roughness (-8.1 %),resulting in smoother skin with improved appearance of inflammatory acne
lesions. This peptide offers a promising strategy to moderate the undesirable and psychologically detrimental
aspects of acne scarring.
INTRODUCTION
Skin and its microbial flora, also known as microbiota, form an ecosystem. Depending on
body site, skin microbiota hosts up to 1 million bacteria per cm². Skin microbiota also hosts
other microorganisms including fungi, archaea, viruses, and protists. Skin microbiota is
acquired during and after birth, and quickly evolves during the early months of life. While
the microbiota of people from the same family or professional group are notably similar,
every individual’s microbiota displays site-to-site variability. For instance, microbiota of the
armpits, a humid and warm zone, differs from the drier zones like the arms and legs, or of

611 Pentapeptide to Control Acne
the pilosebaceous zones that are invaginated, sebum-rich and oxygen-poor.1,2 It has been
largely documented that dysbiosis of microbiota in relation to physiological, environmental,
or behavioral modifications favor pathologies.3
Acne is one of the primary causes of dermatological consultations due to the potential
psychological distress caused by the associated scarring stigma it leaves on the skin. A
2020 study conducted on 4,000 people demonstrated that 78% of them claim to have
acne breakouts on a regular basis—on the cheeks, chin, forehead, nose, or on the upper
part of the body.4 In addition, more than 90% of teenagers undergo strong changes in
the appearance of their skin linked to an overproduction of sebum and Cutibacterium acnes
(C. acnes) proliferation.
C. acnes, formerly called Propionibacterium acnes and Corynebacterium acnes, is an anaerobic
gram-positive rod-shaped bacterium. It lives both at the upper part of the stratum corneum,
in contact with oxygen, and deeper into hair follicles, where it faces an environment rich in
sebum and proteins, but that is poor in oxygen.5–7 C. acnes represents 90% of the microbial
flora of the pilosebaceous follicle, yet C. acnes growth and virulence vary according to its
ribotype and the environment it lives in. This could explain why this commensal bacterium
is described with or without pro-acne properties.8
Bacteria sense environmental modifications which alter their behavior.9 They can
cluster together and reach a critical quantity, a quorum, that triggers more cell-to-cell
communications, thanks to increasing concentrations of secreted molecules or enzymes.
A consequence of bacterial clustering is the production of a biofilm. Biofilm isolates
and protects these cells from environmental insults such as antibiotics and host defense
mechanisms.10 Hence, preventing quorum from being reached helps to control biofilm
production.
C. acnes can switch from an isolated form to dense colonies, forming a biofilm in the
depression of hair follicles.11,12 In hair follicle sheath sections of acne-prone volunteers,
C. acnes generated more biofilms than in non-acne prone volunteer samples. The
biofilm therefore appears to contribute to the virulence of this bacterium. Both C. acnes
multiplication and biofilm formation disturb hair follicle sheath physiology through the
increasing of C. acnes lipase activities. Lipase is an extracellular enzyme responsible for
production of irritant-free fatty acids that cause local irritation. Consequences are the
increase of proinflammatory mediators, of matrix protease activities, and of pilosebaceous
ducts clogging,13–14 all damaging neighboring tissues at various depths. Acne exists in
several forms, with or without inflammatory features, redness, blemishes, comedones, or
scars. This creates significant skin damage and psychological distress, leading a significant
portion of people with acne to seek medical advice.
Several prescription-based treatments are used to moderate C. acnes activities and to restore
skin surface smoothness by reducing blemishes. However, these treatments have severe
side effects: facial erythema, hair loss, coronary heart disease, fetal development issues,
depression, clothes staining, and irritation. Peptides are molecules that can be tailored
to achieve desirable selective and potent biological activity. More than 60 peptide-based
therapeutics already exist on the market and hundreds are currently in developmental
stages for treatment of various diseases (type 2 diabetes, irritable bowel syndrome,
acromegaly), as selective or broad spectrum microbicidal agents, and anticancer agents.15
Since pioneering works on peptides years ago, the cosmetic industry widely and safely uses
small and well characterized peptides with anti-aging properties: dermal compartment