The Short Lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 Protect HaCaT Keratinocytes from Bacterial Damage Caused by Staphylococcus aureus Infection in a Co-Culture Model

Abstract

The search for new antimicrobial strategies is of major importance since there is a growing resistance of both bacteria and fungi to existing antimicrobials. Lipopeptides are promising and potent antimicrobial compounds. For translation into clinically useful molecules, effectiveness of peptide treatment against human infections must be proved in complex in vitro wound models. The aim of this study was to examine if the synthesized short lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 can protect HaCaT keratinocytes from bacterial damage caused by Staphylococcus aureus infection in a coculture model. After 1 h, 24 h, and 48 h incubation, cellular ATP level and release of the cytotoxicity marker LDH as well as the proinflammatory cytokines interleukin-6 and interleukin-1α were measured. Infection of the keratinocytes resulted in strong bacterial damage of HaCaT cells along with low cellular ATP levels and high release of LDH, IL-6, and IL-1α after 24 h and 48 h. Incubation of the infected human keratinocytes with (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 resulted in protection of the keratinocytes from bacterial damage caused by Staphylococcus aureus infection with ATP, LDH, IL-6, and IL-1α levels comparable to the untreated control. Hence, both synthesized lipopeptides are promising candidates with high therapeutic potential in dermatology for the treatment of topical infections.

Marine Fungal Cerebroside Flavuside B Protects HaCaT Keratinocytes against Staphylococcus aureus Induced Damage

“…An important role in this commensalism is played by glycosphingolipids of the skin barrier layer, which suppress the growth of pathogens. However, as soon as the protective properties of the skin are weakened, SA toxins have primarily a lytic effect on keratinocytes, destroying them in order to overcome the barrier and penetrate further [29]. As a result, SA caused an increase in the LDH release from infected cells, which was confirmed by our results.…”

Self-assembling short peptide amphiphiles as versatile delivery agents: a new frontier in antibacterial research

“…59,60 For instance, the lipopeptide (C 10 ) 2 -KKKK-NH 2 has displayed potent antibacterial properties against biofilms on surfaces like polystyrene and contact lenses, surpassing conventional antibiotics. 61 However, despite their efficacy, cationic amphiphiles like these pose concerns regarding their potential harm to human cells, reflecting the broader challenges faced by antimicrobial peptides (AMPs) and their derivatives. 62 High production costs, unfavorable pharmacokinetic profiles, and limited effectiveness in animal studies are among the obstacles encountered by these compounds.…”