Efficient treatment and pre-exposure prophylaxis in rhesus macaques by an HIV fusion-inhibitory lipopeptide.

Two HIV fusion-inhibitory lipopeptides (LP-97 and LP-98) were designed with highly potent, long-acting antiviral activity. Monotherapy using a low dose of LP-98 sharply reduced viral loads and maintained long-term viral suppression in 21 SHIVSF162P3-infected rhesus macaques. We found that five treated monkeys achieved potential posttreatment control (PTC) efficacy and had lower viral DNA in deep lymph nodes, whereas monkeys with a stable viral rebound had higher viral DNA in superficial lymph nodes. The tissues of PTC monkeys exhibited significantly decreased quantitative viral outgrowth and fewer PD-1+ central memory CD4+ T cells, and CD8+ T cells contributed to virologic control efficacy. Moreover, LP-98 administrated as a pre-exposure prophylaxis (PrEP) provided complete protection against SHIVSF162P3 and SIVmac239 infections in 51 monkeys via intrarectal, intravaginal, or intravenous challenge. In conclusion, our lipopeptides exhibit high potential as an efficient HIV treatment or prevention strategy.

A mutualistic bacterium rescues a green alga from an antagonist.

Photosynthetic protists, known as microalgae, are key contributors to primary production on Earth. Since early in evolution, they coexist with bacteria in nature, and their mode of interaction shapes ecosystems. We have recently shown that the bacterium Pseudomonas protegens acts algicidal on the microalga Chlamydomonas reinhardtii. It secretes a cyclic lipopeptide and a polyyne that deflagellate, blind, and lyse the algae [P. Aiyar et al., Nat. Commun. 8, 1756 (2017) and V. Hotter et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2107695118 (2021)]. Here, we report about the bacterium Mycetocola lacteus, which establishes a mutualistic relationship with C. reinhardtii and acts as a helper. While M. lacteus enhances algal growth, it receives methionine as needed organic sulfur and the vitamins B1, B3, and B5 from the algae. In tripartite cultures with the alga and the antagonistic bacterium P. protegens, M. lacteus aids the algae in surviving the bacterial attack. By combining synthetic natural product chemistry with high-resolution mass spectrometry and an algal Ca2+ reporter line, we found that M. lacteus rescues the alga from the antagonistic bacterium by cleaving the ester bond of the cyclic lipopeptide involved. The resulting linearized seco acid does not trigger a cytosolic Ca2+ homeostasis imbalance that leads to algal deflagellation. Thus, the algae remain motile, can swim away from the antagonistic bacteria and survive the attack. All three involved genera cooccur in nature. Remarkably, related species of Pseudomonas and Mycetocola also act antagonistically against C. reinhardtii or as helper bacteria in tripartite cultures.

Identification of the lipodepsipeptide selethramide encoded in a giant nonribosomal peptide synthetase from a Burkholderia bacterium.

Bacterial natural products have found many important industrial applications. Yet traditional discovery pipelines often prioritize individual natural product families despite the presence of multiple natural product biosynthetic gene clusters in each bacterial genome. Systematic characterization of talented strains is a means to expand the known natural product space. Here, we report genomics, epigenomics, and metabolomics studies of Burkholderia sp. FERM BP-3421, a soil isolate and known producer of antitumor spliceostatins. Its genome is composed of two chromosomes and two plasmids encoding at least 29 natural product families. Metabolomics studies showed that FERM BP-3421 also produces antifungal aminopyrrolnitrin and approved anticancer romidepsin. From the orphan metabolome features, we connected a lipopeptide of 1,928 Da to an 18-module nonribosomal peptide synthetase encoded as a single gene in chromosome 1. Isolation and structure elucidation led to the identification of selethramide which contains a repeating pattern of serine and leucine and is cyclized at the side chain oxygen of the one threonine residue at position 13. A (R)-3-hydroxybutyric acid moiety decorates the N-terminal serine. Initial attempts to obtain deletion mutants to probe the role of selethramide failed. After acquiring epigenome (methylome) data for FERM BP-3421, we employed a mimicry by methylation strategy that improved DNA transfer efficiency. Mutants defective in selethramide biosynthesis showed reduced surfactant activity and impaired swarming motility that could be chemically complemented with selethramide. This work unveils a lipopeptide that promotes surface motility, establishes improved DNA transfer efficiency, and sets the stage for continued natural product identification from a prolific strain.

Metabolic engineering of "last-line antibiotic" colistin in Paenibacillus polymyxa.

Colistin, also known as polymyxin E, is a lipopeptide antibiotic used to treat infections caused by multidrug-resistant gram-negative bacteria. It is considered a "last-line antibiotic", but its clinical development is hindered by low titer and impurities resulting from the presence of diverse homologs in microbial fermentation. To ensure consistent pharmaceutical activity and kinetics, it is crucial to have high-purity colistin active pharmaceutical ingredient (API) in the pharmaceutical industry. This study focused on the metabolic engineering of a natural colistin producer strain to produce colistin with a high titer and purity. Guided by genome mining, we identified Paenibacillus polymyxa ATCC 842 as a natural colistin producer capable of generating a high proportion of colistin A. By systematically inactivating seven non-essential biosynthetic gene clusters (BGCs) of peptide metabolites that might compete precursors with colistin or inhibit colistin production, we created an engineered strain, P14, which exhibited an 82% increase in colistin titer and effectively eliminated metabolite impurities such as tridecaptin, paenibacillin, and paenilan. Additionally, we engineered the L-2,4-diaminobutyric acid (L-2,4-DABA) pathway to further enhance colistin production, resulting in the engineered strain P19, which boosted a remarkable colistin titer of 649.3 mg/L - a 269% improvement compared to the original strain. By concurrently feeding L-isoleucine and L-leucine, we successfully produced high-purity colistin A, constituting 88% of the total colistin products. This study highlights the potential of metabolic engineering in improving the titer and purity of lipopeptide antibiotics in the non-model strain, making them more suitable for clinical use. These findings indicate that efficiently producing colistin API in high purity directly from fermentation can now be achieved in a straightforward manner.

Inhibitory activity of bacterial lipopeptides against Fusarium oxysporum f.sp. Strigae.

This study investigated the influence of bacterial cyclic lipopeptides (LP; surfactins, iturins, fengycins) on microbial interactions. The objective was to investigate whether the presence of bacteria inhibits fungal growth and whether this inhibition is due to the release of bacterial metabolites, particularly LP. Selected endophytic bacterial strains with known plant-growth promoting potential were cultured in the presence of Fusarium oxysporum f.sp. strigae (Fos), which was applied as model fungal organism. The extracellular metabolome of tested bacteria, with a focus on LP, was characterized, and the inhibitory effect of bacterial LP on fungal growth was investigated. The results showed that Bacillus velezensis GB03 and FZB42, as well as B. subtilis BSn5 exhibited the strongest antagonism against Fos. Paraburkholderia phytofirmans PsJN, on the other hand, tended to have a slight, though non-significant growth promotion effect. Crude LP from strains GB03 and FZB42 had the strongest inhibitory effect on Fos, with a significant inhibition of spore germination and damage of the hyphal structure. Liquid chromatography tandem mass spectrometry revealed the production of several variants of iturin, fengycin, and surfactin LP families from strains GB03, FZB42, and BSn5, with varying intensity. Using plate cultures, bacillomycin D fractions were detected in higher abundance in strains GB03, FZB42, and BSn5 in the presence of Fos. Additionally, the presence of Fos in dual plate culture triggered an increase in bacillomycin D production from the Bacillus strains. The study demonstrated the potent antagonistic effect of certain Bacillus strains (i.e., GB03, FZB42, BSn5) on Fos development. Our findings emphasize the crucial role of microbial interactions in shaping the co-existence of microbial assemblages.

Potential anti-aging applications of microbial-derived surfactantsin cosmetic formulations.

The skin aging process is a complex interaction of genetic, epigenetic, and environmental factors, such as chemical pollution and UV radiation. There is growing evidence that biosurfactants, especially those of microbial origin, have distinct age-supportive effects through different mechanisms, such as stimulation of fibroblast growth, high antioxidant capacities, and favorable anti-inflammatory properties. With a growing financial contribution of more than 15 m€per year, microbial surfactants (MSs) display unique biological effects on the skin including improved cell mobility, better nutrient access, and facilitated cellular growth under harsh conditions. Their biodegradable nature, unusual surface activity, good safety profile and tolerance to high temperature and pH variations widen their potential spectrum in biomedical and pharmaceutical applications. MSs typically have lower critical micelle concentration (CMC) levels than chemical surfactants enhancing their effectiveness. As natural surfactants, MSs are considered possible "green" alternatives to synthetic surfactants with better biodegradability, sustainability, and beneficial functional properties. This review therefore aims to explore the potential impacts of MSs as anti-aging ingredients.

Size-Controlled Synthesis of Gold Nanoparticles Tethering Antimicrobial Peptides with Potent Broad-Spectrum Antimicrobial and Antibiofilm Activities.

New antimicrobials are urgently needed to combat the rising global health concern of antibiotic resistance. Antimicrobial peptides (AMPs) are one of the leading candidates as new antimicrobials since they target bacterial membranes and are therefore less prone to bacterial resistance. However, poor enzymatic stability, high production costs, and toxicity are drawbacks that limit their clinical use. Conjugation of AMPs to gold nanoparticles (NPs) may help to improve enzymatic stability and, thus, their overall antimicrobial efficiency. We did a one-pot synthesis of size-controlled (10 nm) gold NPs selectively conjugated to lipopeptides and determined their antibacterial activity. The conjugates exhibited potent (0.13-1.25 µM) antimicrobial activity against clinical isolates, including Gram-positive methicillin-resistant Staphylococcus aureus (S. aureus) ATCC33593, Gram-negative Escherichia coli (E. coli) CTX-M-14, multidrug-resistant Pseudomonas aeruginosa LESB58 and Acinetobacter baumannii ATCC19606, and showed promising activity (90% inhibition of initial biofilms and 80% reduction of preformed biofilms) against S. aureus and E. coli DH5α biofilms at low micromolar concentrations. The conjugates were stable in rat serum and not toxic to representative mammalian cell lines in vitro (≤64 µM) and in vivo (≤100 µM).

Production and characterization of the lipopeptide with anti-adhesion for oral biofilm on the surface of titanium for dental implants.

Titanium implants are subject to bacterial adhesion and peri-implantitis induction, and biosurfactants bring a new alternative to the fight against infections. This work aimed to produce and characterize the biosurfactant from Bacillus subtilis ATCC 19,659, its anti-adhesion and antimicrobial activity, and cell viability. Anti-adhesion studies were carried out against Streptococcus sanguinis, Staphylococcus aureus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Proteus mirabilis as the minimum inhibitory concentration and the minimum bactericidal concentration. Cell viability was measured against osteoblast and fibroblast cells. The biosurfactant was classified as lipopeptide, with critical micelle concentration at 40 µg mL- 1, and made the titanium surface less hydrophobic. The anti-adhesion effect was observed for Staphylococcus aureus and Streptococcus sanguinis with 54% growth inhibition and presented a minimum inhibitory concentration of 15.7 µg mL- 1 for Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans. The lipopeptide had no cytotoxic effect and demonstrated high potential application against bacterial biofilms.

Strategies for improving fengycin production: a review.

Fengycin is an important member of the lipopeptide family with a wide range of applications in the agricultural, food, medical and cosmetic industries. However, its commercial application is severely hindered by low productivity and high cost. Therefore, numerous studies have been devoted to improving the production of fengycin. We summarize these studies in this review with the aim of providing a reference and guidance for future researchers. This review begins with an overview of the synthesis mechanism of fengycin via the non-ribosomal peptide synthetases (NRPS), and then delves into the strategies for improving the fengycin production in recent years. These strategies mainly include fermentation optimization and metabolic engineering, and the metabolic engineering encompasses enhancement of precursor supply, application of regulatory factors, promoter engineering, and application of genome-engineering (genome shuffling and genome-scale metabolic network model). Finally, we conclude this review with a prospect of fengycin production.

Design of MERS-CoV entry inhibitory short peptides based on helix-stabilizing strategies.

Interaction between Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) protein heptad repeat-1 domain (HR1) and heptad repeat-2 domain (HR2) is critical for the MERS-CoV fusion process. This interaction is mediated by the α-helical region from HR2 and the hydrophobic groove in a central HR1 trimeric coiled coil. We sought to develop a short peptidomimetic to act as a MERS-CoV fusion inhibitor by reproducing the key recognition features of HR2 helix. This was achieved by the use of helix-stabilizing strategies, including substitution with unnatural helix-favoring amino acids, introduction of ion pair interactions, and conjugation of palmitic acid. The resulting 23-mer lipopeptide, termed AEEA-C16, inhibits MERS-CoV S protein-mediated cell-cell fusion at a low micromolar level comparable to that of the 36-mer HR2 peptide HR2P-M2. Collectively, our studies provide new insights into developing short peptide-based antiviral agents to treat MERS-CoV infection.

A Family of Cyclic Lipopeptides Found in Human Isolates of Bacillus Ameliorates Acute Colitis via Direct Agonism of Toll-Like Receptor 2 in a Murine Model of Inflammatory Bowel Disease.

BACKGROUND: The Bacillus-derived cyclic lipopeptides (surfactin, iturin, and fengycin) form potent Heterogeneous Lipopeptide Micelle (HeLM) complexes. HeLM is a small molecule that has been shown to have immunomodulatory effects. However, how HeLM regulates inflammation is not clear, moreover its application to Inflammatory Bowel Disease (IBD), specifically Ulcerative Colitis (UC), has not been tested before. AIMS: To use a murine model of IBD and determine the effects of HeLM and related molecular mechanisms of action. METHODS: Colitis was induced in mice by administration of 4% Dextran Sodium Sulfate. Three preparations were tested against negative and positive controls: Purified HeLM, the wild-type strain that produces it, and an isogenic mutant that does not produce HeLM. Clinical, biochemical, and histological scoring systems were used to assess the severity of colitis. RT-qPCR and cell cultures were used to determine the levels of molecular signaling. Fecal samples were processed for metagenomic analysis. RESULTS: Purified HeLM, and the wild-type strain, significantly decreased the severity of colitis as determined by the disease activity index (DAI), mouse colitis histology index (MCHI), fecal calprotectin, and colonic length. This effect was not seen in the mutant. HeLM was found to be an agonist to TLR-2, seemingly activating the Toll-Like Receptor 2/IL-10 pathway, with subsequent downregulation of inflammatory cytokines (TNF-α, IL-1ß, and IL-6). At higher concentrations HeLM inhibited lipopolysaccharide ligands from activating TLR-4. The reduction in colitis was not due to microbiome modulation, as had previously been hypothesized. CONCLUSION: Our results indicate that HeLM ameliorates colitis by TLR-2-induced IL-10 production and possibly via the inhibition of lipopolysaccharide.

A promising antifungal lipopeptide from Bacillus subtilis: its characterization and insight into the mode of action.

Emerging resistance of fungal pathogens and challenges faced in drug development have prompted renewed investigations into novel antifungal lipopeptides. The antifungal lipopeptide AF3 reported here is a natural lipopeptide isolated and purified from Bacillus subtilis. The AF3 lipopeptide's secondary structure, functional groups, and the presence of amino acid residues typical of lipopeptides were determined by circular dichroism, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The lipopeptide's low minimum inhibitory concentrations (MICs) of 4-8 mg/L against several fungal strains demonstrate its strong antifungal activity. Biocompatibility assays showed that ~ 80% of mammalian cells remained viable at a 2 × MIC concentration of AF3. The treated Candida albicans cells examined by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy clearly showed ultrastructural alterations such as the loss of the cell shape and cell membrane integrity. The antifungal effect of AF3 resulted in membrane permeabilization facilitating the uptake of the fluorescent dyes-acridine orange (AO)/propidium iodide (PI) and FUN-1. Using 1,6-diphenyl-1,3,5-hexatriene (DPH) and 4-(2-[6-(dioctylamino)-2-naphthalenyl] ethenyl)-1-(3-sulfopropyl) pyridinium inner salt (di-8-ANEPPS), we observed that the binding of AF3 to the membrane bilayer results in membrane disruption and depolarization. Flow cytometry analyses revealed a direct correlation between lipopeptide activity, membrane permeabilization (~ 75% PI uptake), and reduced cell viability. An increase in 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence demonstrates endogenous reactive oxygen species production. Lipopeptide treatment appears to induce late-stage apoptosis and alterations to nuclear morphology, suggesting that AF3-induced membrane damage may lead to a cellular stress response. Taken together, this study illustrates antifungal lipopeptide's potential as an antifungal drug candidate. KEY POINTS: • The studied lipopeptide variant AF3 displayed potent antifungal activity against C. albicans • Its biological activity was stable to proteolysis • Analytical studies demonstrated that the lipopeptide is essentially membranotropic and able to cause membrane dysfunction, elevated ROS levels, apoptosis, and DNA damage.

N-Desmethylmajusculamide B, a lipopeptide isolated from the Okinawan cyanobacterium Okeania hirsuta.

A new lipopeptide, N-desmethylmajusculamide B (1), was isolated from the Okinawan cyanobacterium Okeania hirsuta along with 2 known compounds majusculamide A (2) and majusculamide B (3). The planar structure of (1) was elucidated by a detailed analysis of mass spectrometry and nuclear magnetic resonance spectra. The absolute configurations of the amino acid residues were determined using Marfey's analysis. The configuration of C-16 in the α-methyl-ß-keto-decanoyl moiety was determined unambiguously to be S by conducting a semisynthesis of N-desmethylmajusculamide B from 3. The cytotoxicity against mouse L1210 leukemia cells was evaluated for majusculamides (1-3).

Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation.

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.

Nanoencapsulation enhances the antimicrobial and antioxidant stability of cyclic lipopeptides for controlling Fusarium graminearum.

Fusarium graminearum not only causes Fusarium head blight (FHB) on wheat but also produces fungal toxins that pose a serious threat to food safety. Biological control is one of the safe and most effective alternative methods. In this study, cyclic lipopeptides (CLPs) produced from Bacillus mojavensis B1302 were extracted and identified by LC-MS/MS. After preparing mesoporous silica nanoparticles-NH2 (MSNsN) and encapsulating CLPs, the characterization analysis showed that the interaction between CLPs and MSNsN enhanced the crystal structure of CLPs-MSNsN. The antimicrobial activity and antioxidant capacity of CLPs-MSNsN stored at 20 °C and 45 °C were decreased more slowly than those of free CLPs with increasing storage time, indicating the enhancement of the antimicrobial and antioxidant stability of CLPs. Moreover, the field control efficacy of long-term stored CLPs-MSNsN only decreased from 78.66% to 63.2%, but the efficacy of free CLPs decreased significantly from 84.34% to 26.01%. The deoxynivalenol (DON) content of wheat grains in the CLPs-MSNsN treatment group was lower than that in the free CLPs treatment group, which showed that long-term stored CLPs-MSNsN reduced the DON content in wheat grains. Further analysis of the action mechanism of CLPs-MSNsN on F. graminearum showed that CLPs-MSNsN could disrupt mycelial morphology, cause cell apoptosis, lead to the leakage of proteins and nucleic acids, and destroy the cell permeability of mycelia. This work puts a novel insight into the antimicrobial and antioxidant stability enhancement of CLPs-MSNsN through encapsulation and provides a potential fungicide to control F. graminearum, reduce toxins and ensure food safety.

Identification of Gonatophragmium mori Causing Mulberry Zonate Leaf Spot Disease and Characterization of Their Biological Enemies in Guangxi, China.

Mulberry zonate leaf spot disease (MZLSD) is an important fungal disease of mulberry trees, which seriously affects the productivity and quality of mulberry leaves. MZLSD has been widely reported in sericultural production areas in Guangxi, China, in recent years. In this study, the causal agent of MZLSD was isolated from symptomatic samples and identified as Gonatophragmium mori (Acrospermaceae) based on morphological characterization and molecular analyses using nucleotide sequences of the internal transcribed spacer (ITS) and large subunit ribosomal DNA (LSU rDNA). Pathogenicity tests confirmed that G. mori is the pathogen responsible for MZLSD. Furthermore, we isolated antagonistic endophytic bacteria (AEB) from healthy mulberry leaves. Plate confrontation experiments showed that the lipopeptide crude extracts (LPCE) of three endophytic bacteria can inhibit the growth of G. mori, and the diameter of the antibacterial circle reaches more than 60 mm when their concentration of LPCE is 200 mg/ml. Light microscopy and scanning electron microscopy revealed that LPCE caused drastic changes in mycelial morphology. Fluorescence microscopy and transmission electron microscopy showed that the LPCE-induced apoptosis-like cell death in G. mori hyphae. Finally, based on morphological and molecular features, we identified the three isolates as Bacillus subtilis DS07, B. subtilis DS32, and B. velezensis Q6, respectively. To our knowledge, this is the first time to identify G. mori by combining characterization and molecular analyses, and we provide timely information about the use of biocontrol agents for suppression of G. mori.

Improvement of lipopeptide production in Bacillus subtilis HNDF2-3 by overexpression of the sfp and comA genes.

Bacillus subtilis HNDF2-3 can produce a variety of lipopeptide antibiotics with lower production. To improve its lipopeptide production, three genetically engineered strains were constructed. The results of real-time PCR showed that the highest transcriptional levels of the sfp gene in F2-3sfp, F2-3comA and F2-3sfp-comA were 29.01, 6.65 and 17.50 times of the original strain, respectively, while the highest transcriptional levels of the comA gene in F2-3comA and F2-3sfp-comA were 10.44 and 4.13 times of the original strain, respectively. The results of ELISA showed that the malonyl-CoA transacylase activity of F2-3comA was the highest, reaching 18.53 IU/L at 24 h, the data was 32.74% higher than that of the original strain. The highest total lipopeptide production of F2-3sfp, F2-3comA and F2-3sfp-comA induced by IPTG at optimal concentration were 33.51, 46.05 and 38.96% higher than that of the original strain, respectively. The results of HPLC showed that iturin A production of F2-3sfp-comA was the highest, which was 63.16% higher than that of the original strain. This study laid the foundation for further construction of genetically engineered strains with high lipopeptide production.

Colistin: Lights and Shadows of an Older Antibiotic.

The emergence of antimicrobial resistance represents a serious threat to public health and for infections due to multidrug-resistant (MDR) microorganisms, representing one of the most important causes of death worldwide. The renewal of old antimicrobials, such as colistin, has been proposed as a valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to present several adverse toxic effects, its usage in clinical practice has been reconsidered due to its broad spectrum of activity against Gram-negative (GN) bacteria and its important role of "last resort" agent against MDR-GN. Despite the revolutionary perspective of treatment with this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In last years, several forward steps have been made in the understanding of the resistance determinants, clinical usage, and pharmacological dosage of this molecule; however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not yet well defined. In this review, we summarize the mode of action, the emerging resistance determinants, and its optimal administration in the treatment of infections that are difficult to treat due to MDR Gram-negative bacteria.

Computational Methods Reveal a Series of Cyclic and Linear Lichenysins and Surfactins from the Vietnamese Marine Sediment-Derived Streptomyces Strain G222.

The Streptomyces strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16S rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and in silico metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of in silico Elucidations). This dereplication strategy allowed the identification of an interesting cluster of a series of putative cyclic and linear lipopeptides of the lichenysin and surfactin families. Lichenysins (3-7) were isolated from the sub-fraction, which showed significant anti-biofilm activity against Pseudomonas aeruginosa MUC-N1. Their structures were confirmed by detailed 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC, TOCSY, ROESY) recorded in CD3OH, and their absolute configurations were determined using the modified Marfey's method. The isolated lichenysins showed anti-biofilm activity at a minimum concentration of 100 µM. When evaluated for antibacterial activity against a panel of Gram-positive and Gram-negative strains, two isolated lichenysins exhibited selective activity against the MRSA strain without affecting its growth curve and without membranotropic activity. This study highlights the power of the MS/MS spectral similarity strategy using computational methods to obtain a cross-validation of the annotated molecules from the complex metabolic profile of a marine sediment-derived Streptomyces extract. This work provides the first report from a Streptomyces strain of combined cyclic and linear lichenysins and surfactins, known to be characteristic compounds of the genus Bacillus.

Surfactin as an ingredient in cosmetic industry: Benefits and trends.

Surfactin is a natural surfactant almost exclusively produced by Bacillus species with excellent physical-chemical, and biological properties. Among innovative applications, surfactin has been recently used as an ingredient in formulations. The antibacterial and anti-acne activities, as well as the anti-wrinkle, moisturizing, and cleansing features, are some of the reasons this lipopeptide is used in cosmetics. Considering the importance of biosurfactants in the world economy and sustainability, their potential properties for cosmetic and dermatological products, and the importance of patents for technological advancement in a circular bioeconomy system, the present study aims to review all patents involving surfactin as an ingredient in cosmetic formulas. This review was conducted through Espacenet, wherein patents containing the terms "cosmetic" and "surfactin" in their titles, abstracts, or claims were examined. Those patents that detailed a specific surfactin dosage within their formulations were selected for analysis. All patents, irrespective of their publication date, from October 1989 to December 2022, were considered. Additionally, a comprehensive search was performed in the MEDLINE and EMBASE databases, spanning from their inception until the year 2023. This complementary search aimed to enrich the understanding derived from patents, with a specific emphasis on surfactin, encompassing its associated advantages, efficacy, mechanisms of action on the skin, as well as aspects related to sustainability and its merits in cosmetic formulations. From the 105 patents analysed, 75% belong to Japan (54), China (14), and Korea (9). Most of them were submitted by Asian companies such as Showa Denko (15), Kaneka (11) and Kao Corporation (5). The formulations described are mainly emulsions, skincare, cleansing, and haircare, and the surfactin dose does not exceed 5%. Surfactin appears in different types of formulas worldwide and has a high tendency to be used. Surfactin and other biosurfactants are a promising alternative to chemical ingredients in cosmetic formulations, guaranteeing skin health benefits and minimizing the impact on the environment.

OBJECTIF: La surfactine est un agent tensioactif naturel presque exclusivement produit par les espèces de Bacillus, qui présente d'excellentes propriétés physico­chimiques et biologiques. Parmi les applications innovantes, la surfactine a été récemment utilisée comme ingrédient dans les formulations. Les activités antibactériennes et anti­acnéiques, ainsi que les propriétés antirides, hydratantes et nettoyantes, sont quelques­unes des raisons pour lesquelles ce lipopeptide est utilisé dans les cosmétiques. Compte tenu de l'importance des biosurfactants pour l'économie mondiale et la durabilité, de leurs propriétés potentielles pour les produits cosmétiques et dermatologiques, et de l'importance des brevets pour les progrès technologiques dans un système de bioéconomie circulaire, la présente étude vise à passer en revue tous les brevets impliquant la surfactine en tant qu'ingrédient dans les formules cosmétiques. MÉTHODES: Cet examen a été mené en utilisant Espacenet, dans lequel les brevets contenant les termes « cosmétique ¼ et « surfactine ¼ dans leurs titres, résumés ou revendications ont été examinés. Les brevets détaillant un dosage spécifique de surfactine dans leurs formulations ont été sélectionnés pour l'analyse. Tous les brevets, quelle que soit leur date de publication, d'octobre 1989 à décembre 2022, ont été pris en compte. En outre, une recherche complète a été effectuée dans les bases de données MEDLINE et EMBASE, depuis leur création jusqu'à l'année 2023. Cette recherche complémentaire visait à enrichir la compréhension dérivée de brevets, en mettant l'accent sur la surfactine, ses avantages associés, son efficacité, ses mécanismes d'action sur la peau, ainsi que les aspects liés à la durabilité et ses mérites dans les formulations cosmétiques. RÉSULTATS: Sur les 105 brevets analysés, 75 % appartiennent au Japon (54), à la Chine (14) et à la Corée (9). La plupart d'entre eux ont été soumis par des sociétés asiatiques telles que Showa Denko (15), Kaneka (11) et Kao Corporation (5). Les formulations décrites sont principalement des émulsions, des soins de la peau, des nettoyants et des soins capillaires, et la dose de surfactine n'excède pas 5 %. CONCLUSIONS: La surfactine apparaît dans différents types de formules dans le monde et conserve une forte tendance à l'utilisation. La surfactine et d'autres biosurfactants sont une alternative prometteuse aux ingrédients chimiques dans les formulations cosmétiques, garantissant des bénéfices pour la santé de la peau et minimisant l'impact sur l'environnement.