The Commensal Staphylococcus warneri Makes Peptide Inhibitors of MRSA Quorum Sensing that Protect Skin from Atopic or Necrotic Damage

Brown, Morgan M.; Cho, Young-Saeng; Manzer, Haider S; Bunch, Zoie L; Shahbandi, Ali; Todd, Daniel A.; Cech, Nadja B.; Horswill, Alexander R.

doi:10.1016/j.jid.2022.05.1092

Cited by 13 publications

(19 citation statements)

References 16 publications

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“…Another study showed that synthetic heterologous AIPs identified from Staphylococcus simulans isolated from humans and cattle were able to reduce dermonecrotic and epicutaneous skin lesions in mouse models of methicillin-resistant S. aureus (MRSA) skin infections by inhibiting all agr quorum sensing signalling subtypes ( 111 ). Similarly, several peptide quorum quenchers, including those from Staphylococcus warneri , Staphylococcus capitis , and Staphylococcus epidermidis , have potential as therapeutic agents in AD ( 110 , 112 , 113 ). Interestingly, apicidin, a cyclic fungal tetrapeptide, also inhibited all agr QS systems in methicillin-resistant S. aureus (MRSA), suggesting that there is competition within kingdoms that can be exploited in the discovery of new quorum quenching AMPs ( 114 ).…”

Section: Bacterial Amps In Admentioning

confidence: 99%

Microbial derived antimicrobial peptides as potential therapeutics in atopic dermatitis

et al. 2023

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Atopic dermatitis (AD) is a common chronic inflammatory skin disease that significantly affects the patient’s quality of life. A disrupted skin barrier, type 2 cytokine-dominated inflammation, and microbial dysbiosis with increased Staphylococcus aureus colonization are critical components of AD pathogenesis. Patients with AD exhibit decreased expression of antimicrobial peptides (AMPs) which is linked to increased colonization by Staphylococcus aureus. The skin microbiome itself is a source of several AMPs. These host- and microbiome-derived AMPs define the microbial landscape of the skin based on their differential antimicrobial activity against a range of skin microbes or their quorum sensing inhibitory properties. These are particularly important in preventing and limiting dysbiotic colonization with Staphylococcus aureus. In addition, AMPs are critical for immune homeostasis. In this article, we share our perspectives about the implications of microbial derived AMPs in AD patients and their potential effects on overlapping factors involved in AD. We argue and discuss the potential of bacterial AMPs as therapeutics in AD.

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Section: Bacterial Amps In Admentioning

confidence: 99%

Microbial derived antimicrobial peptides as potential therapeutics in atopic dermatitis

et al. 2023

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“…In S. epidermidis, one of the most abundant CoNS skin colonizers in which a functional agr system enhances skin colonization The square brackets denote amino acid residues within the AIP macrocycle. IC 50 values compiled from [37,128,[133][134][135][136]; NC, not calculated, likely to be a weak inhibitor; IA, not active at highest dose tested; -not available.…”

Section: Intra-and Inter-species Agr-mediated Competitive Interferenc...mentioning

confidence: 99%

“…simulans [134] and S. warneri [136]. These in vivo investigations facilitated quantification of the dose-dependent efficacy of the CoNS AIPs or the corresponding CoNS strain with respect to reducing MRSA skin colonization, lesion morphologies and sizes, weight loss, bacterial burden and skin barrier integrity.…”

Section: Introductionmentioning

confidence: 99%

“… The square brackets denote amino acid residues within the AIP macrocycle. IC 50 values compiled from [37, 128, 133–136]; NC, not calculated, likely to be a weak inhibitor; IA, not active at highest dose tested; – not available. …”

Section: Introductionmentioning

confidence: 99%

“… S. warneri AIP-2, which is more fivefold more potent in vitro than AIP-1, is one of the few naturally occurring AIPs that can inhibit S. aureus agr group IV [136]. The latter has been associated with scalded skin syndrome and the production of exfoliative toxins.…”

Section: Introductionmentioning

confidence: 99%

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Quorum-sensing, intra- and inter-species competition in the staphylococci

et al. 2023

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In Gram-positive bacteria such as Staphylococcus aureus and the coagulase-negative staphylococci (CoNS), the accessory gene regulator (agr) is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm development. Signalling via agr depends on the interaction of an autoinducing peptide (AIP) with AgrC, a transmembrane sensor kinase that, once phosphorylated activates the response regulator AgrA. This in turn autoinduces AIP biosynthesis and drives target gene expression directly via AgrA or via the post-transcriptional regulator, RNAIII. In this review we describe the molecular mechanisms underlying the agr-mediated generation of, and response to, AIPs and the molecular basis of AIP-dependent activation and inhibition of AgrC. How the environment impacts on agr functionality is considered and the consequences of agr dysfunction for infection explored. We also discuss the concept of AIP-driven competitive interference between S. aureus and the CoNS and its anti-infective potential.

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Cutibacterium and Staphylococcus dysbiosis of the skin microbiome in acne and its decline after isotretinoin treatment

Feidenhansl,

Lund,

Poehlein

et al. 2024

JEADV Clinical Practice

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BackgroundAcne vulgaris is a multifactorial disease of the pilosebaceous unit of human skin. Previous studies have identified an acne‐associated dysbiosis of the skin microbiome.ObjectivesThis dysbiosis was mainly determined for Cutibacterium acnes. However, detailed analyses combining qualitative and quantitative aspects are scarce, also regarding the possible contribution of other skin bacteria and the impact of treatment.MethodsWe conducted a culture‐independent study to determine differences between the healthy skin and the acne microbiome before and after isotretinoin treatment. Three amplicon‐based sequencing approaches and digital droplet PCR for quantification were applied.ResultsOur results revealed a 2.2‐fold reduced abundance of C. acnes with a reduced diversity in the acne microbiome. A phylotype switch was found, which was mainly characterized by a significant relative decrease of IB and II strains in the acne microbiome. In contrast, the relative abundance of staphylococci increased significantly and the quantitative ratio of staphylococci to C. acnes strongly increased from 1:34 in the healthy cohort to 1:11 in the acne cohort. The diversity of staphylococci was reduced, mainly due to the decrease of Staphylococcus hominis, and the appearance and predominance of Staphylococcus aureus in some acne patients. Isotretinoin treatment drastically depleted C. acnes (37‐fold) and moderately also staphylococci (3.6‐fold). Isotretinoin treatment resulted in a decrease of Staphylococcus epidermidis and a significant increase of S. aureus on facial skin.ConclusionsThe switch from a C. acnes‐dominated healthy skin microbiome towards an acne microbiome that is relatively enriched in staphylococci could indicate a stronger impact of staphylococci in the pathophysiology of acne than currently acknowledged. Our data further showed that isotretinoin largely eliminated the skin microbiome and in particular C. acnes, but also S. epidermidis. Instead, more harmful bacteria such as S. aureus could expand, suggesting that posttreatment strategies should be considered to accelerate skin microbiome recovery.

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The Commensal Staphylococcus warneri Makes Peptide Inhibitors of MRSA Quorum Sensing that Protect Skin from Atopic or Necrotic Damage

Cited by 13 publications

References 16 publications

Microbial derived antimicrobial peptides as potential therapeutics in atopic dermatitis

Microbial derived antimicrobial peptides as potential therapeutics in atopic dermatitis

Quorum-sensing, intra- and inter-species competition in the staphylococci

Cutibacterium and Staphylococcus dysbiosis of the skin microbiome in acne and its decline after isotretinoin treatment

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