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One hundred human-derived coagulase negative staphylococci (CoNS) were screened for antimicrobial activity using agar-based deferred antagonism assays with a range of indicator bacteria. Based on the findings of the screen and subsequent well assays with cell free supernatants and whole cell extracts, one strain, designated CIT060, was selected for...
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... bacterial indicator strains used in this study are listed in Table 1. Strains were grown in either Brain Heart Infusion (BHI) broth at 37˚C or in M17 broth supplemented with 0.5% glucose (GM17) at 30˚C as indicated in the Table 1. ...Similar publications
Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy vol...
Citations
... aureus have also been reported to resist the activity of proteinase K and trypsin [67], while capidermicin from Staph. capitis CIT060 was resistant to α-chymotrypsin and pepsin [68]. In this study, non-formylated M157 bacteriocins were completely inactivated by proteinase K while the N-formylated M157 bacteriocins, both the chemically synthesized and biosynthesized by Ent. ...
Enterococcus faecalis CAUM157 (KACC 81148BP), a Gram-positive bacteria isolated from raw cow’s milk, was studied for its bacteriocin production. The antimicrobial activity of CAUM157 was attributed to a two-peptide class IIb bacteriocin with potent activity against food-borne pathogen Listeria monocytogenes and periodontal disease-causing pathogens (Prevotella intermedia KCTC 15693 T and Fusobacterium nucleatum KCTC 2488 T). M157 bacteriocins exhibit high temperature and pH stability and resist hydrolytic enzyme degradation and detergent denaturation, potentially due to their structural conformation. Based on amino acid sequence, M157A and M157B were predicted to be 5.176 kDa and 5.182 kDa in size, respectively. However, purified bacteriocins and chemically synthesized N-formylated M157 peptides both showed 5.204 kDa (M157A) and 5.209 kDa (M157B) molecular mass, confirming the formylation of the N-terminal methionine of both peptides produced by strain CAUM157. Furthermore, the strain demonstrated favorable growth and fermentation with minimal bacteriocin production when cultured in whey-based media, whereas a 1.0% tryptone or soytone supplementation resulted in higher bacteriocin production. Although Ent. faecalis CAUM157 innately harbors genes for virulence factors and antimicrobial resistance (e.g., tetracycline and erythromycin), its bacteriocin production is valuable in circumventing the need for live microorganisms, particularly in food applications for pathogen control.
... Interestingly, ribosomally synthesized peptides of bacterial origin have received increased attention and hold great potential as valuable antimicrobial compounds against Communicated by Yusuf Akhter. a broad spectrum of multi-drug resistant (MDR) pathogens as well as therapeutic agents for the treatment of several diseases (Lynch et al. 2019;Magana et al. 2020;Mba and Nweze 2022;Telhig et al. 2022;García-Vela et al. 2023). Bacteriocins, which are antimicrobial peptides synthesized by bacteria have attracted increasing interest due to their high antimicrobial activities, stability, and low toxicity Lynch et al. 2019;Deslouches et al. 2020;Wiman et al. 2023). ...
... a broad spectrum of multi-drug resistant (MDR) pathogens as well as therapeutic agents for the treatment of several diseases (Lynch et al. 2019;Magana et al. 2020;Mba and Nweze 2022;Telhig et al. 2022;García-Vela et al. 2023). Bacteriocins, which are antimicrobial peptides synthesized by bacteria have attracted increasing interest due to their high antimicrobial activities, stability, and low toxicity Lynch et al. 2019;Deslouches et al. 2020;Wiman et al. 2023). The majority of bacteria synthesize at least one known or unknown bacteriocin (Riley and Wertz 2002;Meade et al. 2020;Darbandi et al. 2022). ...
Bacteriocins are highly diverse, abundant, and heterogeneous antimicrobial peptides that are ribosomally synthesized by bacteria and archaea. Since their discovery about a century ago, there has been a growing interest in bacteriocin research and applications. This is mainly due to their high antimicrobial properties, narrow or broad spectrum of activity, specificity, low cytotoxicity, and stability. Though initially used to improve food quality and safety, bacteriocins are now globally exploited for innovative applications in human, animal, and food systems as sustainable alternatives to antibiotics. Bacteriocins have the potential to beneficially modulate microbiota, providing viable microbiome-based solutions for the treatment, management, and non-invasive bio-diagnosis of infectious and non-infectious diseases. The use of bacteriocins holds great promise in the modulation of food microbiomes, antimicrobial food packaging, bio-sanitizers and antibiofilm, pre/post-harvest biocontrol, functional food, growth promotion, and sustainable aquaculture. This can undoubtedly improve food security, safety, and quality globally. This review highlights the current trends in bacteriocin research, especially the increasing research outputs and funding, which we believe may proportionate the soaring global interest in bacteriocins. The use of cutting-edge technologies, such as bioengineering, can further enhance the exploitation of bacteriocins for innovative applications in human, animal, and food systems.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00203-024-03948-y.
... This study screened a bank of CoNS against clinical isolates of MRSA in an at tempt to identify antimicrobial producers with activity against this specific pathogen Twenty-one MRSA isolates were used to reduce the likelihood that natural variations in antimicrobial susceptibility amongst the S. aureus strains would result in a putative anti microbial producer being overlooked. Unlike many other bacteriocin investigations which screen CoNS against a broad range of indicators or a specific sensitive indicato during the preliminary testing [36,[38][39][40], this investigation took a more directed ap proach with a single target pathogen in mind. ...
... While approximately 24% of CoNS isolates prevented the growth of a least one MRSA indicator, all 37 caused large zones in the growth of M. luteus. A simila investigation by Lynch et al., which also sought to evaluate the antimicrobial potential o CoNS, found that 94 of 100 isolates within a bank could inhibit the growth of at least one of the 24 indicators utilized [36]. Again, a separate investigation of bioactivity undertaken by Janek et al. noted a high degree of inhibition by a bank of 89 CoNS isolates obtained from the nares of healthy volunteers. ...
... CoNS are common colonizers of the human skin and nares. Along with exerting some probiotic effects on the skin through quorum sensing [20,21], interactions with the host immune system [31][32][33], and the secretion of antimicrobial enzymes [34,35], human-derived CoNS have been characterized as the producers of a variety of bacteriocins which when purified, have expressed clinically relevant bioactivity [14,36,37]. Given the relatedness of CoNS to their coagulase-positive counterparts and the targeted nature of bacteriocins, it is logical that CoNS-derived bacteriocins could be applied as a treatment against S. aureus. ...
Staphylococcus aureus is frequently highlighted as a priority for novel drug research due to its pathogenicity and ability to develop antibiotic resistance. Coagulase-negative staphylococci (CoNS) are resident flora of the skin and nares. Previous studies have confirmed their ability to kill and prevent colonization by S. aureus through the production of bioactive substances. This study screened a bank of 37 CoNS for their ability to inhibit the growth of methicillin-resistant S. aureus (MRSA). Deferred antagonism assays, growth curves, and antibiofilm testing performed with the cell-free supernatant derived from overnight CoNS cultures indicated antimicrobial and antibiofilm effects against MRSA indicators. Whole genome sequencing and BAGEL4 analysis of 11 CoNS isolates shortlisted for the inhibitory effects they displayed against MRSA led to the identification of two strains possessing complete putative bacteriocin operons. The operons were predicted to encode a nukacin variant and a novel epilancin variant. From this point, strains Staphylococcus hominis C14 and Staphylococcus epidermidis C33 became the focus of the investigation. Through HPLC, a peptide identical to previously characterized nukacin KQU-131 and a novel epilancin variant were isolated from cultures of C14 and C33, respectively. Mass spectrometry confirmed the presence of each peptide in the active fractions. Spot-on-lawn assays demonstrated both bacteriocins could inhibit the growth of an MRSA indicator. The identification of natural products with clinically relevant activity is important in today’s climate of escalating antimicrobial resistance and a depleting antibiotic pipeline. These findings also highlight the prospective role CoNS may play as a source of bioactive substances with activity against critical pathogens.
... Both S. lugdunensis and lugdunin alone can reduce S. aureus nasal carriage (15). Additionally, common skin commensals Staphylococcus epidermidis (16), Staphylococcus hominis (17), and Staphylococcus capitis (18) have all been shown to have antagonistic activity against S. aureus. Cutibacterium acnes produces a thiopeptide antibiotic, cutimycin, which inhibits staphylococcal species to shape the hair follicle microbiome (19). ...
Colonization of human skin and nares by methicillin-resistant Staphylococcus aureus (MRSA) leads to the community spread of MRSA. This spread is exacerbated by the transfer of MRSA between humans and livestock, particularly swine. Here, we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial species Desemzia incerta , which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in an in vivo murine skin model. Using parallel genomic and biochemical investigation, we discovered that D. incerta secretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis of D. incerta and MRSA cocultures, we found that exposure to D. incerta leads to decreased MRSA biofilm production. These results emphasize the value of exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as an increased understanding of microbial competition.
IMPORTANCE
Methicillin-resistant Staphylococcus aureus (MRSA) causes a significant healthcare burden and can be spread to the human population via livestock transmission. Members of the skin microbiome can prevent MRSA colonization via a poorly understood phenomenon known as colonization resistance. Here, we studied the colonization resistance of S. aureus by bacterial inhibitors previously identified from a porcine skin model. We identify a pig skin commensal, Desemzia incerta , that reduced MRSA colonization in a murine model. We employ a combination of genomic, proteomic, and transcriptomic analyses to explore the mechanisms of inhibition between D. incerta and S. aureus . We identify 24 candidate antimicrobial proteins secreted by D. incerta that could be responsible for its antimicrobial activity. We also find that exposure to D. incerta leads to decreased S. aureus biofilm formation. These findings show that the livestock transmission of MRSA can be exploited to uncover novel mechanisms of MRSA colonization resistance.
... A wide range of bacteriocins produced by S. epidermidis have already been described, such as Epidermin, Pep5, and Epilancin K7, which can affect different Gram-positive bacteria, including MRSA, other coagulasenegative Staphylococcus species (CoNS), and even S. epidermidis strains that do not produce these bacteriocins [14]. Another CoNS, S. capitis, was reported to produce a bacteriocin called capidermicin, which showed antimicrobial activity against all of the tested Grampositive bacteria (Lactococcus latis, S. aureus, Staphylococcus intermedius, Staphylococcus pseudintermedius, and Micrococcus luteus) [21]. Recently, Fernandéz-Fernandéz and colleagues (2022) tested the production of bacteriocin-like inhibitory substances (BLIS) from staphylococci of different sources. ...
The skin is the largest human organ and is responsible for many important functions, such as temperature regulation, water transport, and protection from external insults. It is colonized by several microorganisms that interact with each other and with the host, shaping the microbial structure and community dynamics. Through these interactions, the skin microbiota can inhibit pathogens through several mechanisms such as the production of bacteriocins, proteases, phenol soluble modulins (PSMs), and fermentation. Furthermore, these commensals can produce molecules with antivirulence activity, reducing the potential of these pathogens to adhere to and invade human tissues. Microorganisms of the skin microbiota are also able to sense molecules from the environment and shape their behavior in response to these signals through the modulation of gene expression. Additionally, microbiota-derived compounds can affect pathogen gene expression, including the expression of virulence determinants. Although most studies related to microbial interactions in the skin have been directed towards elucidating competition mechanisms, microorganisms can also use the products of other species to their benefit. In this review, we will discuss several mechanisms through which microorganisms interact in the skin and the biotechnological applications of products originating from the skin microbiota that have already been reported in the literature.
... Both S. lugdunesis and lugdunin alone can reduce S. aureus nasal carriage 15 . Additionally, common skin commensals S. epidermidis 16 , S. hominis 17 , and S. capitis 18 have all been shown to have antagonistic activity against S. aureus. Cutibacterium acnes produces a thiopeptide antibiotic, cutimycin, which inhibits staphylococcal species to shape the hair follicle microbiome 19 . ...
Colonization of human skin and nares by methicillin-resistant Staphylococcus aureus (MRSA) leads to community spread of MRSA. This spread is exacerbated by transfer of MRSA between humans and livestock, particularly swine. Here we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial species Desemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in an in vivo murine skin model. Using parallel genomic and biochemical investigation, we discovered that D. incerta secretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis of D. incerta and MRSA cocultures, we found that exposure to D. incerta leads to decreased MRSA biofilm production. These results emphasize the value in exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as increased understanding of microbial competition.
... After 24 h of contact, a dose-dependent decrease in IPEC-1 cell viability was observed when exposed to EntDD14. At concentrations of 50 µg·mL −1 and 100 µg·mL −1 , reductions of 9.6% and 20% in cell viability were noted, respectively [32]. The cytotoxic effect of EntDD14 on two cell lines of human origin, intestinal Caco-2 cells, and HT29 mucus-producing cells was studied [76]. ...
Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin (LLB) produced by Enterococcus faecalis 14, a human strain isolated from meconium. Studies performed on EntDD14 enabled it to show its activity against Gram-positive bacteria such as Listeria monocytogenes, Clostridium perfringens, Enterococcus faecalis, and Staphylococcus aureus. EntDD14 was also shown to potentiate the activity of different antibiotics such as erythromycin, kanamycin, and methicillin when assessed against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo in the NMRI-F holoxenic mouse model. Additionally, EntDD14 has an antiviral activity and decreased the secretion of pro-inflammatory IL-6 and IL-8 in inflamed human intestinal Caco-2 cells. The genome of E. faecalis 14 was sequenced and annotated. Molecular tools such as Bagel4 software enabled us to locate a 6.7kb-EntDD14 cluster. Transport of EntDD14 outside of the cytoplasm was shown to be performed synergistically by a channel composed of two pleckstrin-homology-domain-containing proteins, namely DdE/DdF and the ABC transporter DdGHIJ. This latter could also protect the bacteriocinogenic strain against extracellular EntDD14. Here, we focus on academic data and potential therapeutic issues of EntDD14, as a model of two-peptide LLB.
... Within the last decades, several emerging therapeutic alternatives, including antimicrobial peptides, bacteriophages, nanomedicines, probiotics, phytochemicals, photodynamic light therapy, etc., are being explored as suitable alternatives to antibiotics [3][4][5][6]. Bacteriocins are antimicrobial peptides produced by bacteria, mainly of ribosomal synthesis [7] that have recently attracted immense interest due to their high antimicrobial activities and stability [8]. Bacteriocin production seems to be a common characteristic among microorganisms, and it has been reported that most bacteria synthesize at least one antimicrobial ...
... Over time, bacteriocin-producing staphylococcal isolates have been recovered from human skin and nasal microbiota. Among the well-described staphylococcins, we can highlight the Staphylococcin C55 [35,36], Bsa [37,38], Capidermicin [8], Endopeptidase ALE-1 [39], NisinJ [32,40], Nukacin IVK45 [41], Pep5 [42][43][44], Epidermicin NI01 [45], Epilancin 15X [46,47], Staphylococcin T (StT) [48], Hominicin [49,50], Lugdunin [51], and SWLP1 [19] bacteriocins. Moreover, the bacteriocins Epidermin [52][53][54][55][56] and Epicidin 280 [57] have been isolated from human clinical samples and an extensive number of bacteriocin-like-inhibitory-substances have also been detected in Staphylococcus of human origin, such as Staphylococcin BacR1 [58], Staphylococcin IYS2 [59], Staphylococcin Au-26 [60], Bac 201 [61], Staphylococcin 188 [62], Staphylococcin D91 [63], TE8 [64], and Hogocidinα/β [34] (Tables 1 and 2). ...
Novel and sustainable approaches are required to curb the increasing threat of antimicrobial resistance (AMR). Within the last decades, antimicrobial peptides, especially bacteriocins, have received increased attention and are being explored as suitable alternatives to antibiotics. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria as a self-preservation method against competitors. Bacteriocins produced by Staphylococcus, also referred to as staphylococcins, have steadily shown great antimicrobial potential and are currently being considered promising candidates to mitigate the AMR menace. Moreover, several bacteriocin-producing Staphylococcus isolates of different species, especially coagulase-negative staphylococci (CoNS), have been described and are being targeted as a good alternative. This revision aims to help researchers in the search and characterization of staphylococcins, so we provide an up-to-date list of bacteriocin produced by Staphylococcus. Moreover, a universal nucleotide and amino acid-based phylogeny system of the well-characterized staphylococcins is proposed that could be of interest in the classification and search for these promising antimicrobials. Finally, we discuss the state of art of the staphylococcin applications and an overview of the emerging concerns.
... S taphylococcus capitis is a commensal skin bacterium that belongs to the coagulasenegative staphylococci (CoNS). S. capitis can protect against and prevent pathogens, as well as participating in skin equilibrium in their commensal form with the secretion of beneficial metabolites (1)(2)(3)(4)(5). S. capitis CCSM0123 was isolated from the healthy facial skin of a Chinese man. ...
Staphylococcus capitis strain CCSM0123 was isolated from healthy facial skin. The complete genome of CCSM0123 was sequenced using a combination of Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) and Illumina sequencing. The assembled 2.5-Mbp genome consisted of one chromosome and four plasmids.
... Through the synthesis of antimicrobial compounds, the local commensal microbial communities also contribute to colonisation resistance. Coagulase negative Staphylococci have shown to suppress the growth of closely-related bacterial species by producing bacteriocins -extremely potent compounds which are heat-resistant and synthesised in ribosomes [40][41][42]. Bacteriocins are reported to be synthesised by various skin commensals. For instance, S. epidermidis are reported to generate a variety of bacteriocins and phenol-soluble modulins that selectively eradicate pathogenic bacteria however inactive towards S. epidermidis [43]. ...
Purpose of Review
Microbial infections in chronic wounds can often lead to lower-limb amputation, decrease in quality of life, and increase in mortality rate, and there is an unmet need to distinguish between pathogens and colonisers in these chronic wounds. Hence, identifying the composition of healthy skin microbiota, microbes associated with chronic wound and healing processes, and microbial interactions and host response in healing wounds vs. non-healing wounds can help us in formulating innovative individual-centric treatment protocols.
Recent Findings
This review highlights various metabolites and biomarkers produced by microbes that have been identified to modulate these interactions, particularly those involved in host–microbe and microbe–microbe communication. Further, considering that many skin commensals demonstrate contextual pathogenicity, we provide insights into promising initiatives in the wound microbiome research.
Summary
The skin microbiome is highly diverse and variable, and considering its importance remains to be a hotspot of medical investigations and research to enable us to prevent and treat skin disorders and chronic wound infections. This is especially relevant now considering that non-healing and chronic wounds are highly prevalent, generally affecting lower extremities as seen in diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Pathogenic bacteria are purported to have a key role in deferring healing of wounds. However, the role of skin microflora in wound progression has been a subject of debate. In this review, we discuss biomarkers associated with chronic wound microenvironment along with the relevance of skin microflora and their metabolites in determining the chronicity of wounds.
