Exfoliative Toxin Research Articles

Nano-emulgel formulation of lemongrass extract (Cymbopogon citratus) as herbal–based topical drug for oral mucositis: A review

Background: Oral mucositis is a condition characterized by inflammation and ulceration of the oral mucosa, commonly affecting cancer patients undergoing chemotherapy or radiotherapy, with MRSA infection as a significant contributing factor. This condition impairs mucosal barrier function, increasing susceptibility to secondary infections, especially from MRSA, which thrives in the moist environment of the oral cavity. Secondary infections by MRSA exacerbate symptoms, delay healing, and complicate the clinical presentation of mucositis through the production of virulence factors like enterotoxins and exfoliative toxins. Purpose: Explaining the potential of lemongrass extract and its combination with nanoemulgel formulation as herbal intervention against oral mucositis. Method: A literature review of studies published within the past five years from sources like ResearchGate, ScienceDirect, PubMed, and Google Scholar. Result: Lemongrass extract comprises prominent amount of citral, emphasizing anti-inflammatory and antioxidant capabilities. Combination with nanoemulgel phase will provide stability and enhanced therapeutic capabilities of lemongrass extract into the targeted oral site. Conclusion: The formulation of lemongrass extract nanoemulgel equipped can be a futuristic solution as an over-the-counter drug for minimally invasive therapy of oral mucositis.

Understanding host's response to staphylococcal scalded skinsyndrome.

The aim of this review was to summarise the current knowledge on host-related factors that contribute to the development and severity of staphylococcal scalded skin syndrome (SSSS) in children. A comprehensive assessment and analysis of the existing literature on SSSS clinical features, pathogenesis and susceptibility factors. SSSS is a blistering skin disease caused by circulating exfoliative toxins (ETs) of Staphylococcus aureus (S. aureus), almost exclusively affecting infants, young children and immunocompromised individuals. ETs possess serine protease activity and target desmoglein-1 (Dsg-1) in the superficial epidermis. While the role of S. aureus ETs and site of action are well-described, other host factors such as impaired immune responses to ETs, poor renal clearance and genetic factors are crucial for the onset of and/or the severity of SSSS in children. The fate of desmosomal fractions after cleavage by ETs, as well as the role of dermal inflammatory cell infiltrates remain to be elucidated.

Staphylococcus pseudintermedius ST2660 isolated from a cat has strong biofilm-forming ability and increases biofilm formation at cat’s normal body temperature

Staphylococcus pseudintermedius has been isolated from dogs, cats, and horses and is also known as an emergent zoonotic agent. We administered orbifloxacin, a fluoroquinolone, to treat bacterial infections of cutaneous wounds caused by excessive grooming of the skin in contact with the subcutaneous port of the subcutaneous ureteral bypass (SUB) system in a cat. However, after 80 days of treatment, a severe abscess was observed in the wound and fluoroquinolone-resistant S. pseudintermedius was isolated from the abscess. The isolate was identified as a novel sequence type (ST) 2660 and contained genes for leukocidins (lukS and lukF), exfoliative toxin (siet), and biofilm regulation (icaA and icaD). The isolate was resistant to macrolide, lincosamide, fluoroquinolone, and tetracycline classes. In addition, the isolate had strong biofilm-forming ability which significantly increased with culturing at 39 °C compared with that at 37 °C, suggesting that the isolate prefers a cats’ body temperature as the optimal biofilm growth condition. Notably, the biofilms were increased in the presence of doxycycline with culturing at 39 °C. This study is the first report in Japan on the new sequence type of S. pseudintermedius isolated from a companion animal and clarifies the distinctive virulence of S. pseudintermedius.

Crystal structure of exfoliative toxin D from Staphylococcus aureus

Staphylococcus aureus exfoliative toxins (ETs) are serine proteases responsible for staphylococcal scalded skin syndrome. Four ETs, ETA, ETB, ETD, and ETE, have been identified, all of which cleave desmoglein-1. This study presents the crystal structure of ETD at 1.75 Å resolution. The protein exhibits a structure composed of two β-barrels and two α-helices as described in previous studies of ETs. A predicted model of ETD in complex with Ile380–Glu381–Gly382–Pro383 (IEGP), a segment of human desmoglein-1 (hDsg1), was constructed. Glu381 of hDsg1 was predicted to interact with as many as six amino acid residues in ETD, whereas two amino acid residues in ETD primarily constituted subsite S1′, and a space near subsite S1′ was noted. It is likely that polypeptide chains located near the IEGP segment in the predicted structure of hDsg1 bind to this space. The structure of loop D, which was predicted to participate in subsite S2′, in ETD was markedly different from those in other ETs.

Virulence and host specificity of staphylococci from Staphylococcus intermedius group of pigeon origin with an emphasis on Staphylococcus intermedius

The Staphylococcus intermedius group (SIG) includes coagulase-positive staphylococci commonly found in animals. The taxonomic classification within the SIG has evolved with molecular techniques distinguishing five species. Despite their similarities, these species exhibit varied host affinities, with unclear implications for virulence and host interaction.This study aimed to investigate the presence of coagulase-positive staphylococci in pigeons and to detect genes encoding for selected virulence factors in isolated strains. Another goal was to determine the adhesion capabilities of randomly selected pigeon S. intermedius, S. delphini, and canine S. pseudintermedius strains to canine and pigeon corneocytes and their adhesion and invasion abilities to canine keratinocytes in vitro.In total, 121 coagulase-positive strains were isolated from domestic and feral pigeons. The most prevalent species were S. delphini B and S. intermedius in domestic and feral pigeons, respectively. We proved that pigeon strains carried genes encoding for exfoliative toxin SIET and leukotoxin Luk-I. Moreover, we found that S. intermedius showed higher adherence to pigeon than to canine corneocytes, aligning with its presumed natural host. No difference in adherence abilities of S. pseudintermedius to canine and pigeon corneocytes was observed. In this study, we also observed that S. pseudintermedius could successfully invade the canine keratinocytes, in contrary to S. delphini and S. intermedius. Moreover, only S. intermedius was not able to invade canine keratinocytes at all.These findings highlight the complex interplay between SIG bacteria, and their hosts, underscoring the need for further research to understand the mechanisms of host adaptation and pathogenicity within this group.

Vaginal colonization with virulent and methicillin resistant Staphylococcus aureus among Ugandan women in Labour

BackgroundStaphylococcus aureus (S. aureus) often colonizes the human skin, upper respiratory and genital tracts. In the female genital tract, it can be passed on to the newborn during vaginal delivery leading to either ordinary colonization, or neonatal infections notably umbilical stump sepsis, scalded skin syndrome, arthritis, or bacteraemia/sepsis. These infections are mediated by staphylococcal virulence factors such as (i) Staphylococcal Enterotoxins A, B, C, D, and E encoded by the sea, seb, sec, sed, see genes, (ii) Exfoliative Toxins A and B encoded by the eta and etb genes, (iii) Toxic Shock Syndrome Toxin 1 (TSST-1) encoded by the tst gene, (iv) Panton-Valentine Leukocidin (PVL) encoded by the pvl gene, and (v) Hemolysins alpha and delta encoded by the hla and hld genes, respectively. We determined the prevalence of S. aureus possessing one or more virulence factor genes and of methicillin resistant Staphylococcus aureus (MRSA) in this population.MethodsThis was a cross-sectional study, which used 85 S. aureus isolates from the Chlorohexidine (CHX) clinical trial study in Uganda. The isolates had been obtained by culturing vaginal swabs (VS) from 1472 women in labour, frozen at minus 80oC, then thawed, sub-cultured, and tested for the selected virulence genes sea, seb, sec, sed, see eta, etb, tst, pvl, hla and hld, and for the methicillin resistance determining gene (mecA). Data were analyzed using SPSS version 20.ResultsOf the 85 S. aureus isolates 13 (15.3%) were positive for one or more virulence factor genes, as follows: pvl 9/85 (10.6%), hld 5/85 (5.9%), sea 1/85 (1.2%) and seb genes 1/85 (1.2%). The other virulence genes (sec, sed, see, eta, etb, hla and tst) were not detected in any of the isolates. MRSA was detected in 55.3% (47/85) of the isolates, but only two of these carried the pvl virulence gene.ConclusionThis study demonstrated that 15% of the S. aureus colonizing the female lower genital tract of mothers in labour in central Uganda carried one or more virulence genes, mostly pvl, indicating potential for newborn infection with S. aureus acquired in the maternal birth canal. More than half of the isolates were MRSA.

Molecular Docking and Dynamic Simulation Studies of Bioactive Compounds from Traditional Medicinal Compounds Against Exfoliative Toxin B from Staphylococcus aureus

Background Staphylococcal scalded skin syndrome (SSSS) is a dermatological condition caused by Staphylococcus aureus, characterized by exfoliative toxin B, and its increasing resistance to conventional antibiotics necessitates the search for new therapeutic options. Aim The study aimed to investigate the potential of traditional medicinal compounds (TMCs) as potential pharmaceuticals against SSSS using molecular-level research. Introduction Staphylococcus aureus, commonly known as S. aureus, is the main cause of SSSS. These infections are a major concern for public health because they are becoming resistant to antibiotics. There is an urgent need for new medications to effectively fight against this infection. The main objective of this study was to assess the interaction between TMC compounds and S. aureus exfoliative toxins ETA and ETB utilizing computational approaches. Materials and Methods The investigation selected TMC compounds based on their potential to combat S. aureus infections. To predict binding affinities with the ETB toxin, molecular docking simulations were performed using AutoDock and AutoDock Vina. In order to evaluate the stability and interaction dynamics with the toxins, the most promising compound was subjected to a 100 ns molecular dynamics simulation. Stability was evaluated through various methods. Results Liquiritin showed the highest binding affinity, with a docking score of −7.6 kcal/mol. MD simulation confirmed the complex’s stability, and the binding free energy of −17.76 kcal/mol indicated potent inhibitory activity against S. aureus ETB. Conclusion Liquiritin, a TMC, effectively inhibits S. aureus toxins ETB, with promising potential for treating SSSS and antibiotic-resistant infections, requiring further research.

Investigation on biofilm composition and virulence traits of S. pseudintermedius isolated from infected and colonized dogs.

Staphylococcus pseudintermedius, which is part of the skin microbiome of dogs, causes a variety of opportunistic infections. These infections may become more difficult to treat due to the formation of biofilm. The capacity of S. pseudintermedius to form biofilm, as well as the associated genes, has not been elucidated. This study evaluated the production and composition of S. pseudintermedius biofilm. Samples were collected from both infected dogs and asymptomatic dogs. Isolates were identified using mass spectrometry and Multiplex-PCR. Biofilm production and composition were assessed using a quantitative microtiter plate assay. The presence of ica operon genes and sps genes was investigated using conventional PCR. The investigation of Agr type and virulence genes was conducted in silico on 24 sequenced samples. All strains could produce strong biofilms, with most of the isolates presenting a polysaccharide biofilm. 63.6% of the isolates carried the complete ica operon (ADBC). All samples showed the presence of the genes spsK, spsA, and spsL, while the distribution of other genes varied. Agr type III was the most prevalent (52.2%). All sequenced samples carried the cytotoxins hlb, luk-S, luk-F, as well as the exfoliative toxins siet and se_int. No isolate displayed other exfoliative toxins. Only LB1733 presented a set of different enterotoxins (sea, seb, sec_canine, seh, sek, sel, and seq). Our findings suggest that S. pseudintermedius is a strong producer of biofilm and carries virulence genes.

Does Adjunctive Clindamycin Have a Role in Staphylococcus aureus Bacteremia? A Protocol for the Adjunctive Treatment Domain of the Staphylococcus aureus Network Adaptive Platform (SNAP) Randomized Controlled Trial.

The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin-positive isolate.

Whole genome sequencing and molecular epidemiology of methicillin-resistant Staphylococcus aureus isolated from patients with bacteraemia in Slovenia.

Data on the molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates from patients with bacteraemia in Slovenia are lacking. The aim of this study was to phenotypically and genotypically investigate 82 MRSA strains isolated from patients with bloodstream infections in central Slovenia between 2019 and 2022. Whole-genome sequencing of selected strains was performed to characterize the strains based on sequence typing, antimicrobial resistance, toxin, and virulence factors genes. Most MRSA carried SCCmec II (63.4%), followed by SCCmec IV (34.1%) and SCCmec V (2.5%). A high proportion of strains belonging to the ST225 lineage (45.1%) was observed, followed by ST97 (18.3%), ST2883 (15.9%), ST22 (9.8%), ST5 (3.7%), and the ST1, ST398 and ST45 lineages (2.4% each). Sixteen different spa types were identified, predominantly ST225-t003 (31.7%), ST97-t359 (15.9%), and ST2883-t4336 (14.6%). None of the strains carried Panton-Valentine leukocidin, exfoliative toxins, or toxic shock toxin. All MRSA strains were susceptible to linezolid, rifampicin, vancomycin, teicoplanin, and trimethoprim-sulfamethoxazole. MRSA strains were resistant to erythromycin, clindamycin, tetracycline and gentamicin, with a frequency of 74.4%, 74.4%, 8.5%, and 1.2%, respectively. This study demonstrates that bacteraemia in central Slovenia is caused by diverse MRSA lineages. Identification of newly emerged lineages should be followed in the future to detect changes in the molecular epidemiology of MRSA in our country.

Prevalence of Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta) gene within methicillin resistant and susceptible Staphylococcus aureus in an urban tertiary hospital: A molecular epidemiology pilot study

Background Staphylococcus aureus is well known to cause a multitude of clinical manifestations, from mild to severe bloodstream infections that could lead to death. Infections are common, either in community-acquired or hospital-acquired settings, and treatment remains a challenge due to methicillin-resistant Staphylococcus aureus (MRSA). The pathogenesis of S. aureus is mediated by several cell-surface and secreted virulence factors. The virulence factors discussed in this study are Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta). Identifying both pvl and eta gene may help in studying bacterial pathogenesis and biology thus creating possible therapeutic pathway or intervention. Our pilot study aimed to observe pvl and eta as virulence gene prevalence in a North Sumatera tertiary referral health center. Methods Our study was a descriptive-analytical observational study with a cross-sectional design in which we collected isolates over a single time period. The frequency of genes is reported as a percentage comparison between MRSA and methicillin-susceptible S. aureus (MSSA). Qualitative gene prevalence analysis was carried out using the polymerase chain reaction (PCR). Results Our results showed that from 38 MRSA sample isolates, 32 samples were found to be pvl-positive, or 84,3% of the total samples. From 40 MSSA sample isolates, one sample was found to be pvl-positive MSSA, or 97,5%. Regarding eta, from 38 MRSA sample isolates, 81,6% of the total sample did not have eta, while from 40 MSSA sample isolates, all samples were found to be positive for eta. We found that both pvl and eta were significantly more likely to be expressed in the MSSA strain. Conclusions Our study shows that pvl and eta are more likely expressed in MSSA strains than in MRSA strains in Indonesia.

Staphylococcal scalded skin syndrome in neonate: Another face of CA-MRSA.

Staphylococcal scalded skin syndrome (SSSS), also known as Ritter's disease, in its severe form occurs predominantly in infants and children. It is caused by infection with group II (often phage group 71) Staphylococcus aureus. The foci of infection include nasopharynx, less commonly umbilicus, urinary tract, superficial abrasion, conjunctivae, and blood. Staphylococci are non-motile, non-spore-forming, catalase-positive, gram-positive cocci that appear predominantly as grape-like clusters. Although this organism is frequently a part of normal human microbial flora, it can cause significant opportunistic infections under certain conditions such as when extremes of age groups are involved, the presence of indwelling medical devices, and intravenous (iv) drug abuse. Staphylococcus aureus may cause a variety of infectious manifestations ranging from relatively benign skin infections to life-threatening systemic illnesses. SSSS caused by S. aureus strains produces exfoliative toxins which result in the development of blisters, erythema, and desquamation. Here, we present a case of an 11-day-old neonate who was diagnosed with SSSS. The causative agent responsible for this syndrome was identified as methicillin-resistant Staphylococcus aureus (MRSA). The molecular characterization of the gene Panton-Valentine leukocidin (PVL) was done by polymerase chain reaction (PCR) and was detected positive for PVL which is a distinctive virulence factor seen almost in all of the community-acquired MRSA strains. The patient was discharged after parenteral clindamycin therapy with almost complete resolution of symptoms.

Occurrence and Characteristics of Toxigenic Staphylococcus aureus in Retail Foods in Iran.

Staphylococcus aureus causes various toxigenic and invasive diseases in humans worldwide. This study examined the prevalence, virulence genes, and antibiotic resistance of S. aureus isolates collected from 894 retail food samples in Ardabil, Iran. Staphylococcal cassette chromosome mec (SCCmec), spa, and multilocus sequence typing methods were employed to further investigate the molecular characteristics of methicillin-resistant S. aureus (MRSA) isolates. The results revealed that 11.18% (n = 100) of food samples exhibited contamination with S. aureus (10.50% methicillin-sensitive S. aureus [MSSA] and 0.67% MRSA). Notably, raw minced meat (29.41%), Faloodeh (25%), and Olivier salad (21.42%) emerged as the most frequently contaminated food items. Among the 100 isolates of S. aureus, 94% were characterized as MSSA, with the remaining 6% identified as MRSA. The highest resistance was observed for penicillin (12%). MRSA isolates exhibited significantly higher resistance rates. Seventy-nine percent of the isolates were positive for sea, 14% for seb, 8% for a sec, and 0% for sed enterotoxin-encoding genes. Sixteen percent of isolates harbored two or more staphylococcal enterotoxin genes, simultaneously. Moreover, 97%, 94%, 24%, and 22% of isolates were positive for hla, hld, tst, and pvl virulence-encoding genes, respectively. No isolate was positive for the exfoliative toxins encoding eta and etb genes. MRSA isolates belonged to CC8 (n = 4) and CC22 (n = 2). Isolates in CC8 belonged to lineage ST239-MRSA-III and spa type t030; the isolates in CC22 belonged to ST22-MRSA-IV and spa types t310 and t223. In conclusion, a relatively high proportion of our retail food samples were contaminated with S. aureus. The high incidence of isolates with toxigenic genes raises serious health concerns. Furthermore, the presence of MRSA lineages linked to humans suggests that retail foods may be contaminated with human origin.

Biofilm formation by Staphylococcus pseudintermedius on titanium implants

Osteomyelitis often involves Staphylococcus spp. as the isolated genus in domestic animal cases. Implant-related infections, frequently associated with biofilm-forming microorganisms like staphylococci species, necessitate careful material selection. This study assessed biofilm formation by Staphylococcus pseudintermedius on titanium nuts used in veterinary orthopaedic surgery. Biofilm quantification employed safranin staining and spectrophotometric measurement, while bacterial counts were determined in colony-forming units (CFU). Scanning Electron Microscopy (SEM) evaluated the biofilm morphology on the surface of titanium nuts. All samples had CFU counts. Absorbance values that evidence biofilm formation were observed in seven of the eight samples tested. SEM images revealed robust bacterial colonization, and significant extracellular polymeric substance production, and the negative control displayed surface irregularities on the nut. Whole genome sequencing revealed accessory Gene Regulator (agr) type III in six samples, agr IV and agr II in two each. Genes encoding hlb, luk-S, luk-F, siet, se_int, and the icaADCB operon were identified in all sequenced samples. Other exfoliative toxins were absent. Biofilm formation by S. pseudintermedius was detected in all samples, indicating the susceptibility of orthopaedic titanium alloys to adhesion and biofilm formation by veterinary species. The biofilm formation capacity raises concerns about potential post-surgical complications and associated costs.

Identification of the Enterotoxigenic Potential of Staphylococcus spp. from Raw Milk and Raw Milk Cheeses.

This study aimed to genotypic and phenotypic analyses of the enterotoxigenic potential of Staphylococcus spp. isolated from raw milk and raw milk cheeses. The presence of genes encoding staphylococcal enterotoxins (SEs), including the classical enterotoxins (sea-see), non-classical enterotoxins (seg-seu), exfoliative toxins (eta-etd) and toxic shock syndrome toxin-1 (tst-1) were investigated. Isolates positive for classical enterotoxin genes were then tested by SET-RPLA methods for toxin expression. Out of 75 Staphylococcus spp. (19 Staphylococcus aureus and 56 CoNS) isolates from raw milk (49/65.3%) and raw milk cheese samples (26/34.7%), the presence of enterotoxin genes was confirmed in 73 (97.3%) of them. Only one isolate from cheese sample (1.3%) was able to produce enterotoxin (SED). The presence of up to eight different genes encoding enterotoxins was determined simultaneously in the staphylococcal genome. The most common toxin gene combination was sek, eta present in fourteen isolates (18.7%). The tst-1 gene was present in each of the analyzed isolates from cheese samples (26/34.7%). Non-classical enterotoxins were much more frequently identified in the genome of staphylococcal isolates than classical SEs. The current research also showed that genes tagged in S. aureus were also identified in CoNS, and the total number of different genes detected in CoNS was seven times higher than in S. aureus. The obtained results indicate that, in many cases, the presence of a gene in Staphylococcus spp. is not synonymous with the ability of enterotoxins production. The differences in the number of isolates with genes encoding SEs and enterotoxin production may be mainly due to the limit of detection of the toxin production method used. This indicates the need to use high specificity and sensitivity methods for detecting enterotoxin in future studies.

Molecular Characteristics and Pathogenicity of Staphylococcus aureus Exotoxins.

Staphylococcus aureus stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to its roles as an infectious agent that causes a wide variety of diseases ranging from moderately severe skin infections to fatal pneumonia and sepsis. S. aureus produces a variety of exotoxins that serve as important virulence factors in S. aureus-related infectious diseases and food poisoning in both humans and animals. For example, staphylococcal enterotoxins (SEs) produced by S. aureus induce staphylococcal foodborne poisoning; toxic shock syndrome toxin-1 (TSST-1), as a typical superantigen, induces toxic shock syndrome; hemolysins induce cell damage in erythrocytes and leukocytes; and exfoliative toxin induces staphylococcal skin scalded syndrome. Recently, Panton-Valentine leucocidin, a cytotoxin produced by community-associated methicillin-resistant S. aureus (CA-MRSA), has been reported, and new types of SEs and staphylococcal enterotoxin-like toxins (SEls) were discovered and reported successively. This review addresses the progress of and novel insights into the molecular structure, biological activities, and pathogenicity of both the classic and the newly identified exotoxins produced by S. aureus.

Necrotic activity of ExhC from Mammaliicoccus sciuri is mediated by specific amino acid residues

Mammaliicoccus sciuri, a commensal and pathogenic bacterium of significant clinical and veterinary relevance, expresses exfoliative toxin C (ExhC), a specific glutamyl endopeptidase belonging to the chymotrypsin family as the principal virulence factor. However, unlike most members of this family, ETs are inactive against a wide range of substrates and possess exquisite specificity for desmoglein-1 (Dsg1), a cadherin-like adhesion molecule that is crucial to maintain tissue integrity, thereby preventing the separation of skin cells and the entry of pathogens. ExhC is of clinical importance since in addition to causing exfoliation in pigs and mice, it induces necrosis in multiple mammalian cell lines, a property not observed for other ETs. Previous experiments have implicated the ExhC79–128 fragment in causing necrosis. Site-directed mutagenesis of specific residues within this fragment were studied and led to the design of an ExhC variant containing four-point mutations (ExhCmut4) lacking necrotic potential but retaining nearly wild-type (wt) levels of enzymatic activity. Moreover, the determination of the ExhCwt and ExhCmut4 crystal structures identified the conformation in the necrosis-linked region. These results constitute an important step toward the understanding of the mechanisms underlying the necrotic and epidermolytic activity of ExhC.

Comprehensive Analysis of Scalded Skin Syndrome: Clinical Exploration, Underlying Pathophysiology and Advanced Therapeutic Approaches

Scalded skin syndrome, a rare but potentially serious dermatologic entity, stands as a clinical and scientific challenge in the contemporary medical field. This article proposes a comprehensive evaluation of this entity, covering clinical aspects, pathophysiological mechanisms and state-of-the-art therapeutic perspectives. The skin, as the most extensive organ of the human body, is prone to a diversity of pathologies, among which scalded skin syndrome emerges as a condition characterized by significant epidermal exfoliation, commonly evoked by staphylococcal exfoliative toxins. Despite its dramatic clinical presentation, its accurate diagnosis may require meticulous differential evaluation to discern it from other skin conditions with similar manifestations. From a pathophysiological perspective, cutaneous de-adhesion in scalded skin syndrome originates in the specific unbinding of intracellular adhesion molecules, leading to intraepidermal separation and ultimately intraepidermal blistering. The constantly evolving understanding of the molecular processes involved has led to innovative therapeutic approaches that go beyond mere suppression of the causative infection. In this comprehensive review, current and emerging therapeutic options are addressed, including intravenous immunoglobulin, immune response modulating agents, and therapies targeting dysfunctional molecular signaling cascades. In addition, the importance of supportive care and prevention of life-threatening complications, such as sepsis, is discussed. In summary, this article is intended as an essential resource for clinicians, researchers, and healthcare professionals interested in furthering the comprehensive understanding of scalded skin syndrome. The convergence of clinical, basic research, and advanced therapies is crucial to improve early detection, effective management, and prognostic outcomes in this complex dermatologic entity.

Novel peeling skin condition in neonatal Pacific walruses, Saint Lawrence Island, Alaska, USA.

We describe here a novel peeling skin condition (PSC) in 2 neonatal Pacific walruses (Odobenus rosmarus subsp. divergens). Macroscopically, calves had various degrees of peeling skin exacerbated by mechanical trauma. Lesions occurred in areas subject to friction: ventrum, fore- and hindflippers, and associated joints. Histopathologic features included pseudocarcinomatous epithelial hyperplasia with orthokeratotic hyperkeratosis. Bacterial cocci were present within the stratum corneum. A few intraepidermal clefts were present. Inflammation, epidermolysis, and vasculopathies were not observed. PCR assays were negative for vesivirus and for Staphylococcus aureus exfoliative and toxic shock syndrome toxins. Tissue samples were cultured and bacteria isolated and identified by MALDI-TOF MS as Carnobacterium maltaromaticum, Psychrobacter phenylpyruvicus, Globicatella sanguinis, Streptococcus phocae, Pseudomonas spp., Rahnella aquatilis, and Escherichia coli. Given the young age of the calves and their clinical presentation, congenital ichthyosis was suspected. No genetic differences were detected for sequenced portions of keratin genes (keratin gene K10) between diseased and normal walrus skin. This rare PSC in neonatal Pacific walruses is recognized as novel by indigenous Alaskan marine mammal hunters of the Bering Strait region. A comprehensive diagnostic work-up of future case materials is needed to characterize the underlying biochemical defect(s).

Prevalence of Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta) gene within methicillin resistant and sensitive Staphylococcus aureus in an urban tertiary referral hospital: A molecular epidemiology pilot study

Background: Staphylococcus aureus is well known to cause a multitude of clinical manifestations, from mild to severe bloodstream infections that could lead to death. Infections are common, either in community-acquired or hospital-acquired settings, and treatment remains a challenge due to methicillin-resistant Staphylococcus aureus (MRSA). The pathogenesis of S. aureus is mediated by several cell-surface and secreted virulence factors. The virulence factors discussed in this study are Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta). Our pilot study aimed to observe pvl and eta as virulence gene prevalence in a North Sumatera tertiary referral health center. Methods: Our study was a descriptive-analytical observational study with a cross-sectional design in which we collected isolates over a single time period. The frequency of genes is reported as a percentage comparison between MRSA and methicillin-sensitive S. aureus (MSSA). Qualitative gene prevalence analysis was carried out using the polymerase chain reaction (PCR). Results: Our results showed that from 38 MRSA sample isolates, six samples were found to be pvl-negative, or 15.7% of the total samples. From 40 MSSA sample isolates, one sample was found to be pvl-negative MSSA, or 0.025%. Regarding eta, from 38 MRSA sample isolates, 18.4% of the total sample did not have eta, while from 40 MSSA sample isolates, all samples were found to be positive for eta. We found that both pvl and eta were significantly more likely to be expressed in the MSSA strain. Conclusions: Our study shows that pvl and eta are more likely expressed in MSSA strains than in MRSA strains in Indonesia.