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Severe cutaneous injuries may not heal spontaneously and may necessitate the use of supplementary therapeutic methods. Electrospun nanofibers possess high porosity and specific surface area, which provide the necessary microenvironment for wound healing. Here in, the nanofibers of Soluplus-soy protein isolate (Sol-SPI) containing mupirocin (Mp) were fabricated via electrospinning for wound treatment. The fabricated nanofibers exhibited water absorption capacities of about 300.83 ± 29.72% and water vapor permeability values of about 821.8 ± 49.12 g/m2 day. The Sol/SPI/Mp nanofibers showed an in vitro degradability of 33.73 ± 3.55% after 5 days. The ultimate tensile strength, elastic modulus, and elongation of the Sol/SPI/Mp nanofibers were measured as 3.61 ± 0.29 MPa, 39.15 ± 5.08 MPa, and 59.11 ± 1.94%, respectively. Additionally, 85.90 ± 6.02% of Mp loaded in the nanofibers was released in 5 days in vitro, and by applying the Mp-loaded nanofibers, 93.06 ± 5.40% and 90.40 ± 5.66% of S. aureus and E. coli bacteria were killed, respectively. Human keratinocyte cells (HaCat) demonstrated notable biocompatibility with the prepared nanofibers. Furthermore, compare to other groups, Sol-SPI-Mp nanofibers caused the fastest re-epithelialization and wound healing in a rat model. The findings of this study present a novel nanofiber-based wound dressing that accelerates the healing of severe skin wounds with the risk of infection. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is an important pathogen that causes mild to invasive infections in hospitals and the community. Although methicillinsusceptible Staphylococcus aureus (MSSA) isolates continue to cause different infections, there is no data on the genetic backgrounds of the MSSA colonizing or causing infections in Kuwait hospitals. This study aimed to investigate MSSA isolated from patients admitted to Kuwait hospitals for antibiotic resistance and genetic backgrounds to understand their clonal composition. Methods: Consecutive MSSA isolates were collected from single patients during two surveillance periods in 2016 and 2021 in 13 public hospitals. The isolates were characterized using antibiogram, staphylococcal protein A (spa) typing, DNA microarray analysis, and multilocus sequence typing (MLST) using standard protocols. Results: A total of 446 MSSA was cultured from different clinical samples in 2016 (n  =  240) and 2021 (n  =  206). All isolates were susceptible to vancomycin [minimum inhibitory concentration (MIC) ≤  2  mg/L], teicoplanin (MIC ≤2  mg/L), linezolid (MIC ≤4  mg/L), ceftaroline (MIC ≤2  mg/L), rifampicin, and mupirocin but were resistant to erythromycin (21.3%), clindamycin (14.0%), gentamicin (3.8%), kanamycin (10.5%), fusidic acid (27.0%), tetracycline (6.9%), trimethoprim (23.1%), and ciprofloxacin (35.2%). Molecular typing identified 155 spa types, dominated by t127 (15.0%), t084 (5.4%), t3841 (5.4%), t267 (2.4%), t442 (2.2%), t091 (2.2%), t021 (2.2%), and t003 (2.2%); 31 clonal complexes (CCs); and 56 sequence types (STs). The majority of the isolates (n  =  265; 59.4%) belonged to CC1 (20.6%), CC15 (10.9%), CC22 (5.1%), CC30 (7.6%), CC361 (10.1%), and CC398 (4.7%). Discussion: The MSSA isolates belonged to diverse genetic backgrounds dominated by CC1, CC15, CC22, CC30, CC361, and CC398. The distribution of MSSA clones in 2016 and 2021 showed the stability of these clones over time. The study provides the first comprehensive data on the clonal distribution of MSSA in Kuwait hospitals. [ABSTRACT FROM AUTHOR]

Background: Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity. Results: We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores. EJt4aqYa_PFzdC4ihACHg3 Video Abstract Conclusions: These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches. [ABSTRACT FROM AUTHOR]

Chronic non‐healing wounds pose significant challenges due to an elevated inflammatory response caused in part by bacterial contamination (Physiol Rev. 2019;99:665). These wounds lead to billions being spent in the health care system worldwide (N Engl J Med. 2017;376:2367, Int J Pharm. 2014;463:119). We studied the in‐vitro and in‐vivo antimicrobial effects of a multimodal wound matrix (MWM) against two common wound pathogens, Methicillin‐Resistant Staphylococcus aureus (MRSA USA300) and Pseudomonas aeruginosa ATCC 27312 (PA27312) (Int Wound J. 2019;16:634). The in‐vitro study conducted was a zone of inhibition test with the two microbes at 104 Log CFU/mL inoculated on Tryptic soy agar with 5% sheep blood (TSAII) plates. Treatments used were MWM, Mupirocin (Positive control for MRSA), Silver Sulfadiazine (Positive Control for PA), Petrolatum and Sterile Saline (both serving as Negative Controls). Treatments were allowed to diffuse into the agar for 3 h and then were incubated for 24 h at 37°C. The in‐vivo study utilized a deep dermal porcine wound model (22 × 22 × 3 mm) created on six animals. Three animals were inoculated with MRSA USA300 and the other three with PA27312 with each allowing a 72‐h biofilm formation. After 72 h, baseline wounds were assessed for bacterial concentration and all remaining wounds were treated with either MWM alone, Silver Treatment or Untreated Control. Wounds were assessed on days 4, 8 and 12 after treatment application for microbiological analysis. In‐vitro, MWM exhibited significant inhibition of MRSA USA300 and PA27312 growth when compared to negative controls (p ≤ 0.05). Likewise, in‐vivo, the MWM‐treated wounds exhibited a significant (p ≤ 0.05) bacterial reduction compared to all other treatment groups, especially on days 8 and 12 for both pathogens. MWM demonstrated promise in addressing colonized wounds with biofilms. Additional studies on MWM's benefits and comparisons with existing treatments are warranted to optimize wound care strategies (Adv Wound Care. 2021;10:281). [ABSTRACT FROM AUTHOR]

Introduction: Neonatal myiasis is a rare condition, with few reports available on the subject. Surgical management is recommended in some cases. In this study, we present the case of a 7-day-old male neonate with larvae in his scrotum who underwent surgery. Case presentation: A full-term 7-day-old male infant (Aryan race) was referred to a children's hospital. On the sixth day after birth, three 3–4 mm long larvae crawled out from his scrotum, with the number increasing over time. He was given intravenous antibiotics and topical mupirocin to combat secondary infections. The surgical treatment involved two steps: first, the larvae were extracted, and then the infection site was washed with betadine and hydrogen peroxide to help remove any possible remaining larvae. Conclusion: Scrotal myiasis is a rare disease that occurs in infants and requires immediate treatment. Surgical treatment is effective in removing dead or decaying larvae from a deep-seated location and washing the infection site to prevent secondary infection. [ABSTRACT FROM AUTHOR]

By combining mechanical treatment of aluminium alloy with subsequent surface modification using micro-arc oxidation (MAO) technology, zinc oxide (ZnO) oxide coatings were prepared, which achieved enhanced hydrophobic properties, excellent antibacterial activity and corrosion resistance. The coatings were oxidised at different MAO discharge intensities using different frequencies. All surfaces were subjected to determination of wettability, corrosion resistance and chemical stability at 1, 7, 14, and 28 days and antibacterial activity of the coatings against the bacterial population of Staphylococcus aureus, Escherichia coli with an evaluation of population inhibition after 24 h. The surfaces mechanically modified by blasting showed a hydrophobic character; their subsequent oxidation by MAO contributed to a significant increase in hydrophobic properties. The sample with the highest Zn content (1.1 wt%), prepared at an MAO source frequency of 222 Hz, i.e. at the most intense plasma discharge, showed the most significant chemical stability in simulated body fluid (SBF) and distilled water and showed the highest antibacterial activity after 24 h. Thus, blasting of aluminium alloy surfaces and their subsequent MAO in alkaline electrolyte allows to obtain oxide coatings with antibacterial, hydrophobic and corrosion-resistant properties with the possibility of their use on surfaces with potential occurrence of harmful bacteria. • Oxide layers on aluminium alloy were prepared in alkaline electrolyte. • Frequencies of 49, 95 and 222 Hz, blasting and MAO technology combination were used. • Mechanically modified layers and MAO coatings achieved hydrophobic properties. • ZnO-doped MAO coatings had antibacterial properties and higher corrosion resistance. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is a new update on the resistance profile, Macrolide–Lincosamide–Streptogramin B resistance mechanisms and biofilm formation in the Staphylococcus aureus isolated from health care workers (HCWs) nasal carriage at a children's teaching hospital in Babol (Northern Iran). Results: A total of 143 non-repetitive nasal swab samples were collected from volunteers, where 53.8% (n; 77/143) were HCWs, 33.6% (n; 48/143) medical students, and 12.6% (n; 18/143) resident students. The prevalence of nasal carriers of S. aureus was 22.4% (n; 32/143), among them, 40.6% (n; 13/32) were identified as methicillin-resistant Staphylococcus aureus (MRSA(carriers. Antimicrobial susceptibility testing showed that erythromycin (68.8%, n; 22/32) and ciprofloxacin (15.6%, n; 5/32) had the highest and lowest resistance rate, respectively. The frequency of resistance genes in the strains was as follows; ermC (n; 17/32, 53.1%), ermA (n; 11/32, 34.4%), ermB (n; 6/32, 18.7%), ereA (n; 3/32, 9.4%). Moreover, 50.0% (n; 16/32), 28.1% (n; 9/32) and 21.8% (n; 7/32) of isolates were strongly, weakly and moderately biofilm producer, respectively. Macrolides-lincosamides-streptogramins B (MLSB) antibiotic resistance among S. aureus isolates from HCWs nasal carriage have found significant prevalence rates throughout the globe. It is crucial to remember that the development of biofilms and MLS B antibiotic resistance are both dynamic processes. [ABSTRACT FROM AUTHOR]

The application properties such as foam property, electrolyte tolerance, antibacterial activity and antistatic performance of the mixed systems of a novel Gemini quaternary ammonium salt with quadra‐cationic sites (TC‐GS) and sodium fatty alcohol polyoxyethylene ether carboxylate (AE9CNa) at various molar fraction of TC‐GS (αTC‐GS), were investigated systematically. Results show that TC‐GS/AE9CNa mixed systems with different ratios form a homogeneous and transparent solution, which exhibits excellent foam stability and antibacterial activity. The foam volume of the mixed system remains nearly constant from 400 s to 1000 s, and even when TC‐GS is 10 mg/L in the mixed systems, the antibacterial rates against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) for 2 min. are all exceeded 99 %. The mixed systems of TC‐GS/AE9CNa at various αTC‐GS also demonstrate the superior electrolyte tolerance, their maximum tolerance of NaCl, CaCl2 and MgCl2 is severally beyond 270 g/L, 180 g/L and 180 g/L. In addition, both TC‐GS solution and the mixed systems have good antistatic properties, which can reduce the surface resistance of polyester fabric to ≤1010 Ω. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus is an identified pathogen involved in the recurrence of symptoms in patients with chronic rhinosinusitis with nasal polyps. We investigated the effectiveness of a topical ointment of mupirocin applied in the nasal vestibule in lessening symptom recurrence and improving the efficiency of functional endoscopic sinus surgery. Materials and Methods: Patients with chronic rhinosinusitis, nasal polyps, and a positive nostril culture for Staphylococcus aureus were included in a clinical trial. The right nostril was determined as the intervention group (applying mupirocin ointment) and the left as the control group (applying vitamin A ointment). Lund-Mackay radiological scores and Lund-Kennedy endoscopic scores were examined at the time of diagnosis and six months later. Results: Among 60 patients with chronic rhinosinusitis with nasal polyps, 91.6% were positive for nostril Staphylococcus aureus. Comparing the average of the diagnostic radiological and endoscopic scores with the follow-up values in both groups indicated a significant improvement after surgery (Pvalue= 0.001, 0.001). However, there was no significant difference in the radiological and endoscopic score improvements between the study and control groups (P-value > 0.56, 0.74). Conclusion: Nasal mupirocin administration following endoscopic sinus surgery cannot significantly prevent symptom recurrence in chronic rhinosinusitis with nasal polyps. [ABSTRACT FROM AUTHOR]

Chitosan-based biomaterials are being investigated for their unique properties that support skin regeneration and wound healing. This study focused on the preparation and characterization of a mupirocin (Mup)-loaded PEGylated chitosan (CS-PEG) nanoparticulate film (NF) [CBNF]. The CBNF was characterized using FTIR spectroscopy and SEM analysis. The results demonstrated that CBNF was successfully incorporated into the composites, as shown by functional group modification through FTIR analysis. Additionally, the SEM micrograph revealed the deposition of nanoparticles (<200 nm) on the surface of transparent CBNF. The film has higher water absorption (≥1700%) and moderate water retention ability within 6 h. Furthermore, histological findings showed significant development, with re-epithelialization and granulation of tissues after 19 days, indicating the healing efficiency of CNBF. These results suggest that drug-loaded films could be an effective carrier and delivery agent for Mup-like anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments. Nano-mupirocin may offer such a selective treatment. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. In-depth characterization of this novel formulation was performed, and the main findings include: (i). the pharmacokinetic analysis of mupirocin administered as Nano-mupirocin vs mupirocin lithium (free drug) demonstrated that most of the Nano-mupirocin in plasma is liposome associated; (ii). microbiome analysis of rat feces showed no significant short-term difference between Nano-mupirocin, mupirocin lithium and controls; (iii). Nano-mupirocin was active against intratumoral F. nucleatum , a tumor promoting bacteria that accumulates in tumors of the AT3 mice model of breast cancer. These data suggest the ability of Nano-mupirocin to target tumor residing and promoting bacteria. Nano-mupirocin may offer a selective tumor-targeting antibiotic. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study is to develop and evaluate an ethosomal gel formulation of ciprofloxacin. It aims to provide a topical treatment for many bacterial infections that affect the skin. Administration of medications topically having the facility of delivering a high concentration of the drug to the skin than would be possible with systemic therapy. Topical administration of drugs is better for local action and the efficiency of the topically administered drug is increased with liposome, proliposomes and ethosomes. Recently, it was found that ethosomal carriers were phospholipid vesicular systems having relatively high concentrations of alcohol, enhances dermal and transdermal delivery of both lipophilic as well as hydrophilic molecules. Ciprofloxacin hydrochloride is a second-generation antibiotic and a BCS class II drug. Ethosomes were formulated using phospholipid, cholesterol, ethanol, polyethylene glycol and purified water by cold method. Ethosomes were evaluated for vesicle size, shape, optical microscopy, entrapment efficiency and in-vitro release study. F4 have better drug entrapment efficiency than the other formulation. The best formulation (F4) was used to prepare gel by using carbopol 934 as a gelling agent. The ethosomes were entrapped in gel matrix of carbopol 980 in different concentration 0.5%, 1.00% and 2% w/w. FT-IR studies revealed no interaction between the drug and excipients. The formulated gel formulation was evaluated with parameter pH, viscosity, spreadability, in-vitro release test, wash ability, extrudability study and stability studies. The formulation EGF2 have better in-vitro drug release profile which contains carbopol 980 concentration 1%w/w. the stability studies performed (EGF2) at refrigeration temperature (4.0±0.2°C), at room temperature (25-28±2°C) and 45±1°C for 45days. These ethosomes were unstable at higher temperature like 45.2°C. Percent efficiency of ethosomes also decrease at higher temperature like 4502°C. The present work also focuses on making the formulation more pharmaceutically acceptable. [ABSTRACT FROM AUTHOR]

Mupirocin, an antibiotic produced by Pseudomonas fluorescens, is mainly used for the topical treatment of various skin and soft tissue infections caused by Staphylococcus (including methicillin-resistant Staphylococcus aureus) and Streptococcus around the world for decades. Nevertheless, the clinical application scope of mupirocin varies in different countries due to differences in their medical policies, prescription types, and drug resistance. According to the experience of Chinese doctors in the past few years, mupirocin presented low drug resistance rates, and could be used as a treatment option for various primary infections and secondary infections, with antibacterial effects in a broad application. In this review, we summarized the experience of mupirocin used in the Chinese population and discussed its clinical value to provide novel insights and inspiration for physicians. [ABSTRACT FROM AUTHOR]

Purpose: Biofilms significantly contribute to the persistence and antibiotic resistance of Staphylococcus aureus infections. However, the regulatory mechanisms governing biofilm formation of S. aureus remain not fully elucidated. This study aimed to investigate the function of the S. aureus lineage-specific two-component system, desKR, in biofilm regulation and pathogenicity. Methods: Bioinformatic analysis was conducted to assess the prevalence of desKR across various S. aureus lineages and to examine its structural features. The impact of desKR on S. aureus pathogenicity was evaluated using in vivo mouse models, including skin abscess, bloodstream infection, and nasal colonization models. Crystal violet staining and confocal laser scanning microscopy were utilized to examine the impact of desKR on S. aureus biofilm formation. Mechanistic insights into desKR-mediated biofilm regulation were investigated by quantifying polysaccharide intercellular adhesin (PIA) production, extracellular DNA (eDNA) release, autolysis assays, and RT-qPCR. Results: The prevalence of desKR varied among different S. aureus lineages, with notably low carriage rates in ST398 and ST59 lineages. Deletion of desKR in NCTC8325 strain resulted in decreased susceptibility to β-lactam and glycopeptide antibiotics. Although desKR did not significantly affect acute pathogenicity, the ΔdesKR mutant exhibited significantly reduced nasal colonization and biofilm-forming ability. Overexpression of desKR in naturally desKR-lacking strains (ST398 and ST59) enhanced biofilm formation, suggesting a lineage-independent effect. Phenotypic assays further revealed that the ΔdesKR mutant showed reduced PIA production, decreased eDNA release, and lower autolysis rates. RT-qPCR indicated significant downregulation of icaA, icaD, icaB, and icaC genes, along with upregulation of icaR, whereas autolysis-related genes remained unchanged. Conclusion: The desKR two-component system positively regulates S. aureus biofilm formation in a lineage-independent manner, primarily by modulating PIA synthesis via the ica operon. These findings provide new insights into the molecular mechanisms of biofilm formation in S. aureus and highlight desKR as a potential target for therapeutic strategies aimed at combating biofilm-associated infections. [ABSTRACT FROM AUTHOR]

Abstract Severe cutaneous injuries may not heal spontaneously and may necessitate the use of supplementary therapeutic methods. Electrospun nanofibers possess high porosity and specific surface area, which provide the necessary microenvironment for wound healing. Here in, the nanofibers of Soluplus-soy protein isolate (Sol-SPI) containing mupirocin (Mp) were fabricated via electrospinning for wound treatment. The fabricated nanofibers exhibited water absorption capacities of about 300.83 ± 29.72% and water vapor permeability values of about 821.8 ± 49.12 g/m2 day. The Sol/SPI/Mp nanofibers showed an in vitro degradability of 33.73 ± 3.55% after 5 days. The ultimate tensile strength, elastic modulus, and elongation of the Sol/SPI/Mp nanofibers were measured as 3.61 ± 0.29 MPa, 39.15 ± 5.08 MPa, and 59.11 ± 1.94%, respectively. Additionally, 85.90 ± 6.02% of Mp loaded in the nanofibers was released in 5 days in vitro, and by applying the Mp-loaded nanofibers, 93.06 ± 5.40% and 90.40 ± 5.66% of S. aureus and E. coli bacteria were killed, respectively. Human keratinocyte cells (HaCat) demonstrated notable biocompatibility with the prepared nanofibers. Furthermore, compare to other groups, Sol-SPI-Mp nanofibers caused the fastest re-epithelialization and wound healing in a rat model. The findings of this study present a novel nanofiber-based wound dressing that accelerates the healing of severe skin wounds with the risk of infection.

ImportanceUniversal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.ObjectiveTo compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.Design, setting, and participantsTwo-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included.InterventionUniversal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).Main outcomes and measuresICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%.ResultsAmong the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P

Abstract Background Nasal carriage of Staphylococcus aureus is a risk factor for surgical site infections (SSI) in orthopaedic surgery. The efficacy of decolonisation for S. aureus on reducing the risk of SSI is uncertain in this speciality. The objective was to evaluate the impact of a nasal screening strategy of S. aureus and targeted decolonisation on the risk of S. aureus SSI. Methods A retrospective pre-post and here-elsewhere study was conducted between January 2014 and June 2020 in 2 adult orthopaedic surgical sites (North and South) of a French university hospital. Decolonisation with Mupirocin and Chlorhexidine was conducted in S. aureus carriers starting February 2017 in the South site (intervention group). Scheduled surgical procedures for hip, knee arthroplasties, and osteosyntheses were included and monitored for one year. The rates of S. aureus SSI in the intervention group were compared to a historical control group (South site) and a North control group. The risk factors for S. aureus SSI were analysed by logistic regression. Results A total of 5,348 surgical procedures was included, 100 SSI of which 30 monomicrobial S. aureus SSI were identified. The preoperative screening result was available for 60% (1,382/2,305) of the intervention group patients. Among these screenings, 25.3% (349/1,382) were positive for S. aureus and the efficacy of the decolonisation was 91.6% (98/107). The rate of S. aureus SSI in the intervention group (0.3%, 7/2,305) was not significantly different from the historical control group (0.5%, 9/1926) but differed significantly from the North control group (1.3%, 14/1,117). After adjustment, the risk factors of S. aureus SSI occurrence were the body mass index (ORaper unit, 1.05; 95%CI, 1.0-1.1), the Charlson comorbidity index (ORaper point, 1.34; 95%CI, 1.0–1.8) and operative time (ORaper minute, 1.01; 95%CI, 1.00–1.02). Having benefited from S. aureus screening/decolonisation was a protective factor (ORa, 0.24; 95%CI, 0.08–0.73). Conclusions Despite the low number of SSI, nasal screening and targeted decolonisation of S. aureus were associated with a reduction in S. aureus SSI.

This study was directed to prepare poly (lactic acid) curcumin (Cur)-based nanofibers using the electrospinning method and their evaluation potentially in the presence of titanium dioxide (TiO2) nanoparticles as bioactive wound dressings. The interactions between components, crystallinity nature, and presence of Cur-TiO2 in the prepared nanofibers were demonstrated by Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. Furthermore, scanning electron microscopy images revealed that the existence of Cur-TiO2 in the system caused a decrease in the nanofiber diameters from 264 ± 29 to 210 ± 18 nm, and the significant influence of TiO2 on the hydrophilicity of nanofibers was proved by the water contact angle test. Based on the cytotoxicity studies, TiO2-containing nanofibers were biocompatible and did not reduce the viability of the cultured fibroblast cells. Moreover, it was found that the cell proliferation and level of cell adhesion increased in the presence of Cur-TiO2, and the highest amount of cell growth occurred on scaffolds containing TiO2, according to fluorescent staining. Finally, the antibacterial activities of the samples against Gram-negative and Gram-positive bacteria, named Escherichia coli and Staphylococcus aureus, respectively, were analyzed, which confirmed that the addition of Cur-TiO2 caused bacterial resistance, resulting in their desired potential for being employed in wound dressing applications. [ABSTRACT FROM AUTHOR]

The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges, and the timing and mechanisms of several key transformations remain elusive. Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA‐B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid side chain required for biological activity. Herein, we show that the mini‐module MmpE performs a rare online (ACP‐substrate) epoxidation and is integrated (‘in‐cis’) into the polyketide synthase via a docking domain. A linear polyketide fragment with six asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0 and a previously unannotated ACP (MmpE_ACP). MmpE_ACP‐bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA‐B. [ABSTRACT FROM AUTHOR]

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties. The chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here, we studied the antimicrobial activity of two synthetic PPAP-derivatives, the water-insoluble PPAP23 and the water-soluble sodium salt PPAP53. In vitro, both compounds exhibited good activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar effect was also seen with serum albumin. In silico docking studies with PPAP53 revealed that it binds to the F1 pocket of human serum albumin with a binding energy of −7.5 kcal/mol. In an infection model of septic arthritis, PPAP23 decreased the formation of abscesses and S. aureus load in kidneys; in a mouse skin abscess model, topical treatment with PPAP53 reduced S. aureus counts. Both PPAPs were active against anaerobic Gram-positive gut bacteria such as neurotransmitter-producing Clostridium, Enterococcus or Ruminococcus species. Based on these results, we foresee possible applications in the decolonization of pathogens. [ABSTRACT FROM AUTHOR]

Biofilms, particularly those formed by multiple bacterial species, pose significant economic and environmental challenges, especially in the context of medical implants. Addressing the urgent need for effective treatment strategies that do not exacerbate drug resistance, we developed a novel nanoformulation, Ce6&PMb@BPN, based on black phosphorus nanosheets (BPN) for targeted treatment of mixed-species biofilms formed by Acinetobacter baumannii (A. baumannii) and methicillin-resistant Staphylococcus aureus (MRSA).The formulation leverages polymyxin B (PMb) for bacterial targeting and chlorin e6 (Ce6) for photodynamic action. Upon near-infrared (NIR) irradiation, Ce6&PMb@BPN efficiently eliminates biofilms by combining chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), reducing biofilm biomass significantly within 30 min. In vivo studies on mice infected with mixed-species biofilm-coated catheters demonstrated the formulation's potent antibacterial and biofilm ablation effects. Moreover, comprehensive biosafety evaluations confirmed the excellent biocompatibility of Ce6&PMb@BPN. Taken together, this intelligently designed nanoformulation holds potential for effectively treating biofilm-associated infections, addressing the urgent need for strategies to combat antibiotic-resistant biofilms, particularly mixed-species biofilm, in medical settings. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is one of the most serious biomedical problems that require new agents to combat bacterial pathogens. Potassium aluminium sulphate (alum) has recently drawn the attention of the scientific community as an efficient, safe and eco-friendly inorganic compound with antimicrobial activity. Methods: Ten samples of bacteria, five types of Eschericha coli (E. coli) and five types of S. aureus were isolated from patients. Eschericha coli isolated from urine sample by sterile container. Staphylococcus aureus (S. aureus) isolated from wound samples by a cotton swab. The samples were cultured on the following media (Mannitol salt agar, eosin methylene blue agar, and blood agar). Well diffusion method used to evaluate the antimicrobial activity. Alum aqueous solution with two concentrations (1% and 2%) was determined as well as amoxicillin, gentamicin, and ceftriaxone. Results: E. coli is sensitive by 50%for both concentrations of alum (1%, 2%), S. aureus is 100% resistant to a concentration of 1% of alum and 50% resistant to a concentration of 2% of alum. Combination of amoxicillin with alum for each concentration (1% and 2%) has no significant effect on the activity of amoxicillin for both E. coli and S. aureus (p= 97 and p= 0.62) respectively. Combination of ceftriaxone with alum for each concentration (1% and 2%) has no significant effect. The combination of gentamicin with alum for each concentration in E. coli has no significant effect. But for S. aureus the mean of gentamicin sensitivity was 39.50± 3.87, the mean is decreased after combination with 1% alum 41.50± 4.35 and 2% alum 40± 5.83 with significant statically differences (p= 0.02). Conclusions: The white alum effect is dose response, and greater concentration will lead to enhanced decrease on bacterial growth. This study suggests more than 1% and 2% concentrations of white alum could be used as antimicrobial agent. The effect of 1% and 2% alum combined with ceftriaxone and amoxicillin shoed no significant differences (p> 0.05). [ABSTRACT FROM AUTHOR]

Combination treatment enhances efficacy, minimizes side effects, and improves convenience for patients with diverse treatment schedules. This compilation focuses on the simultaneous estimation of Miconazole nitrate (MNE), Mupirocin (MRN), and Mometasone furoate (MMT) using HPLC and HPTLC in an ointment which is wisely used combination for treatment of skin disorders. The optimized isocratic HPLC method consists of a C18 column, 0.02% triethylamine: methanol (15:85; % v/v), at a flow rate of 0.9 mL/min. The retention times were found to be 4.716 ± 0.082 min for MNE, 13.716 ± 0.188 min for MRN, and 2.241 ± 0.034 min for MMT using the developed method. The method was validated indetail and the quantification range found 20–180 µg/mL for both MNE and MRN and 1–9 µg/mL for MMT. In an alternative HPTLC method, toluene, ethyl acetate, and ethanol (10:3:2; v/v/v) were used as mobile phase on silica gel 60F254-coated aluminum sheets, with scanning at 240 nm. The MNE, MRN and MMT drugs spot eluted at Rf values of 0.65, 0.36, and 0.80, respectively. In-depth validation was performed and assessed statistically, including, specificity, precision, accuracy, reproducibility, and accuracy. The HPTLC method found linear in ranges of 1200–5200 ng/band for MNE and MRN, and 60–260 ng/band for MMT. Consequently, these developed chromatographic methods assessed according to green analytical principle and found sustainable. The developed methods can be effectively applied for the quantitative analysis of commercially available dosage forms. [ABSTRACT FROM AUTHOR]

This study provides a comparative analysis of 243 Methicillin-resistant Staphylococcus aureus (MRSA) isolated strains from Greece and Romania, focusing on their epidemiology and antibiotic resistance patterns. Laboratory procedures included phenotypic and automated identification methods, susceptibility testing, DNA isolation, and PCR for detecting antibiotic resistance genes (MecA, SCCmec). Our study results show significant regional differences. In both regions, males have higher MRSA infection rates than females, but the percentages vary. Greece has a higher incidence of MRSA in younger age groups compared to Romania. The majority of MRSA infections occur in inpatient settings in both countries, highlighting the necessity for enhanced infection control measures. Antibiotic resistance profiles reveal higher resistance to several antibiotics in Greece compared to Romania. A molecular analysis shows a widespread distribution of antibiotic resistance genes among MRSA isolates in Greece. These results highlight the necessity for accomplished preventive strategies and optimized treatment protocols. [ABSTRACT FROM AUTHOR]

In response to the escalating global threat of antimicrobial resistance, our laboratory has established a phagemid packaging system for the generation of CRISPR-Cas13a-antimicrobial capsids targeting methicillin-resistant Staphylococcus aureus (MRSA). However, a significant challenge arose during the packaging process: the unintentional production of wild-type phages alongside the antimicrobial capsids. To address this issue, the phagemid packaging system was optimized by strategically incorporated silent mutations. This approach effectively minimized contamination risks without compromising packaging efficiency. The study identified the indispensable role of phage packaging genes, particularly terL-terS, in efficient phagemid packaging. Additionally, the elimination of homologous sequences between the phagemid and wild-type phage genome was crucial in preventing wild-type phage contamination. The optimized phagemid-LSAB(mosaic) demonstrated sequence-specific killing, efficiently eliminating MRSA strains carrying target antibiotic-resistant genes. While acknowledging the need for further exploration across bacterial species and in vivo validation, this refined phagemid packaging system offers a valuable advancement in the development of CRISPR-Cas13a-based antimicrobials, shedding light on potential solutions in the ongoing battle against bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Nasal carriage of Staphylococcus aureus is a risk factor for surgical site infections (SSI) in orthopaedic surgery. The efficacy of decolonisation for S. aureus on reducing the risk of SSI is uncertain in this speciality. The objective was to evaluate the impact of a nasal screening strategy of S. aureus and targeted decolonisation on the risk of S. aureus SSI. Methods: A retrospective pre-post and here-elsewhere study was conducted between January 2014 and June 2020 in 2 adult orthopaedic surgical sites (North and South) of a French university hospital. Decolonisation with Mupirocin and Chlorhexidine was conducted in S. aureus carriers starting February 2017 in the South site (intervention group). Scheduled surgical procedures for hip, knee arthroplasties, and osteosyntheses were included and monitored for one year. The rates of S. aureus SSI in the intervention group were compared to a historical control group (South site) and a North control group. The risk factors for S. aureus SSI were analysed by logistic regression. Results: A total of 5,348 surgical procedures was included, 100 SSI of which 30 monomicrobial S. aureus SSI were identified. The preoperative screening result was available for 60% (1,382/2,305) of the intervention group patients. Among these screenings, 25.3% (349/1,382) were positive for S. aureus and the efficacy of the decolonisation was 91.6% (98/107). The rate of S. aureus SSI in the intervention group (0.3%, 7/2,305) was not significantly different from the historical control group (0.5%, 9/1926) but differed significantly from the North control group (1.3%, 14/1,117). After adjustment, the risk factors of S. aureus SSI occurrence were the body mass index (ORaper unit, 1.05; 95%CI, 1.0-1.1), the Charlson comorbidity index (ORaper point, 1.34; 95%CI, 1.0–1.8) and operative time (ORaper minute, 1.01; 95%CI, 1.00–1.02). Having benefited from S. aureus screening/decolonisation was a protective factor (ORa, 0.24; 95%CI, 0.08–0.73). Conclusions: Despite the low number of SSI, nasal screening and targeted decolonisation of S. aureus were associated with a reduction in S. aureus SSI. [ABSTRACT FROM AUTHOR]

A 35-year-old intramural male athlete presented to the athletic training staff with a 4.5- × 2.2-cm itchy, painful, swollen, and infected insidious skin lesion on his right lateral malleolus due to an underlying dermatologic deficiency. Suspecting infection, the patient was referred to his nurse practitioner and was diagnosed with atopic dermatitis caused by a ceramide deficiency. He was placed on cefalexin and mupirocin 2% ointment but returned due to the lesion increasing to 8.5 × 6 cm, although the infection seemed controlled. He was instructed to use Ceravé topical cream, clobetasol propionate 5%, and to consume foods rich in healthy oils (omega-3 fatty acids, olive oil). Unmitigated, this lesion could have resulted in severe infection and tissue damage. Atopic dermatitis is relatively common in the general population, but its appearance in healthy athletes highlights that athletic trainers need to be well versed in not just apparent causes of skin ailments (ie, infection) but also root causes. [ABSTRACT FROM AUTHOR]

Background: Infections caused by multidrug-resistant organisms (MDROs) have been increasingly reported from healthcare facilities. The spread of MDROs in hospitals further increases the financial burden on healthcare facility due to prolonged hospital stays and the need for more expensive investigations and treatment. Methicillin Resistant Staphylococcus aureus (MRSA) is known to be widely distributed in the healthcare facilities and accounts for a substantial proportion of the infectious disease burden. Hence, active surveillance for MRSA is carried out to identify colonized patients or Healthcare workers (HCWs) in a facility. This prospective study was conducted to study and compare the carriage of MRSA among doctors, nurses, General Duty Attendants (GDA) and Houseman/ House woman (HM/HW) working in cardiac unit of a tertiary care hospital. Screening was done by collecting swabs from hands and anterior nares. These specimens were processed by standard procedures for the isolation of Staphylococcus aureus and resistance to methicillin was determined using cefoxitin, 30µg disks as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The carriage rate of MRSA was found to be highest among HM/HW (13%) followed by nurses (8%) and GDA (7%). Out of 11 doctors screened, none was found to carry MRSA. A higher percentage carriage in HM/HW can probably be accounted to their close and prolonged contact with infected patients and involvement in activities like emptying urinary bags, floor mopping and other activities of environmental cleaning. Management of MRSA carriers include applying stringent hand hygiene, contact precautions and core strategies including isolating and cohorting patients, increased environmental cleaning, dedicated patient equipment and decolonization. Active surveillance including screening of HCWs can help in decreased risk of spread to their close contacts and further reduction of MRSA prevalence among patients. [ABSTRACT FROM AUTHOR]

Pseudomonas bacteria are renowned for their remarkable capacity to synthesize antibiotics, namely mupirocin, gluconic acid, pyrrolnitrin, and 2,4-diacetylphloroglucinol (DAPG). While these substances are extensively employed in agricultural biotechnology to safeguard plants against harmful bacteria and fungi, their potential for human medicine and healthcare remains highly promising for common science. However, the challenge of obtaining stable producers that yield higher quantities of these antibiotics continues to be a pertinent concern in modern biotechnology. Although the interest in antibiotics of Pseudomonas bacteria has persisted over the past century, many uncertainties still surround the regulation of the biosynthetic pathways of these compounds. Thus, the present review comprehensively studies the genetic organization and regulation of the biosynthesis of these antibiotics and provides a comprehensive summary of the genetic organization of antibiotic biosynthesis pathways in pseudomonas strains, appealing to both molecular biologists and biotechnologists. In addition, attention is also paid to the application of antibiotics in plant protection. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance occurs mostly through the ineffective and unauthorized use of antibiotics in both the environment and health care. Biofilms are a new target in the search for new antibacterial agents. Here, the sol‐gel method is used to produce zinc oxide quantum dots (ZnO‐QDs). The ZnO‐QDs show yellow emission at 526 nm under 360 nm excitation. After that, the ability of ZnO‐QDs as an antibacterial and antibiofilm agent against methicillin‐resistant Staphylococcus aureus (MRSA) is examined. The 100 samples are collected from patients with hospital‐acquired infections between December 2020 and October 2021 from Imamen Kadhmiyan Teaching Hospital in Baghdad (Iraq). Out of these 100 samples, 63 are S. aureus and 20 out of 63 are MRSA. The minimum inhibitory concentration assay demonstrates the antibacterial activity of ZnO‐QDs on MRSA strains. Also, results show that 80, 5, and 15% of isolated MRSA strains produce strong, moderate, and weak or very weak biofilm, respectively. The effect of ZnO‐QDs on strong and moderate biofilms reveal that QDs could also inhibit and destroy biofilm produced by MRSA. In addition, the antibiofilm effect of ZnO‐QDs is greater than their antibacterial effect. Generally, this work offers new insights into the development of antibacterial and antibiofilm nanomaterials. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)–signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition. Editor's summary: Epidermal growth factor receptor inhibitors (EGFRis) are used to treat several common cancers, but EGFRi use is frequently complicated by a skin rash that shows limited response to current treatments. Here, You et al. conducted a transcriptomic analysis of the skin of rats exposed to an EGFRi to uncover early changes preceding rash development, finding early activation of keratinocytes that led to activation of the JAK-STAT pathway and recruitment of inflammatory cells. Topical JAK inhibition ameliorated rash in EGFRi-treated rodents without effects on antitumor efficacy, and a pilot clinical study of topical JAK inhibition in 11 patients with EGFRi-induced rash showed improvement in rash severity, suggesting topical JAK inhibition as a strategy to manage this condition in patients. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

ZnO nanorod nonwoven fabrics (ZNRN) were developed through hydrothermal synthesis to facilitate the prevention of the transmission of respiratory pathogens. The superhydrophobicity and antibacterial properties of ZNRN were improved through the response surface methodology. The synthesized material exhibited significant water repellency, indicated by a water contact angle of 163.9°, and thus demonstrated antibacterial rates of 91.8% for Escherichia coli (E. coli) and 79.75% for Staphylococcus aureus (S. aureus). This indicated that E. coli with thinner peptidoglycan may be more easily killed than S. aureus. This study identified significant effects of synthesis conditions on the antibacterial effectiveness, with comprehensive multivariate analyses elucidating the underlying correlations. In addition, the ZnO nanorod structure of ZNRN was characterized through SEM and XRD analyses. It endows the properties of superhydrophobicity (thus preventing bacteria from adhering to the ZNRN surface) and antibacterial capacity (thus damaging cells through the puncturing of these nanorods). Consequently, the alignment of two such features is desired to help support the development of personal protective equipment, which assists in avoiding the spread of respiratory infections. [ABSTRACT FROM AUTHOR]

The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole–4,9–dione compounds (5a–e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a–e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole–4,9–dione skeleton and substituent effect, 5a–e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b–e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a–e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future. [ABSTRACT FROM AUTHOR]

Electrospinning has garnered much attention for skin renewal, emphasizing skin's pivotal role as a primary protective layer and the susceptibility to loss caused by burns. The research aimed to develop a multipurpose wound dressing that safeguard injuries and facilitates the renewal of dermal tissues. Two-layer nanofibers were prepared using polyvinyl alcohol–chitosan–gelatin/polyacrylonitrile (PVA–CS–Gel/PAN), containing mupirocin (Mu 3% w/w) in underlying layer and silver nanoparticles (AgNps) in the upper layer with varying concentrations. AgNps were synthesized from Capsella bursa-pastoris extract by the green method and characterized using XRD, SEM, FTIR, and UV techniques. Then, PVA–CS–Gel/PAN solutions with AgNps and Mu were electrospun into multilayer dressings. The effectiveness of the nanofibers was evaluated through in vitro and in vivo tests. The study examined the nanofibers containing spherical AgNps with an average diameter of 72.57 nm and a negative surface charge (− 12 mv). They had uniform and smooth surfaces with a diameter range of 476.31 to 926.04 nm. According to swelling and contact angle results, hydrophilicity of samples had a direct relation with water absorption. Controlled drug release within 72 h followed Higuchi or first-order profiles. MTT and antibacterial analyses indicated that optimized nanofibers (Mu/1% AgNps) had suitable biocompatibility and synergistic potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. Additionally, an in vivo test on rats with second-degree burns after 28 days demonstrated a 98.97% improvement in revival, outperforming its commercial counterparts. Consequently, the results position the designed composite nanofiber as a promising candidate for wound healing applications, aiding in enhancing skin regeneration. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus can colonize and infect a variety of animal species. In dairy herds, it is one of the leading causes of mastitis cases. The objective of this study was to characterize the S. aureus isolates recovered from nasal swabs of 249 healthy cows and 21 breeders of 21 dairy farms located in two provinces of Algeria (Tizi Ouzou and Bouira). Methods: The detection of enterotoxin genes was investigated by multiplex PCRs. Resistance of recovered isolates to 8 antimicrobial agents was determined by disc-diffusion method. The slime production and biofilm formation of S. aureus isolates were assessed using congo-red agar (CRA) and microtiter-plate assay. Molecular characterization of selected isolates was carried out by spa-typing and Multi-Locus-Sequence-Typing (MLST). Results: S. aureus was detected in 30/249 (12%) and 6/13 (28.6%) of nasal swabs in cows and breeders, respectively, and a total of 72 isolates were recovered from positive samples (59 isolates from cows and 13 from breeders). Twenty-six of these isolates (36.1%) harbored genes encoding for staphylococcal enterotoxins, including 17/59 (28.8%) isolates from cows and 9/13 (69.2%) from breeders. Moreover, 49.1% and 92.3% of isolates from cows and breeders, respectively, showed penicillin resistance. All isolates were considered as methicillin-susceptible (MSSA). Forty-five (76.3%) of the isolates from cows were slime producers and 52 (88.1%) of them had the ability to form biofilm in microtiter plates. Evidence of a possible zoonotic transmission was observed in two farms, since S. aureus isolates recovered in these farms from cows and breeders belonged to the same clonal lineage (CC15-ST15-t084 or CC30-ST34-t2228). Conclusions: Although healthy cows in this study did not harbor methicillin-resistant S. aureus isolates, the nares of healthy cows could be a reservoir of enterotoxigenic and biofilm producing isolates which could have implications in human and animal health. [ABSTRACT FROM AUTHOR]

Bacterial RNAP needs to form holoenzyme with σ factors to initiate transcription. While Staphylococcus aureus σA controls housekeeping functions, S. aureus σB regulates virulence, biofilm formation, persistence, cell internalization, membrane transport, and antimicrobial resistance. Besides the sequence difference, the spacers between the −35 element and −10 element of σB regulated promoters are shorter than those of σA regulated promoters. Therefore, how σB recognizes and initiates transcription from target promoters can not be inferred from that of the well studied σ. Here, we report the cryo-EM structures of S. aureus RNAP-promoter open complexes comprising σA and σB, respectively. Structural analyses, in combination with biochemical experiments, reveal the structural basis for the promoter specificity of S. aureus transcription. Although the −10 element of σA regulated promoters is recognized by domain σA2 as single-stranded DNA, the −10 element of σB regulated promoters is co-recognized by domains σB2 and σB3 as double-stranded DNA, accounting for the short spacers of σB regulated promoters. S. aureus RNAP is a validated target of antibiotics, and our structures pave the way for rational drug design targeting S. aureus RNAP. Here, Yuan, Liu, and Xu et al. report cryo-EM structures of Staphylococcus aureus RNAP-promoter open complexes, highlighting distinct interactions of σA and σB with their cognate promoters. [ABSTRACT FROM AUTHOR]

Mupirocin is a broad-spectrum antibiotic that acts predominantly against Gram-positive bacteria. It is produced by Pseudomonas fluorescens NCIMB 10586 and has been clinically used to treat primary and secondary skin infections and to eradicate nasal colonisation of methicillin-resistant Staphylococcus aureus strains. Mupirocin inhibits protein synthesis by blocking the active site of isoleucyl-tRNA synthetase (IleRS), which prevents the enzyme from binding isoleucine and ATP for Ile-tRNAIle synthesis. Two types of IleRS are found in bacteria - while IleRS1 is susceptible to mupirocin inhibition, IleRS2 provides resistance to cells. These two types belong to distinct evolutionary clades which likely emerged from an early gene duplication in bacteria. Resistance in IleRS2 is based on the loss of interactions that govern mupirocin binding to IleRS1, such as hydrogen bonding to the carboxylate moiety of mupirocin. IleRS2 enzymes with Ki in the millimolar range have recently been discovered. These hyper-resistant IleRS2 variants surprisingly have a non-canonical version of the catalytic motif, which serves as a signature motif of class I aminoacyl-tRNA synthetases to which IleRS belongs. The non-canonical motif, in which the 1st and 3rd positions are swapped, is key for hyper-resistance and can be accommodated without abolishing enzyme activity in IleRS2 but not in IleRS1. Clinical use of mupirocin led to the emergence of resistance in S. aureus. Low-level resistance arises by mutations of the housekeeping IleRS1, while high-level resistance develops by the acquisition of the resistant IleRS2 on a plasmid. There is no evidence that hyperresistant variants have been found in clinical isolates. [ABSTRACT FROM AUTHOR]

The treatment of skin and soft tissue infections (SSTIs) can be challenging due to bacterial resistance, particularly from strains like MRSA and biofilm formation. However, combining conventional antibiotics with natural products shows promise in treating SSTIs. The objective of this study is to develop a nanoemulsion-based hydrogel containing Protium spruceanum extract and mupirocin and evaluate its potential for the treatment of SSTIs. The nanoemulsion was obtained by phase inversion and subsequently characterized. The antibacterial activity was evaluated in vitro against S. aureus MRSA, including the synergism of the combination, changes in membrane permeability using flow cytometry, and the anti-biofilm effect. In addition, the irritative potential was evaluated by the HET-CAM assay. The combination exhibited synergistic antibacterial activity against S. aureus and MRSA due to the extract enhancing membrane permeability. The hydrogel demonstrated suitable physicochemical properties, inhibited biofilm formation, and exhibited low irritation. The formulation was nanometric (176.0 ± 1.656 nm) and monodisperse (polydispersity index 0.286 ± 0.011). It exhibited a controlled release profile at 48 h and high encapsulation efficacy (94.29 ± 4.54% for quercitrin and 94.20 ± 5.44% for mupirocin). Therefore, these findings suggest that the hydrogel developed could be a safe and effective option for treating SSTIs. [ABSTRACT FROM AUTHOR]

Nasal mucoadhesive in situ gelling liquid crystalline precursor system (IGFPS) of nystatin was developed for localized treatment of nasal aspergillosis post COVID infection. The stimuli-sensitive sol system comprising of Monoolein (60%w/w), Oleic acid (10%w/w), Dimethyl sulfoxide (15%w/w), Poloxamer 407 (9%w/w), and the drug (2.23%w/w) exhibited a faster sol–gel transformation in situ with good swelling ability. The small angle X-ray scattering study identified the coexistence of Im3m cubic phase with hexagonal closed pack P63/mmc structures. The subzero differential scanning calorimetry studies identified entrapped interphasal water and free water in the gels with confirmation of gelation due to micellization. Mucoadhesive properties of the gel indicate these systems to prolong the residence time at the site of absorption. The gels followed Non-Newtonian flow pattern characteristic of pesudoplastic type. The oscillatory rheology revealed that high complex viscosity and lower tanδ value provided superior adhesiveness and mucoadhesion ability to the gel. The gel exhibited a drug release of 86% at the end of 8h and of Higuchi kinetics with anomalous transport. The IGFPS exhibited better in vitro antifungal activity in comparison to drug solution. The system demonstrated permeation enhancing effect undamaged cilia and no serious histological changes. Post intranasal administration the maximum concentration (11.79 ± 2.31 μg/ml) was realized in 20 min and the curve showed a decline similar to intravenous. The storage stability of the IGFPS was found to be within acceptable limits for stability. Thus, a nasal mucoadhesive in situ gelling fluid liquid crystalline precursor formulation may represent a promising novel alternative for the localized and systemic delivery of nystatin. [ABSTRACT FROM AUTHOR]

Coagulase-negative Staphylococcus (CoNS) species inhibiting Staphylococcus aureus has been described in the skin of atopic dermatitis (AD) patients. This study evaluated whether Staphylococcus spp. from the skin and nares of AD and non-AD children produced antimicrobial substances (AMS). AMS production was screened by an overlay method and tested against NaOH, proteases and 30 indicator strains. Clonality was assessed by pulsed-field gel electrophoresis. Proteinaceous AMS-producers were investigated for autoimmunity by the overlay method and presence of bacteriocin genes by polymerase chain reaction. Two AMS-producers had their genome screened for AMS genes. A methicillin-resistant S. aureus (MRSA) produced proteinaceous AMS that inhibited 51.7% of the staphylococcal indicator strains, and it was active against 60% of the colonies selected from the AD child where it was isolated. On the other hand, 57 (8.8%) CoNS from the nares and skin of AD and non-AD children, most of them S. epidermidis (45.6%), reduced the growth of S. aureus and other CoNS species. Bacteriocin-related genes were detected in the genomes of AMS-producers. AMS production by CoNS inhibited S. aureus and other skin microbiota species from children with AD. Furthermore, an MRSA colonizing a child with AD produced AMS, reinforcing its contribution to dysbiosis and disease severity. [ABSTRACT FROM AUTHOR]