Methicillin-resistant Staphylococcus Aureus Research Articles

The Relative Importance of Cytotoxins Produced by Methicillin-Resistant Staphylococcus aureus Strain USA300 for Causing Human PMN Destruction.

Staphylococcus aureus (S. aureus) is a prominent Gram-positive bacterial pathogen that expresses numerous cytotoxins known to target human polymorphonuclear leukocytes (PMNs or neutrophils). These include leukocidin G/H (LukGH, also known as LukAB), the Panton-Valentine leukocidin (PVL), γ-hemolysin A/B (HlgAB), γ-hemolysin B/C (HlgBC), leukocidin E/D (LukED), α-hemolysin (Hla), and the phenol-soluble modulin-α peptides (PSMα). However, the relative contribution of each of these cytotoxins in causing human PMN lysis is not clear. In this study, we used a library of cytotoxin deletion mutants in the clinically relevant methicillin-resistant S. aureus (MRSA) isolate LAC (strain ST8:USA300) to determine the relative importance of each for causing human PMN lysis upon exposure to extracellular components as well as following phagocytosis. Using flow cytometry to examine plasma membrane permeability and assays quantifying lactose dehydrogenase release, we found that PVL was the dominant extracellular factor causing human PMN lysis produced by USA300. In contrast, LukGH was the most important cytotoxin causing human PMN lysis immediately following phagocytosis with contributions from the other bicomponent leukocidins only observed at later time points. These results not only clarify the relative importance of different USA300 cytotoxins for causing human PMN destruction but also demonstrate how two apparently redundant virulence factors play distinctive roles in promoting S. aureus pathogenesis.

Synthesis, Characterization and Application of Advanced Antimicrobial Electrospun Polymers.

The aim of this work was to synthesize, characterize and apply advanced antimicrobial biocompatible electrospun polymers suitable for medical implants for surgical repairs. Injuries to the musculoskeletal system often necessitate surgical repair, but current treatments can still lead to high failure rates, such as 40% for the repair of rotator cuff tears. Therefore, there is an urgent need for the development of new biocompatible materials that can effectively support the repair of damaged tissues. Additionally, infections acquired during hospitalization, particularly those caused by antibiotic-resistant bacteria, result in more fatalities than AIDS, tuberculosis, and viral hepatitis combined. This underscores the critical necessity for the advancement of antimicrobial implants with specialized coatings capable of combating Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA), two strains notoriously known for their antibiotic resistance. Therefore, we developed an antimicrobial coating incorporating nanoparticle mixtures using the sol-gel process and applied it to electrospun polycaprolactone (PCL) filaments, followed by thorough characterization by using spectroscopic (FTIR, Raman, NMR) microscopic (SEM and SEM-EDX), and tensile test. The results have shown that the integration of electro-spinning technology for yarn production, coupled with surface modification techniques, holds significant potential for creating antimicrobial materials suitable for medical implants for surgical repairs.

Emergence of methicillin-resistant Staphylococcus aureus (MRSA) RdJ clone (CC5-ST105-SCCmecII-t002) in Santa Catarina, Brazil

The emergence of highly successful genetic lineages of methicillin-resistant Staphylococcus aureus (MRSA) poses a challenge in human healthcare due to increased morbidity and mortality rates. The RdJ clone (CC5-ST105-SCCmecII-t002 lineage), previously identified in Rio de Janeiro, Brazil, was linked to bloodstream infections and features a mutation in the aur gene (encoding aureolysin). Additionally, clinical isolates derived from this clone were more effective at evading monocytic immune responses. This study aimed to detect the RdJ clone among clinical MRSA isolated in Santa Catarina (SC) and examine its antimicrobial resistance and phagocytosis evasion capabilities. Our findings revealed the RdJ clone in 20 % of MRSA isolates, all exhibiting multiresistance. RdJ clone isolates from SC did not demonstrate a decreased rate of phagocytosis compared to CC5 non-RdJ isolates. Structural analysis suggests that the aur mutation is unlikely to significantly impact aureolysin activity. Genomic analysis of one isolate unveiled a genetic variant of the RdJ clone, sharing lineage and gene distribution but lacking the aur mutation. This study enhances the understanding of the clinical and epidemiologic risks associated with the RdJ clone and the biological mechanisms underlying its spreading in SC.

Rate of nosocomial MRSA transmission evaluated via contact screening

BackgroundThe prevention of methicillin-resistant S. aureus (MRSA) transmission in the healthcare setting is a priority in Infection Control practices. A cornerstone of this policy is contact tracing of nosocomial contacts after an unexpected MRSA finding. The objective of this retrospective study was to quantify the rates of MRSA transmission in different clinical settings.MethodsThis multi-centre study included MRSA contact screening results from two regional hospitals and one academic hospital. MRSA contact tracing investigations from 2000 until 2019 were reviewed and post-contact screening results were included of index patients with an MRSA-positive culture and their unprotected contacts. Available typing results were used to rule out incidental findings.ResultsOf 27,377 contacts screened after MRSA exposure, 21,488 were Health Care Workers (HCW) and 4816 patients. Post-contact screening was initiated for a total of 774 index cases, the average number of screened contacts per index case was 35.7 (range 1 to 640). MRSA transmission was observed in 0.15% (41) of the contacts, 19 (0.09%) HCW and 22 (0.46%) patients. The number needed to screen to detect one MRSA transmission was 667. The highest risk of MRSA transmission occurred during patient-to-patient contacts, with transmission rates varying from 0.32 to 1.32% among the participating hospitals. No transmissions were detected in HCW (n=2834) in the outpatient setting, and the rate of transmissions among HCW contacts on the wards was 0.13% (19 of 15,874). Among 344 contacts of patients with contact precautions, no transmissions were detected.ConclusionsReconsidering current MRSA contact tracing practices may lead to a more targeted approach with a lower number needed to screen.

Retention of methicillin susceptibility in Staphylococcus aureus using natural adjuvant as an allosteric modifier of penicillin-binding protein 2a

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global public health challenge due to its resistance to conventional antibiotics, primarily mediated by the mutated penicillin-binding protein, PBP2a. This study aims to investigate the potential of phytochemicals derived from medicinal plants in the Indian subcontinent to serve as adjuvants, enhancing the efficacy of methicillin against MRSA through allosteric modification of PBP2a using molecular docking and molecular dynamics (MD) simulation. After comprehensive Absorption, Distribution, Metabolism, and Excretion (ADME) profiling, along with AMES and hepatotoxicity tests, 9 compounds were shortlisted as suitable adjuvant candidates. Among them, nimbolide, quercetin, emodin, daidzein, eriodictyol, luteolin, and apigenin exhibited strong binding affinity to the allosteric site of PBP2a, with docking scores ranging from −8.7 to −7.3 kcal/mol. These phytochemicals facilitated enhanced methicillin binding, as evidenced by improved docking scores ranging from −6.1 to −6.8 kcal/mol, compared to −5.6 kcal/mol for methicillin alone. Molecular dynamics simulations confirmed the stability and favorable conformations of phytochemical-PBP2a complexes. Quercetin and daidzein were identified as the most promising adjuvant candidates, forming stable and energetically favorable complexes with PBP2a. Experimental validation showed that quercetin, at 30 mg/mL, effectively retained methicillin's antibacterial efficacy against MRSA. This study underscores the potential of natural compounds in overcoming antibiotic resistance and suggests that phytochemical-antibiotic synergism could be a viable strategy to combat multidrug-resistant bacterial infections.

Systematic review and meta-analysis on antimicrobial resistance and drug resistance in Saudi Arabia

BackgroundAntimicrobial resistance (AMR) and drug resistance have emerged as major global health concerns, threatening the effectiveness of antimicrobial agents and compromising patient outcomes [21]. The rapid spread of resistant pathogens poses significant challenges to healthcare systems worldwide, leading to increased morbidity, mortality, and healthcare costs [20]. Methods Search StrategyTo find pertinent studies released up until September 2023, a thorough search was done in electronic databases like PubMed, Embase, and Scopus. The search method combined terms linked to Saudi Arabia, drug resistance, and antimicrobial resistance (AMR). The specific search terms and Boolean operators used were tailored to the requirements and functionalities of each database. ResultsThe systematic review includes 25 papers in total, representing various Saudi Arabian healthcare environments and patient groups. The prevalence of AMR varied across different pathogens and antimicrobial agents. The most resistant Enterobacteriaceae were carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum -lactamase-producing Enterobacteriaceae (ESBL), and methicillin-resistant Staphylococcus aureus (MRSA). The full manuscript will report the pooled prevalence rates and 95% CIs for each resistance type. The rates for such bacteria were 38.7%, 26.4%, and 15.2% respectively suggesting an imminent need for improvement in surveillance measures & interventions to reduce the burden of AMR (Antimicrobial Resistance). ConclusionThe prevalence of antibiotic resistance (AMR) is alarmingly high in Saudi Arabia. The aim of this study was to examine the prevalence of AMR across different types of pathogens and antimicrobial agents. A meta-analysis was conducted to quantify the pooled prevalence of each type of resistance across hospitals, environments, and food samples from Saudi Arabian locations. The study identified three types of resistance: carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum -lactamaseproducing Enterobacilli (ESBL), and methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, the study identified several risk factors associated with AMR, including prior antibiotic use, healthcare-associated infections, and prolonged hospital stays.

Unraveling the genetic basis of antibiotic resistance in Staphylococcus aureus: Focus on mecA and PVL Genes

Background Staphylococcus aureus infections, including Methicillin-Resistant S. aureus (MRSA) and Methicillin-Sensitive S. aureus (MSSA), present significant challenges in healthcare due to rising antimicrobial resistance. This study evaluates the genetic basis of antibiotic resistance in S. aureus, focusing on key resistance-associated genes mecA and PVL. Methods A total of 568 clinical specimens were analyzed for the presence of S. aureus. Demographic data were collected to assess age-dependent prevalence. Antimicrobial susceptibility testing was conducted to evaluate resistance patterns. The prevalence of the mecA and PVL genes was determined using molecular techniques. Results S. aureus was identified in 37.9% of cases, with the highest prevalence (60-79 age group). All S. aureus isolates showed 100% resistance to penicillin. Multidrug-resistant (MDR) strains accounted for 84.19% of isolates, with a significant presence of extensively drug-resistant (XDR) strains. The mecA gene was prevalent in 82.79% of MRSA isolates, indicating its strong association with methicillin resistance. Additionally, 41.86% of all S. aureus isolates were positive for the PVL gene, highlighting its widespread distribution. Conclusions The high prevalence of mecA and PVL genes in S. aureus strains underscores the challenges in managing these infections. These findings emphasize the necessity for judicious antibiotic use and enhanced collaborative efforts to combat antimicrobial resistance. Understanding the genetic basis of resistance can inform more effective diagnostic, therapeutic, and preventive strategies, ultimately improving patient outcomes in S. aureus infections.

Bioactive potential of Mentha arvensis L. essential oil

The aim of this study was to evaluate the phytotoxic, genotoxic, cytotoxic and antimicrobial effects of the Mentha arvensis L. essential oil (EO). The biological activity of M. arvensis EO depended on the analyzed variable and the tested oil concentration. Higher concentrations of EO (20 and 30 µg mL−1) showed a moderate inhibitory effect on the germination and growth of seedlings of tested weed species (Bellis perennis, Cyanus segetum, Daucus carota, Leucanthemum vulgare, Matricaria chamomilla, Nepeta cataria, Taraxacum officinale, Trifolium repens and Verbena × hybrida). The results obtained also indicate that the EO of M. arvensis has some genotoxic, cytotoxic and proliferative potential in both plant and human in vitro systems. Similar results were obtained for antimicrobial activity against eight bacteria, including multidrug-resistant (MDR) strains [Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, extended-spectrum beta-lactamase-producing (ESBL) E. coli, Pseudomonas aeruginosa and Salmonella enterica subsp. enterica serovar Enteritidis], with the effect on multidrug-resistant bacterial strains. Research indicates that the EO of M. arvensis shows phytotoxic, genotoxic, cytotoxic and antimicrobial effects, as well as its potential application as a herbicide and against various human diseases.

BOPHY Derivatives as Phototherapeutic Agents for the Photodynamic Inactivation of Microorganisms

AbstractThe improvement of photodynamic inactivation (PDI) significantly depends on the development of new families of photosensitizers (PSs). In this sense, three BOPHY derivatives (BP, BP‐Br and BP‐I) were synthetized, studied, and compared to assess their antimicrobial photodynamic properties. BP is an interesting fluorescent probe for cell imaging, while the halogenated analogs (BP‐Br and BP‐I) are excellent oxygen photosensitizing agents. BP compound presented a fluorescence quantum yield close unity and showed no reactive oxygen species (ROS) production. In contrast, BP‐I did not show emission properties but exhibited a high production of ROS through both photodynamic mechanisms, generating singlet oxygen (type II) and superoxide radical anion (type I) under aerobic light irradiation. BP‐Br presented an adequate balance between ROS production and emission properties. The photokilling action and the binding to bacterial cells of these macrocycles were evaluated in vitro against methicillin‐resistant Staphylococcus aureus (MRSA) and Escherichia coli bacteria. Our results demonstrated that the halogenated BOPHY derivatives were effective PSs in inactivating MRSA using shorter irradiation periods. In addition, the antimicrobial action sensitized by these BOPHYs was potentiated by adding KI. The combination of halogenated BOPHY and KI led to a complete elimination of both Gram‐positive and Gram‐negative bacteria. Hence, BP‐Br and BP‐I prove to be potent broad‐spectrum antimicrobial PSs. To the best of our knowledge, this is the first time that BOPHY derivatives have been applied to photokill pathogenic microorganisms.

Methicillin-Resistant Staphylococcus aureus (MRSA) in Different Food Groups and Drinking Water.

Methicillin-resistant Staphylococcus aureus (MRSA) has been included by the World Health Organization in its list of "priority pathogens" because of its widespread prevalence and the severity of the infections it causes. The role of food in infections caused by MRSA is unknown, although strains of this microorganism have been detected in various items for human consumption. In order to gain an overview of any possible role of food in MRSA infections, a review was undertaken of studies published between January 2001 and February 2024 relating to MRSA. These comprised research that focused on fish and shellfish, eggs and egg products, foods of vegetable origin, other foodstuffs (e.g., honey or edible insects), and drinking water. In most of these investigations, no prior enrichment was carried out when isolating strains. Three principal methods were used to confirm the presence of MRSA, namely amplification of the mecA gene by PCR, amplification of the mecA and the mecC genes by PCR, and disc diffusion techniques testing susceptibility to cefoxitin (30 μg) and oxacillin (1 μg). The great diversity of methods used for the determination of MRSA in foods and water makes comparison between these research works difficult. The prevalence of MRSA varied according to the food type considered, ranging between 0.0% and 100% (average 11.7 ± 20.3%) for fish and shellfish samples, between 0.0% and 11.0% (average 1.2 ± 3.5%) for egg and egg products, between 0.0% and 20.8% (average 2.5 ± 6.8%) for foods of vegetable origin, between 0.6% and 29.5% (average 28.2 ± 30.3%) for other foodstuffs, and between 0.0% and 36.7% (average 17.0 ± 14.0%) for drinking water.

Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides.

A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a-f and 6a-f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a-h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a-d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a-f and 6a-f and 1,2,3-triazole derivatives 7a-h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a-f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 µM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.

Screening canine sources for novel antimicrobials reveals the circular broad-spectrum bacteriocin, caledonicin, produced by Staphylococcus caledonicus.

Antimicrobial-resistant pathogens present an ongoing threat to human and animal health, with deaths linked to antimicrobial resistance (AMR) predicted to increase annually. While the misuse and overuse of antibiotics in humans undoubtedly contribute to this escalation, antibiotic use in the veterinary field, including companion animals, also plays a contributing role. Pet owners' desire to improve the quality of life of their pets is likely to support antibiotic use in this field. Consequently, there is a need for antibiotic alternatives to treat bacterial infections. This study set out to screen for antimicrobial peptides known as bacteriocins from bacterial isolates of aerobic/microaerophilic environments of canine sources and determine their potential as antibiotic alternatives against clinically relevant pathogens. Following a laboratory-based protocol, 22 bacterial isolates were subjected to whole-genome sequencing (WGS), and a total of 14 putative novel bacteriocins were identified from both class I and II bacteriocin classes. One particular bacteriocin, herein named caledonicin, was identified via in silico analysis from a Staphylococcus caledonicus strain and partially purified for further in vitro evaluation. Caledonicin is a 64-amino acid (IAANLGVSSGTAYS MANALNNISNVATA LTIIGTFTGVGTIGSGIA ATILAILKKKGVAAAAAF) novel circular bacteriocin most closely related to enterocin_NKR-5-3B based on core peptide alignment (39.1%), with a molecular weight of 6077.1 Da. Caledonicin exhibits a broad-spectrum of activity against a range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP), and Listeria monocytogenes; and the gut-related bacterium associated with Crohn's disease, Mediterraneibacter gnavus ATCC 29149 (previously Ruminococcus gnavus ATCC 29149). This represents the first bacteriocin screening study involving bacteria from canine sources and confirms this is a rich environment for bacteriocin-producing strains. This study also identifies and characterises the first novel bacteriocin from the staphylococcal species, Staphylococcus caledonicus.

Bi2Se3/PAAS Hydrogels with Photothermal and Antioxidant Properties for Bacterial Infection Wound Therapy by Improving Vascular Function and Regulating Glycolipid Metabolism.

Skin is the largest organ in the human body, and it is also the most important natural barrier. However, some accidents can cause skin damage. Bacterial infections and inflammatory reactions can hinder wound healing. Therefore, eliminating bacterial infections and regulating oxidative stress are essential. The use of antibiotics is no longer sufficient because of bacterial resistance. The development of new nanomaterials provides another way of thinking about bacterial drug resistance. In this study, bismuth selenide is modified with polyethylpyrrolidone to obtain a 2D nanomaterial with negligible toxicity and then added to a sodium polyacrylate hydrogel, which is nontoxic and has strong tissue adhesion and a weak antibacterial effect. To further enhance antibacterial performance, photothermal therapy is a good strategy. Under near-infrared light, Bi2Se3/PAAS shows a strong bactericidal effect. Bi2Se3/PAAS hydrogels also have certain antioxidant effects and are used to remove excess free radicals from wound infections. The effective therapeutic effect of Bi2Se3/PAAS/NIR on methicillin-resistant Staphylococcus aureus (MRSA) infection is further verified in animal models. Transcriptome analysis reveals that the Bi2Se3/PAAS hydrogel improves the function of vascular endothelial cells, regulates glucose and lipid metabolism, and promotes the healing of infected wounds.

Tracking Vancomycin MIC Creep: A Five Year Analysis

Methicillin resistant Staphylococcus aureus (MRSA) is a known human pathogen capable of causing community and hospital acquired infections worldwide. Treatment options available for MRSA infections are limited, with vancomycin being one of the most common drugs used. It is described in the literature that vancomycin can be ineffective against MRSA isolates with MIC values between 1-2 mg/litre. This slow and steady shift of vancomycin MIC values towards higher side over a period of time is known as “MIC creep”. The present retrospective study was carried out over five year period from January 2019 to June 2023. Staphylococcus aureus isolates from all clinical samples isolated during study period were included in the study. MIC50, MIC90, geometric mean MIC values were determined and analysed using Microsoft Excel. In the present study, the prevalence of MRSA was high (79.6%) in pus and tissue samples followed by blood sample (9.7%). Most of the MRSA isolates (55.80%) in present study exhibited vancomycin MIC of 1 µg/ml, there is no increasing trend of MIC values over a five year period. MIC creep is a slow and steady process which is multifactorial in origin. Regular monitoring of vancomycin MIC trend is advisable as vancomycin is the first-line treatment for culture proven severe infection with MRSA.

Genomic Characterization of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Implicated in Bloodstream Infections, KwaZulu-Natal, South Africa: A Pilot Study.

Staphylococcus aureus is an opportunistic pathogen and a leading cause of bloodstream infections, with its capacity to acquire antibiotic resistance genes posing significant treatment challenges. This pilot study characterizes the genomic profiles of S. aureus isolates from patients with bloodstream infections in KwaZulu-Natal, South Africa, to gain insights into their resistance mechanisms, virulence factors, and clonal and phylogenetic relationships. Six multidrug-resistant (MDR) S. aureus isolates, comprising three methicillin-resistant S. aureus (MRSA) and three methicillin-susceptible S. aureus (MSSA), underwent whole genome sequencing and bioinformatics analysis. These isolates carried a range of resistance genes, including blaZ, aac(6')-aph(2″), ant(9)-Ia, ant(6)-Ia, and fosB. The mecA gene, which confers methicillin resistance, was detected only in MRSA strains. The isolates exhibited six distinct spa types (t9475, t355, t045, t1265, t1257, and t7888) and varied in virulence gene profiles. Panton-Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types, IVd(2B) and I(1B), were identified, and the isolates were classified into four multilocus sequence types (MLSTs), with ST5 (n = 3) being the most common. These sequence types clustered into two clonal complexes, CC5 and CC8. Notably, two MRSA clones were identified: ST5-CC5-t045-SCCmec_I(1B) and the human-associated endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). Phylogenomic analysis revealed clustering by MLST, indicating strong genetic relationships within clonal complexes. These findings highlight the value of genomic surveillance in guiding targeted interventions to reduce treatment failures and mortality.

Excellent antibacterial and anti-inflammatory efficacy of amoxicillin by AgNPs and their conjugates synthesized using Micromeria biflora crude flavonoid extracts

Antibacterial resistance is considered to be one of the major causes for mortality in coming years. In recent years green nanotechnology played a key role in addressing this problem. Biocompatible metal nanoparticles have gained popularity owing to their excellent therapeutic effects and minimal side effects. MethodWe report the synthesis of AgNPs and their amoxicillin conjugates (Ag-amoxi) using Micromeria biflora crude flavonoid extracts. The physicochemical properties of the synthesized NPs and Ag-amoxi conjugates were systematically evaluated using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and X-ray diffraction (XRD) analysis, Fourier transform infrared (FTIR), and UV–visible (UV–Vis) spectroscopic techniques. ResultsThe average sizes of AgNPs and Ag-amoxi conjugates were 45 and 62 nm, respectively. We have also explored the antibacterial, antioxidant, anti-inflammatory, and analgesic properties of the AgNPs and Ag-amoxi conjugates through in vivo and in vitro analysis. The Ag-amoxi conjugates showed better antibacterial potential against Streptococcus Pneumoniae (S.P), Staphylococcus aureus (S.A), Pseudomonas aeruginosa (P.A), and Methicillin resistance Staphylococcus aureus (MRSA) strain both the drug and AgNPs. Similarly, in vivo anti-inflammatory studies revealed that both Ag-amoxi (68 %) and AgNPs (64 %) had strong anti-inflammatory effects, with (***p < 0.001) significance at a dose of 10 mg kg−1 body weight as compared to standard, amoxicillin (45 %), and flavonoids extract (48 %) at a dose of 100 mg kg−1. The findings of the antinociceptive activities (writhing and hot plate tests) demonstrated that the Ag-amoxi conjugates produced fewer writhing (15 in 20 s) and a shorter latency time of 22 s as compared to vehicle-treated (tramadol) animals, amoxicillin, and P.E at much lower doses. In vitro antioxidant studies revealed that the Ag-amoxi conjugate has the potential to be used as an antioxidant with an IC50 value of 43.58, compared with AgNPs (46.34), amoxicillin (58.17), compared to the standard of ascorbic acid (34.14). ConclusionThese results reveals that these biologically inspired AgNPs and Ag-amoxi conjugate could be used to improve antibiotic efficiency and could play a critical role in addressing the multidrug resistance problem in coming years.

Near Infrared-Triggered Nitric Oxide-Release Nanovesicles with Mild-Photothermal Antibacterial and Immunomodulation for Healing MRSA-Infected Diabetic Wounds.

Bacterial infection-induced excessive inflammation is a major obstacle in diabetic wound healing. Nitric oxide (NO) exhibits significant antibacterial activity but is extremely deficient in diabetes. Hence, a near-infrared (NIR)-triggered NO release system is constructed through codelivery of polyarginine (PArg) and gold nanorods (Au) in an NIR-activatable methylene blue (MB)polypeptide-assembled nanovesicle (Au/PEL-PBA-MB/PArg). Upon NIR irradiation, the quenched MB in the nanovesicles is photoactivated to generate more reactive oxygen species (ROS) to oxidize PArg and release NO in an on-demand controlled manner. With the specific bacterial capture of phenylboronic acid (PBA), NO elevated membrane permeability and boosted bacterial vulnerability in the photothermal therapy (PTT) of the Au nanorods, which is displayed by superior mild PTT antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) at temperatures<49.7°C in vitro. Moreover, in vivo, the antibacterial nanovesicles greatly suppressed the burst of MRSA-induced excessive inflammation, NO relayed immunomodulated macrophage polarization from M1 to M2, and the excessive inflammatory phase is successfully transferred to the repair phase. In cooperation with angiogenesis by NO, tissue regeneration is accelerated in MRSA-infected diabetic wounds. Therefore, nanoplatform has considerable potential for accelerating the healing of infected diabetic wounds.

Antimicrobial Susceptibility of Methicillin-resistant Staphylococcus Aureus and Methicillin-sensitive Staphylococcus Aureus in a Pediatric Tertiary Care Hospital in Southern India

Objectives: To determine the current antimicrobial sensitivity profile of MRSA and compare it with the antimicrobial sensitivity of MSSA (Methicillin Sensitive Staphylococcus aureus) Material and Methods: Antimicrobial resistance in Staphylococcus aureus is a global public health concern. Methicillin-resistant Staphylococcus aureus (MRSA) is often resistant to the many classes of antibiotics compared to the methicillin-sensitive Staphylococcus aureus (MSSA). Five hundred and fifty S. aureus isolates obtained from clinical samples of pediatric patients were studied to determine the difference in the antimicrobial susceptibility between MRSA and MSSA. Results: Out of 550 S. aureus isolates, 59.3% were MSSA, and 40.7% were MRSA. The antimicrobial sensitivity to ciprofloxacin, gentamicin, clindamycin, erythomycin, tetracycline of MSSA was 26.4% , 93.6%, 81.5%, 61.2%, 95.4% respectively, and that of MRSA was 4.9%, 56.2%, 58%, 31%, 89.8% respectively. Conclusion: Antimicrobial sensitivity to ciprofloxacin, gentamicin, clindamycin, erythromycin, and tetracycline were significantly higher in MSSA than in MRSA.

Nanoarchitectonics of in Situ Antibiotic-Releasing Acicular Nanozymes for Targeting and Inducing Cuproptosis-like Death to Eliminate Drug-Resistant Bacteria.

A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of in vitro experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the methicillin-resistant Staphylococcus aureus (MRSA) cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly "capture" MRSA in liquid environments, releasing ROS, VAN and Cu2+ on bacterial surfaces to break down the MRSA barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu2+ causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.

Multifunctional Chi-Ag@HMPB@CBD nanocomposites for eradicating multidrug-resistant bacteria and promoting diabetic damaged tissue repair

Injured tissues are vulnerable to polymicrobial infection, resulting in insufficient blood supply, excessive oxidative stress, and inflammation, seriously affecting skin regeneration. Therefore, there is an urgent need to develop effective strategies to treat multiple bacterial infections and damaged tissues and tissue repair for clinical treatment. Herein, we designed new nano-complexes of Chi-Ag@HMPB@CBD NPs via hollow mesoporous Prussian blue nanoparticles (HMPB NPs) loaded with cannabidiol (CBD) and chitosan-modified silver nanoparticles (Chi-Ag NPs) to treat multiple bacterial infected damaged tissues. In vitro experiments show that Chi-Ag@HMPB@CBD NPs synergizes with CBD and Chi-Ag NPs to effectively kill the mixture of Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) via disrupting the cell membranes and established biofilms. Meanwhile, Chi-Ag@HMPB@CBD NPs can decompose H2O2 and increase O2 levels, thereby alleviating microenvironmental hypoxia and protecting cells from oxidative stress damage. Moreover, Chi-Ag@HMPB@CBD NPs can promote Human Umbilical Vein Endothelial Cells (HUVECs) proliferation, migration, and neovascularization by inhibiting Matrix Metalloprotein-9 (MMP-9) expression. In vivo experiments show that Chi-Ag@HMPB@CBD NPs exhibit high efficacy against mixed infections of E. coli and MRSA, accelerating damaged tissue repair via upregulating levels of Vascular Endothelial Growth Factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD31). Collectively, this study demonstrates that Chi-Ag@HMPB@CBD NPs are versatile nanomaterials with a great potential in clinical treatment of mixed bacterial-infected damaged tissue repair.