Secondary Amine Pendant ß-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking ß-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial ß-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.

Application of Supercritical Solvent Impregnation for Production of Zeolite Modified Starch-Chitosan Polymers with Antibacterial Properties.

In the present study, supercritical solvent impregnation (SSI) has been applied to incorporate thymol into bio-composite polymers as a potential active packaging material. Thymol, a natural component with a proven antimicrobial activity, was successfully impregnated into starch-chitosan (SC) and starch-chitosan-zeolite (SCZ) films using supercritical carbon dioxide (scCO2) as a solvent. Experiments were performed at 35 °C, pressures of 15.5 and 30 MPa, and an impregnation time in the range of 4-24 h. The highest impregnation yields of SC films with starch to chitosan mass ratios of 1:1 and 1:2 were 10.80% and 6.48%, respectively. The addition of natural zeolite (15-60%) significantly increased the loading capacity of films enabling thymol incorporation in a quantity of 16.7-27.3%. FTIR and SEM analyses were applied for the characterization of the films. Mechanical properties and water vapor permeability of films before and after the impregnation were tested as well. Thymol release kinetics in deionized water was followed and modeled by the Korsmeyer-Peppas and Weibull model. SCZ films with thymol loading of approximately 24% exhibited strong antibacterial activity against E. coli and methicillin-resistant Staphylococcus (S.) aureus (MRSA).

The Widely Used Antimicrobial Triclosan Induces High Levels of Antibiotic Tolerance In Vitro and Reduces Antibiotic Efficacy up to 100-Fold In Vivo.

The antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment. Approximately 75% of adults in the United States have detectable levels of the compound in their urine, with a sizeable fraction of individuals (>10%) having urine concentrations equal to or greater than the minimal inhibitory concentration for Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Previous work has identified connections between defects in fatty acid synthesis and accumulation of the alarmone guanosine tetraphosphate (ppGpp), which has been repeatedly associated with antibiotic tolerance and persistence. Based on these data, we hypothesized that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics. Here we report that clinically relevant concentrations of triclosan increased E. coli and MRSA tolerance to bactericidal antibiotics as much as 10,000-fold in vitro and reduced antibiotic efficacy up to 100-fold in a mouse urinary tract infection model. Genetic analysis indicated that triclosan-mediated antibiotic tolerance requires ppGpp synthesis but is independent of growth. These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.

Pilot Study to Evaluate the Adjunct Use of a Povidone-Iodine Topical Antiseptic in Patients with Soft Tissue Abscesses.

BACKGROUND: Povidone-iodine (PVP-I) antiseptic solutions have been shown to be effective against methicillin-resistant Staphylococcal aureus, a common cause of superficial skin abscesses. OBJECTIVES: Our objective was to study the feasibility of using PVP-I as a treatment adjunct in patients with superficial skin abscesses and determine if it confers any benefit over incision and drainage (I&D) alone. METHODS: This was a randomized controlled pilot study of adult patients with an uncomplicated skin abscess. Patients were randomized to PVP-I or standard treatment. All patients had I&D and abscess packing. Patients randomized to PVP-I were instructed on daily application of the agent to hands, wound, and surrounding skin with dressing changes. Subjects returned at 48-72 h and 7-10 days and followed-up by phone at 30 days. The primary outcome was clinical cure 7-10 days after I&D. The secondary outcomes were rate of development of new skin lesions and spread in household contacts within 30 days. RESULTS: Clinical cure occurred in 91.3% of patients in the standard group vs. 88.2% of patients in the PVP-I group (difference, 3.1%; 95% confidence interval [CI] -10.7 to 16.8; p = 0.53). There was a significantly higher adverse event rate in the group who received PVP-I (59.6%) vs. standard care (26.5%) (difference 33.1%, 95% CI 13.2-50.2; p < 0.001). CONCLUSIONS: There was no difference in clinical cure rates among patients using PVP-I (88.2%) vs. standard care (91.3%) after I&D. There were no major adverse events, but the addition of PVP-I was commonly associated with local skin irritation.

Alterations in human neutrophil function caused by bisphenol A.

Bisphenol A (BPA) is a synthetic, organic compound frequently present in consumer plastics, including plastic-lined cans, water bottles, toys, and teeth sutures. Previous studies have shown that BPA can produce adverse health effects that include defects in reproductive function and altered prenatal/childhood development. However, little is known regarding the effects of BPA on immune function. In this study, we assessed the effect of BPA on human neutrophils, a critical component of the innate immune system's defense against pathogens. We found that BPA induces a concentration-dependent increase in reactive oxygen species (ROS) generation by neutrophils, which is inhibited by the estrogen receptor-ß antagonist PHTPP. Furthermore, incubation with the membrane-permeable calcium chelator BAPTA-AM and/or removal of extracellular calcium inhibited BPA-induced ROS production, indicating that the process is calcium dependent. Transwell chemotaxis assays revealed that BPA exposure reduces the chemotactic capacity of neutrophils in a gradient of the bacterial cell wall component f-Met-Leu-Phe, a potent chemoattractant. Exposure to BPA also inhibits the ability of neutrophils to kill methicillin-resistant Staphylococcus aureus, a leading human pathogen. Our findings reveal that BPA alters the in vitro function of neutrophils, including ROS production, chemotaxis, and bacterial killing, and raises the possibility of altered innate immunity in vivo, especially in those with compromised immune function and who can be exposed to BPA in a wide variety of products.

An efficient antimicrobial depot for infectious site-targeted chemo-photothermal therapy.

BACKGROUND: Silver and photothermal therapy (PTT) have been widely used for eradicating the drug-resistant bacteria. However, the risks of excess of silver for humans and the low efficiency of PTT still limit their in vivo therapeutic application. Integration of two distinctive bactericides into one entity is a promising platform to improve the efficiency of antimicrobial agents. RESULTS: In this study, a chemo-photothermal therapeutic platform based on polydopamine (PDA)-coated gold nanorods (GNRs) was developed. The PDA coating acquired high Ag+ ions loading efficiency and Cy5-SE fluorescent agent labeled glycol chitosan (GCS) conjugation (Ag+-GCS-PDA@GNRs). This platform became positively charged in the low pH environment of the abscess, allowing their accumulation in local infection site as revealed by thermal/florescence imaging. The loaded Ag+ ions was released in a pH-sensitive manner, resulting in selective Ag+ ions delivery to the abscess environment (pH ~ 6.3). More importantly, the ultralow dose of Ag+ ions could effectively damage the bacterial membrane, causing the permeability increase and the heat resistance reduction of the cell membrane, leading to the large improvement on bactericidal efficiency of PTT. On the other hand, the hyperthermia could trigger more Ag+ ions release, resulting in further improvement on bactericidal efficiency of chemotherapy. Combinational chemo-hyperthermia therapy of Ag+-GCS-PDA@GNRs could thoroughly ablate abscess and accelerate wound healing via a synergistic antibacterial effect. CONCLUSIONS: Our studies demonstrate that Ag+-GCS-PDA@GNRs is a robust and practical platform for use in chemo-thermal focal infection therapy with outstanding synergistic bacteria ablating.

Liposome containing cinnamon oil with antibacterial activity against methicillin-resistant Staphylococcus aureus biofilm.

The global burden of bacterial disease remains high and is set against a backdrop of increasing antimicrobial resistance. There is a pressing need for highly effective and natural antibacterial agents. In this work, the anti-biofilm effect of cinnamon oil on methicillin-resistant Staphylococcus aureus was evaluated. Then, cinnamon oil was encapsulated in liposomes to enhance its chemical stability. The anti-biofilm activities of the liposome-encapsulated cinnamon oil against MRSA biofilms on stainless steel, gauze, nylon membrane and non-woven fabrics were evaluated by colony forming unit determination. Scanning electron microscopy and laser scanning confocal microscopy analyses were employed to observe the morphological changes in MRSA biofilms treated with the encapsulated cinnamon oil. As a natural and safe spice, the cinnamon oil exhibited a satisfactory antibacterial performance on MRSA and its biofilms. The application of liposomes further improves the stability of antimicrobial agents and extends the action time.

Outcomes of an Oral Care Protocol in Postmechanically Ventilated Patients.

BACKGROUND: Oral care is standard practice to prevent hospital-associated infections while patients are intubated and in the intensive care unit. Following extubation and transfer, infections remain an important risk for patients, but less attention is paid to oral care. Few studies have assessed the impact of oral care in recently extubated acutely ill patients. AIMS: To develop an evidence-based oral care protocol for hospitalized patients and determine the impact of this protocol on health outcomes in recently extubated patients. METHODS: In this randomized controlled trial, subjects were randomized to usual care or an intervention protocol that included tooth brushing, tongue scraping, flossing, mouth rinsing, and lip care. Major outcome measures were the revised THROAT (R-THROAT; oral cavity assessment) and overall prevalence of methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus on oral cultures. RESULTS: Seventy-four subjects were randomized. As measured by the R-THROAT, oral cavity health improved over time in both groups, but the intervention group demonstrated significantly more improvement than the control group (R-THROAT score improved by 1.97 intervention vs. 0.87 control; p = .04). Two categories, tongue and mouth comfort, demonstrated the most significant improvement. There was no difference in MSSA/MRSA colonization between the groups at the conclusion of the study. Overall, subjects in the intervention group were more satisfied with their protocol than subjects in the usual care group. LINKING EVIDENCE TO ACTION: This study offers an important evaluation of an oral care protocol after extubation. Results demonstrated improvement in the oral cavity assessment with the designed oral care protocol. Patients expressed a preference for the intervention protocol, which included a battery-operated toothbrush, higher-quality toothpaste and mouth rinse, tongue scraper, floss, and lip balm. The implementation of an oral care protocol specifically addressing patients in the immediate postintubation is essential.

Efficacy of skin and nasal povidone-iodine preparation against mupirocin-resistant methicillin-resistant Staphylococcus aureus and S. aureus within the anterior nares.

Mupirocin decolonization of nasal Staphylococcus aureus prior to surgery decreases surgical-site infections; however, treatment requires 5 days, compliance is low, and resistance occurs. In 2010, 3M Company introduced povidone-iodine (PVP-I)-based skin and nasal antiseptic (Skin and Nasal Prep [SNP]). SNP has rapid, broad-spectrum antimicrobial activity. We tested SNP's efficacy using full-thickness tissue (porcine mucosal [PM] and human skin) explant models and human subjects. Prior to or following infection with methicillin-resistant Staphylococcus aureus (MRSA) (mupirocin sensitive and resistant), explants were treated with Betadine ophthalmic preparation (Bet), SNP, or mupirocin (Bactroban nasal ointment [BN]) or left untreated. One hour posttreatment, explants were washed with phosphate-buffered saline (PBS) plus 2% mucin. One, 6, or 12 h later, bacteria were recovered and enumerated. Alternatively, following baseline sampling, human subjects applied two consecutive applications of SNP or saline to their anterior nares. One, 6, and 12 h after application of the preparation (postprep), nasal swabs were obtained, and S. aureus was enumerated. We observed that treatment of infected PM or human skin explants with SNP resulted in >2.0 log10 CFU reduction in MRSA, regardless of mupirocin sensitivity, which was significantly different from the values for BN- and Bet-treated explants and untreated controls 1 h, 6 h, and 12 h after being washed with PBS plus mucin. Swabbing the anterior nares of human subjects with SNP significantly reduced resident S. aureus compared to saline 1, 6, and 12 h postprep. Finally, pretreatment of PM explants with SNP, followed by a mucin rinse prior to infection, completely prevented MRSA infection. We conclude that SNP may be an attractive alternative for reducing the bioburden of anterior nares prior to surgery.

Evaluation of a nisin-eluting nanofiber scaffold to treat Staphylococcus aureus-induced skin infections in mice.

Staphylococcus aureus is a virulent pathogen and a major causative agent of superficial and invasive skin and soft tissue infections (SSSTIs). Antibiotic resistance in S. aureus, among other bacterial pathogens, has rapidly increased, and this is placing an enormous burden on the health care sector and has serious implications for infected individuals, especially immunocompromised patients. Alternative treatments thus need to be explored to continue to successfully treat infections caused by S. aureus, including antibiotic-resistant strains of S. aureus. In this study, an antimicrobial nanofiber wound dressing was generated by electrospinning nisin (Nisaplin) into poly(ethylene oxide) and poly(d,l-lactide) (50:50) blend nanofibers. Active nisin diffused from the nanofiber wound dressings for at least 4 days in vitro, as shown by consecutive transfers onto plates seeded with strains of methicillin-resistant S. aureus (MRSA). The nisin-containing nanofiber wound dressings significantly reduced S. aureus Xen 36 bioluminescence in vivo and viable cell numbers in a murine excisional skin infection model. The bacterial burden of wounds treated with nisin-containing nanofiber wound dressings was 4.3 × 10(2) CFU/wound, whereas wounds treated with control nanofiber wound dressings had 2.2 × 10(7) CFU/wound on the last day of the trial (day 7). Furthermore, the wound dressings stimulated wound closure of excisional wounds, and no adverse effects were observed by histological analysis. Nisin-containing nanofiber wound dressings have the potential to treat S. aureus skin infections and to potentially accelerate wound healing of excisional wounds.

Use of copper alloy for preventing transmission of methicillin-resistant Staphylococcus aureus contamination in the dermatology ward.

Metallic copper has been shown significantly to reduce methicillin-resistant Staphylococcus aureus (MRSA) contamination of the ambient surroundings of the beds of MRSA-carrying patients in dermatology wards. The aim of this study was to determine whether a bed sheet made of copper-coated film will reduce the spread of MRSA contamination in the environment of a heavily-colonized patient. The bacterial count was highest on the bed sheet. MRSA cell counts on the surface of the non-film-coated control sheet were high (6,600-11,000 colony forming units (cfu)), but those on the copper film were considerably lower (20-130 cfu). Use of metallic copper on the bed sheets of patients who are likely to be a source of MRSA contamination may help to prevent the spread of MRSA contamination in hospital wards.

Methicillin-resistant Staphylococcus aureus ST398 contamination and transmission in pigs after a low dose inoculation.

AIMS: Methicillin-resistant Staphylococcus aureus (MRSA) ST398 has recently been described as a zoonotic agent. Its transmission between animals seems to be a pivotal factor in its emergence and dissemination. This experimental trial was performed to describe MRSA ST398 contamination and transmission in pigs after a low dose inoculation. METHODS AND RESULTS: Twelve specific pathogen-free (SPF) pigs were randomly divided between two separate pens. Three pigs in each pen received a nasal inoculation of 2 × 10(4) colony-forming units per animal, and three naïve pigs were left in contact with them. Every 2 days and at necropsy, different samples were screened for MRSA. It was detected in nasal swabs from five inoculated and three naïve contact pigs, as early as 1 day after inoculation. MRSA was also found in environmental wipes but never in faecal samples. At necropsy, MRSA was detected in the lymph nodes of two contact pigs and in the tonsils and lymph nodes of three inoculated pigs. Twelve other SPF pigs were included as negative control in a separate room. CONCLUSION: This experiment showed that inoculation of a low dose of MRSA ST398 could lead to the horizontal transmission of the bacterium between pigs, the contamination of mandibular lymph nodes and the contamination of the environment without faecal carriage. SIGNIFICANCE AND IMPACT OF THE STUDY: The minimal inoculated dose via nasal route to observe transmission of MRSA ST398 between pigs is equal or lower to 2 × 10(4) colony-forming units per animal, and faecal excretion seems not to be a necessary condition for horizontal transmission.

Community-associated methicillin-resistant Staphylococcus aureus and athletes.

The remarkable ability of Staphylococcus aureus to develop antibiotic resistance in conjunction with the emergence of highly virulent and/or transmissible strains has established the pathogen as a leading cause of human bacterial infections worldwide. Historically, methicillin-resistant S aureus (MRSA) was found almost exclusively in hospitals and/or health care-related facilities. However, in the late 1990s, community-associated MRSA strains emerged in the United States and rapidly became the leading cause of community-associated bacterial infections. An enhanced understanding of the pathogenesis and epidemiology of this bacterium is fundamental for the prevention and/or treatment of community-associated MRSA infections. This review highlights salient features of S aureus biology that contribute to the exceptional ability of this pathogen to cause human disease, as well as discusses, in brief, the established approaches for treatment and prevention of infection.

Two-stage total hip arthroplasty: how often does it control methicillin-resistant infection?

BACKGROUND: Methicillin-resistant hip infections are increasingly common. Reports of the surgical management of these patients using two-stage THA show variable control of infection, but all reports used static spacers. QUESTIONS/PURPOSES: We therefore determined (1) the rate of successful control of infection and (2) function in patients with methicillin-resistant infection treated with a two-stage THA using an articulated cement spacer during the first stage. METHODS: We retrospectively reviewed 50 patients who had a two-stage revision THA for methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis infection. Twelve patients died, leaving 38 for review. All eligible patients completed quality-of-life outcome questionnaires (WOMAC, SF-12, Oxford-12, UCLA activity score, hip and knee satisfaction score). Minimum followup was 24 months after the second stage (mean, 58 months; range, 24-123 months). RESULTS: Of the 38 patients, eight (21%) had recurrence of their infection requiring further revision surgery. Of the remaining 27 patients, the mean WOMAC was 62, mean Oxford-12 60, mean UCLA activity score 4.3, and mean hip and knee satisfaction score 66. CONCLUSIONS: We found a treatment failure rate of 21% for patients with methicillin-resistant S. aureus or methicillin-resistant S. epidermidis infection. This is a higher rate than reported for two-stage THA for studies including patients infected with both nonresistant and resistant organisms. The functional scores for patients were also lower than those reported in the literature. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

An antibacterial coated polymer prevents biofilm formation and implant-associated infection.

To prevent infections associated with medical implants, various antimicrobial silver-coated implant materials have been developed. However, these materials do not always provide consistent antibacterial effects in vivo despite having dramatic antibacterial effects in vitro, probably because the antibacterial effects involve silver-ion-mediated reactive oxygen species generation. Additionally, the silver application process often requires extremely high temperatures, which damage non-metal implant materials. We recently developed a bacteria-resistant coating consisting of hydroxyapatite film on which ionic silver is immobilized via inositol hexaphosphate chelation, using a series of immersion and drying steps performed at low heat. Here we applied this coating to a polymer, polyetheretherketone (PEEK), and analyzed the properties and antibacterial activity of the coated polymer in vitro and in vivo. The ionic silver coating demonstrated significant bactericidal activity and prevented bacterial biofilm formation in vitro. Bio-imaging of a soft tissue infection mouse model in which a silver-coated PEEK plate was implanted revealed a dramatic absence of bacterial signals 10 days after inoculation. These animals also showed a strong reduction in histological features of infection, compared to the control animals. This innovative coating can be applied to complex structures for clinical use, and could prevent infections associated with a variety of plastic implants.

Liposome encapsulated surfactant abetted copper nanoparticles alleviates biofilm mediated virulence in pathogenic Pseudomonas aeruginosa and MRSA.

In the present study lipopeptide biosurfactant with high emulsification capacity produced by human skin bacterium Paenibacillus thiaminolyticus was purified and subjected to FTIR and NMR spectral analysis which gave evidence of the active characteristics of the surfactant. To augment the antivirulent potential further, the mixer of copper and copper oxide nanoparticles (CuNPs) was synthesized, and characterized by UV-Visible spectroscopy, SEM-EDAX, TEM, and Zeta analysis. Here, we attempted to enhance the antimicrobial and antibiofilm activity with the assistance of encapsulated preparation of lipopeptide and CuNPs in multilamellar liposomes. The proposed mechanism of action of lipopeptide and CuNPs liposomal preparation negatively influences the cell metabolism, secreted virulence such as staphyloxanthin, pyocyanin, and extracellular polysaccharides. The significant decline in the growth of MRSA and P. aeruginosa in both planktonic form and biofilm by lipopeptide and CuNPs treatment were visualized using scanning electron microscopy and High content screening imaging system. In vivo studies revealed that treatment with lipopeptide and CuNPs in multilamellar liposomes extended the lifespan of infected Caenorhabditis elegans by about 75%. Therefore, this study typifies lipopeptide and CuNPs could credibly be a substantial substitute over conventional antibiotics in averting the biofilm associated pathogenesis of MRSA and P. aeruginosa.

Targeting Antibacterial Effect and Promoting of Skin Wound Healing After Infected with Methicillin-Resistant Staphylococcus aureus for the Novel Polyvinyl Alcohol Nanoparticles.

INTRODUCTION: Topical agents typically remain in the wound site for time duration that are too short to effectively eradicate MRSA tradition formation of BZK that can be maintained within the wound site for longer time periods, should be more effective. METHODS: The novel chitosan and poly (D,L-lactide-co-glycoside) nanoparticles loaded with benzalkonium bromide (BZK) were designed, for the promotion wound healing after MRSA infection. The physical characterization of these nanoparticles, as well as their antibacterial activity in vitro, release profile in simulated wound fluid, cell toxicity, anti-biofilm activity, and their ability to improve the skin wound healing in a mouse model were also studied. RESULTS: These novel nanoparticles were found to have a significant antibacterial activity (p<0.01), both in vitro and in vivo test. The stronger anti-biofilm ability of the nanoparticles to inhibit the formation of bacterial biofilms, at a concentration of 3.33 µg/mL, and clear existing bacterial biofilms, at a concentration of 5 mg/mL, compared with its water solution. In addition, significant damage to bacterial cell walls also was found, providing insight into the mechanism of antibacterial activity. CONCLUSION: Taken together, these results demonstrated the ability of BZK-loaded nanoparticles in the promotion of skin wound healing with MRSA infection. The current findings open a new avenue for nanomedicine development and future clinical applications in the treatment of wounds.

Photodynamic Coatings on Polymer Microfibers for Pathogen Inactivation: Effects of Application Method and Composition.

A substantial increase in the risk of hospital-acquired infections (HAIs) has greatly impacted the global healthcare industry. Harmful pathogens adhere to a variety of surfaces and infect personnel on contact, thereby promoting transmission to new hosts. This is particularly worrisome in the case of antibiotic-resistant pathogens, which constitute a growing threat to human health worldwide and require new preventative routes of disinfection. In this study, we have incorporated different loading levels of a porphyrin photosensitizer capable of generating reactive singlet oxygen in the presence of O2 and visible light in a water-soluble, photo-cross-linkable polymer coating, which was subsequently deposited on polymer microfibers. Two different application methods are considered, and the morphological and chemical characteristics of these coated fibers are analyzed to detect the presence of the coating and photosensitizer. To discern the efficacy of the fibers against pathogenic bacteria, photodynamic inactivation has been performed on two different bacterial strains, Staphylococcus aureus and antibiotic-resistant Escherichia coli, with population reductions of >99.9999 and 99.6%, respectively, after exposure to visible light for 1 h. In response to the current COVID-19 pandemic, we also confirm that these coated fibers can inactivate a human common cold coronavirus serving as a surrogate for the SARS-CoV-2 virus.

Evaluation of hypocrellin A-loaded lipase sensitive polymer micelles for intervening methicillin-resistant Staphylococcus Aureus antibiotic-resistant bacterial infection.

There is an urgent need for new antibacterial strategies to overcome the emergence of antibiotic resistance. Antibacterial photodynamic therapy (APDT) may be an effective method to deliver photosensitizers for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report that the photosensitizer hypocrellin A (HA) loaded into lipase-sensitive methoxy poly (ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) micelles showed high anti-MRSA activity in vitro and in vivo by PDT. Once the micelles come into contact with bacteria that secrete lipase, the PCL is degraded to release HA. Our results showed that the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of mPEG-PCL/HA micelles after light irradiation were 0.69 and 1.38 mg/L (HA concentration), respectively. In the dark, the MIC and MBC of the micelles were 250 and 500 mg/L (HA concentration), respectively. The fluorescent stain results further demonstrated the photodynamic antibacterial activity of mPEG-PCL/HA micelles. The survival rate of mice subjected to experimental acute peritonitis increased to 86% after treated with the micelles. The polymeric micelles showed low hemolytic activity and biocompatibility, simultaneously preventing aggregation in vivo and enhancing the water solubility of HA. Thus, the photosensitizer HA loaded micelles could be used as APDT for infections caused by bacteria without antibiotic resistance.

Liquid Exfoliation of Atomically Thin Antimony Selenide as an Efficient Two-Dimensional Antibacterial Nanoagent.

The ever-growing global crisis of multidrug-resistant bacteria has triggered a tumult of activity in the design and development of antibacterial formulations. Here, atomically thin antimony selenide nanosheets (Sb2Se3 NSs), a minimal-toxic and low-cost semiconductor material, were explored as a high-performance two-dimensional (2D) antibacterial nanoagent via a liquid exfoliation strategy integrating cryo-pretreatment and polyvinyl pyrrolidone (PVP)-assisted exfoliation. When cultured with bacteria, the obtained PVP-capped Sb2Se3 NSs exhibited intrinsic long-term antibacterial capability, probably due to the reactive oxygen species generation and sharp edge-induced membrane cutting during physical contact between bacteria and nanosheets. Upon near-infrared laser irradiation, Sb2Se3 NSs achieved short-time hyperthermia sterilization because of strong optical absorption and high photothermal conversion efficiency. By virtue of the synergistic effects of these two broad-spectrum antibacterial mechanisms, Sb2Se3 NSs exhibited high-efficiency inhibition of conventional Gram-negative Escherichia coli, Gram-positive methicillin-resistant Staphylococcus aureus, and wild bacteria from a natural water pool. Particularly, these three categories of bacteria were completely eradicated after being treated with Sb2Se3 NSs (300 µM) plus laser irradiation for only 5 min. In vivo wound healing experiment further demonstrated the high-performance antibacterial effect. In addition, Sb2Se3 NSs depicted excellent biocompatibility due to the biocompatible element constitute and bioinert PVP modification. This work enlightened that atomically thin Sb2Se3 NSs hold great promise as a broad-spectrum 2D antibacterial nanoagent for various pathogenic bacterial infections.