Treatment Of Drug-resistant Bacterial Infections Research Articles

A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA-induced Sepsis and Chronic Wound Infection.

The rising prevalence of global antibiotic resistance evokes the urgent need for novel antimicrobial candidates. Cationic lipopeptides have attracted much attention due to their strong antimicrobial activity, broad-spectrum and low resistance tendency. Herein, a library of fluoro-lipopeptide amphiphiles was synthesized by tagging a series of cationic oligopeptides with a fluoroalkyl tail via a disulfide spacer. Among the lipopeptide candidates, R6F bearing six arginine moieties and a fluorous tag shows the highest antibacterial activity, and it exhibits an interesting fluorine effect as compared to the non-fluorinated lipopeptides. The high antibacterial activity of R6F is attributed to its excellent bacterial membrane permeability, which further disrupts the respiratory chain redox stress and cell wall biosynthesis of the bacteria. By co-assembling with lipid nanoparticles, R6F showed high therapeutic efficacy and minimal adverse effects in the treatment of MRSA-induced sepsis and chronic wound infection. This work provides a novel strategy to design highly potent antibacterial peptide amphiphiles for the treatment of drug-resistant bacterial infections.

Expert Opinion on the Prescription Practice of Carbapenem Antibiotics for the Treatment of Drug-Resistant Bacterial Infections in Indian Settings

Objective: The current survey-based study aims to gather expert opinions on the prescription practice of carbapenem antibiotics for the treatment of drug-resistant bacterial infections in Indian clinical settings.
 Methods: The cross-sectional, multiple-response questionnaire-based survey involving professionals with expertise in treating pathogenic illnesses was carried out between 2022 and 2023. The questionnaire comprised 25 questions, the majority of which dealt with the use of antibiotics as monotherapy and in various combinations to treat pathogenic illnesses.
 Results: Out of 302 survey participants, 83% of them preferred meropenem medications more frequently than imipenem, biapenem, doripenem, and other antibiotics to treat pathogenic infections. For the management of multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant (PDR) infections, approximately 54% of the respondents preferred the administration of 1 gm of IV meropenem in 2 to 3 divided doses. About 61% of the responders suggested using IV meropenem together with colistin to treat infections. The combination of IV meropenem with β-lactams, aminoglycosides, tigecycline, colistin, and others was preferred by 91% of the respondents for the treatment of MDR, XDR, and PDR infections. For treating difficult intra-abdominal infections, meningitis, and urinary tract infections (UTIs), almost 43% of the respondents preferred meropenem in combination with sulbactam.
 Conclusion: The survey findings emphasize the prominent role of meropenem, either as a standalone treatment or in combination with other antibiotics in the management of challenging infections caused by MDR, XDR, or PDR pathogens. In specific scenarios involving difficult intra-abdominal infections, meningitis, and UTIs, clinicians recommended meropenem in combination with sulbactam antibiotics.

Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections

IntroductionThe design of precision antimicrobials aims to personalize the treatment of drug-resistant bacterial infections and avoid host microbiota dysbiosis. ObjectivesThis study aimed to propose an efficient de novo design strategy to obtain specifically targeted antimicrobial peptides (STAMPs) against methicillin-resistant Staphylococcus aureus (MRSA). MethodsWe evaluated three strategies designed to increase the selectivity of antimicrobial peptides (AMPs) for MRSA and mainly adopted an advanced hybrid peptide strategy. First, we proposed a traversal design to generate sequences, and constructed machine learning models to predict the anti-S. aureus activity levels of unknown peptides. Subsequently, six peptides were predicted to have high activity, among which, a broad-spectrum AMP (P18) was selected. Finally, the two targeting peptides from phage display libraries or lysostaphin were used to confer specific anti-S. aureus activity to P18. STAMPs were further screened out from hybrid peptides based on their in vitro and in vivo activities. ResultsAn advanced hybrid peptide strategy can enhance the specific and targeted properties of broad-spectrum AMPs. Among 25 assessed peptides, 10 passed in vitro tests, and two peptides containing one bacterial-entrapping peptide (BEP) and one STAMP passed an in vivo test. The lead STAMP (P18E6) disrupted MRSA cell walls and membranes, eliminated established biofilms, and exhibited desirable biocompatibility, systemic distribution and efficacy, and immunomodulatory activity in vivo. Furthermore, a bacterial-entrapping peptide (BEP, SP5) modified from P18, self-assembled into nanonetworks and rapidly entrapped MRSA. SP5 synergized with P18E6 to enhance antibacterial activity in vitro and reduced systemic MRSA infections. ConclusionsThis strategy may aid in the design of STAMPs against drug-resistant strains, and BEPs can serve as powerful STAMP adjuvants.

Design of phenothiazine-based cationic amphiphilic derivatives incorporating arginine residues: Potential membrane-active broad-spectrum antimicrobials combating pathogenic bacteria in vitro and in vivo

Multidrug-resistant bacteria infections pose an increasingly serious threat to human health, and the development of antimicrobials is far from meeting the clinical demand. It is urgent to discover and develop novel antibiotics to combat bacterial resistance. Currently, the development of membrane active antimicrobial agents is an attractive strategy to cope with antimicrobial resistance issues. In this study, the synthesis and biological evaluation of cationic amphiphilic phenothiazine-based derivatives were reported. Among them, the most promising compound 30 bearing a n-heptyl group and two arginine residues displayed potent bactericidal activity against both Gram-positive (MICs = 1.56 μg/mL) and Gram-negative bacteria (MICs = 3.125–6.25 μg/mL). Compound 30 showed low hemolysis activity (HC50 = 281.4 ± 1.6 μg/mL) and low cytotoxicity (CC50 ＞ 50 μg/mL) toward mammalian cells, as well as excellent salt resistance. Compound 30 rapidly killed bacteria by acting on the bacterial cell membrane and appeared less prone to resistance. Importantly, compound 30 showed potent in vivo efficacy in a murine model of bacterial keratitis. Hence, the results suggested compound 30 has a promising prospect as a broad-spectrum antibacterial agent for the treatment of drug-resistant bacterial infections.

The Potential of Bacteriophage-Antibiotic Combination Therapy in Treating Infections with Multidrug-Resistant Bacteria.

The growing threat of antibiotic resistance is a significant global health challenge that has intensified in recent years. The burden of antibiotic resistance on public health is augmented due to its multifaceted nature, as well as the slow-paced and limited development of new antibiotics. The threat posed by resistance is now existential in phage therapy, which had long been touted as a promising replacement for antibiotics. Consequently, it is imperative to explore the potential of combination therapies involving antibiotics and phages as a feasible alternative for treating infections with multidrug-resistant bacteria. Although either bacteriophage or antibiotics can potentially treat bacterial infections, they are each fraught with resistance. Combination therapies, however, yielded positive outcomes in most cases; nonetheless, a few combinations did not show any benefit. Combination therapies comprising the synergistic activity of phages and antibiotics and combinations of phages with other treatments such as probiotics hold promise in the treatment of drug-resistant bacterial infections.

Design, synthesis, and evaluation of novel pleuromutilin aryl acrylate derivatives as promising broad-spectrum antibiotics especially for combatting multi-drug resistant gram-negative bacteria

The emergence of drug-resistant strains presents a grave challenge for traditional antibiotics, underscoring the exigency of exploring novel antibacterial drugs. To address this, the present study endeavors to design and synthesize a collection of pleuromutilin aromatic acrylate derivatives, guided by combination principles. The antibacterial activity and structure-activity relationship of these derivatives were evaluated, and most of the derivatives displayed moderate to excellent antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Among these derivatives, 5g exhibited the strongest antibacterial activity, with MIC (minimum inhibitory concentration) values ranging from 1–32 μg/mL, and a MIC value against clinically isolated drug-resistant strains of 4–64 μg/mL. Additionally, 5g exhibited negligible cytotoxicity, superior anti-mycoplasma activity, and a greater propensity to perturb bacterial cell membranes. Notably, the administration of 5g resulted in an increased survival rate of MRSA (Methicillin-resistant Staphylococcus aureus)-infected mice, with an ED50 (median effective dose) value of 9.04 mg/kg. These results indicated the potential of 5g to be further developed as an antibacterial drug for the clinical treatment of drug-resistant bacterial infections.

MOF/polypeptide hybrid nanocomposites with pH/lipase dual responsive drug release and photodynamic effect for combination treatment of drug-resistant bacterial infection

Multi-drug resistant (MDR) bacterial infection has become one of the most serious health issues due to its high mortality rate. To address this problem, a novel metal–organic framework (MOF)/polypeptide hybrid nanocomposite was synthesised for the combined chemo-photodynamic therapy of MDR bacterial infection. A lipase-sensitive crosslinker was used to prepare the crosslinked polypeptide outer shell of the nanocomposite, and ciprofloxacin (CIP) and methylene blue (MB) were incorporated in the zeolite imidazole framework (ZIF)/poly-γ-glutamic acid (PGA) nanocomposites to form the combined therapeutic system (ZIF/PGA-C/M) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). The ZIF/PGA-C/M displayed a negative surface charge of −11.2 mV at physiological pH, indicating improved structural stability and biocompatibility. The pH/lipase dual responsive drug release showed that up to 99.4% CIP and 76.0 % MB were released at pH 5.5 in the presence of lipase from the ZIF/PGA-C/M. Moreover, the incorporated MB can effectively generate singlet oxygen (1O2) to kill the bacteria by a photodynamic effect under NIR irradiation. Remarkably, ZIF/PGA-C/M showed an efficient inhibition rate towards MRSA in both planktonic and biofilm phenotypes, and a synergistic therapeutic effect against MRSA infection in the mice model of skin infection.

New insights into the antimicrobial action and protective therapeutic effect of tirapazamine towards Escherichia coli-infected mice

Escherichia coli is an important pathogen responsible for numerous cases of diarrhoea worldwide. The bioreductive agent tirapazamine (TPZ), which was clinically used to treat various types of cancers, has obvious antibacterial activity against E. coli strains. In the present study, we aimed to evaluate the protective therapeutic effects of TPZ in E. coli-infected mice and provide insights into its antimicrobial action mechanism. The MIC and MBC tests, drug sensitivity test, crystal violet assay and proteomic analysis were used to detect the in vitro antibacterial activity of TPZ. The clinical symptoms of infected mice, tissue bacteria load, histopathological features and gut microbiota changes were regarded as indicators to evaluation the efficacy of TPZ in vivo. Interestingly, TPZ-induced the reversal of drug resistance in E. coli by regulating the expression of resistance-related genes, which may have an auxiliary role in the clinical treatment of drug-resistant bacterial infections. More importantly, the proteomics analysis showed that TPZ upregulated 53 proteins and downregulated 47 proteins in E. coli. Among these, the bacterial defence response-related proteins colicin M and colicin B, SOS response-related proteins RecA, UvrABC system protein A, and Holliday junction ATP-dependent DNA helicase RuvB were all significantly upregulated. The quorum sensing-related protein glutamate decarboxylase, ABC transporter-related protein glycerol-3-phosphate transporter polar-binding protein, and ABC transporter polar-binding protein YtfQ were significantly downregulated. The oxidoreductase activity-related proteins pyridine nucleotide-disulfide oxidoreductase, glutaredoxin 2 (Grx2), NAD(+)-dependent aldehyde reductase, and acetaldehyde dehydrogenase, which participate in the elimination of harmful oxygen free radicals in the oxidation-reduction process pathway, were also significantly downregulated. Moreover, TPZ improved the survival rate of infected mice; significantly reduced the bacteria load in the liver, spleen, and colon; and alleviated E. coli-associated pathological damages. The gut microbiota also changed in TPZ-treated mice, and these genera were considerably differentiated: Candidatus Arthromitus, Eubacterium coprostanoligenes group, Prevotellaceae UCG-001, Actinospica, and Bifidobacterium. TPZ may represent an effective and promising lead molecule for the development of antimicrobial agents for the treatment of E. coli infections.

Cu-GA-coordination polymer nanozymes with triple enzymatic activity for wound disinfection and accelerated wound healing

During the past few years, bacterial infection and oxidative stress have become important issues for wound healing. However, the emergence of numerous drug-resistant superbugs has had a serious impact on the treatment of infected wounds. Presently, the development of new nanomaterials has become one of the most important approaches to the treatment of drug-resistant bacterial infections. Herein, coordination polymer copper-gallic acid (Cu-GA) nanorods with multi-enzyme activity is successfully prepared for efficient wound treatment of bacterial infection, which can effectively promote wound healing. Cu-GA can be efficiently prepared by a simple solution method and had good physiological stability. Interestingly, Cu-GA shows enhanced multienzyme activity (peroxidase, glutathione peroxidase, and superoxide dismutase), which can produce a large number of reactive oxygen species (ROS) under acidic conditions while scavenging ROS under neutral conditions. In acidic environment, Cu-GA possesses POD (peroxidase)-like and glutathione peroxidase (GSH-Px)-like catalytic activities that is capable of killing bacteria; but in neutral environment, Cu-GA exhibits superoxide dismutase (SOD)-like catalytic activity that can scavenge ROS and promote wound healing. In vivo studies show that Cu-GA can promote wound infection healing and have good biosafety. Cu-GA contributes to the healing of infected wounds by inhibiting bacterial growth, scavenging reactive oxygen species, and promoting angiogenesis. Statement of significanceCu-GA-coordinated polymer nanozymes with multienzyme activity were successfully prepared for efficient wound treatment of bacterial infection, which could effectively promote wound healing. Interestingly, Cu-GA exhibited enhanced multienzyme activity (peroxidase, glutathione peroxidase, and superoxide dismutase), which could produce a large number of reactive oxygen species (ROS) under acidic conditions and scavenge ROS under neutral conditions. In vitro and in vivo studies demonstrated that Cu-GA was capable of killing bacteria, controlling inflammation, and promoting angiogenesis.

Entropy-Mediated High-Entropy MXenes Nanotherapeutics: NIR-II-Enhanced Intrinsic Oxidase Mimic Activity to Combat Methicillin-Resistant Staphylococcus Aureus Infection.

Bacterial infections, such as bacterial keratitis (BK) and subcutaneous abscess, pose significant challenges to global healthcare. Innovative and new antibacterial agents and antibacterial strategies are in demand to control infections in this era of high drug resistance. Nanotechnology gradually emerged as an economically feasible and effective anti-infection treatment. High-entropy MXenes (HE MXenes) are used to confer desirable properties with exposed active sites to high-entropy atomic layers, whose potential application in the field of biomedicine remains to be explored. Herein, we fabricate the monolayer HE MXenes by implementing transition metals with high entropy and low Gibbs free energy to fill the gap in the biocatalytic performance of non-high-entropy MXenes. HE MXenes are endowed with extremely strong oxidase mimic activity (Km = 0.227mM) and photothermal conversion efficiency (65.8%) in the second near-infrared (NIR-II) biowindow as entropy increases. Subsequently, HE MXenes realize NIR-II-enhanced intrinsic oxidase mimic activity for killing methicillin-resistant Staphylococcus aureus and rapidly removing the biofilm. Furthermore, HE MXenes can effectively treat BK and subcutaneous abscess infection induced by MRSA as nanotherapeutic agents with minuscule side effects. Overall, monolayer HE MXenes demonstrate promising clinical application potential in the treatment of drug-resistant bacterial infections and promote the healing of infected tissues. This article is protected by copyright. All rights reserved.

Antibacterial effect of rose bengal against colistin-resistant gram-negative bacteria.

Increasing drug resistance in Gram-negative bacteria presents significant health problems worldwide. Despite notable advances in the development of a new generation of β-lactams, aminoglycosides, and fluoroquinolones, it remains challenging to treat multi-drug resistant Gram-negative bacterial infections. Colistin (polymyxin E) is one of the most efficacious antibiotics for the treatment of multiple drug-resistant Gram-negative bacteria and has been used clinically as a last-resort option. However, the rapid spread of the transferable gene, mcr-1 which confers colistin resistance by encoding a phosphoethanolamine transferase that modifies lipid A of the bacterial membrane, threatens the efficacy of colistin for the treatment of drug-resistant bacterial infections. Colistin-resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae often reduce their susceptibility to other anti-Gram-negative bacterial agents. Thus, drugs effective against colistin-resistant strains or methods to prevent the acquisition of colistin-resistance during treatment are urgently needed. To perform cell-based screenings of the collected small molecules, we have generated colistin-resistant strains of E. coli, A. baumannii, K. pneumoniae, P. aeruginosa, and S. enterica Typhimurium. In-house MIC assay screenings, we have identified that rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) is the only molecule that displays unique bactericidal activity against these strains at low concentrations under illumination conditions. This article reports the antibacterial activity of a pharmaceutical-grade rose bengal against colistin-resistant Gram-negative bacteria.

A new approach to overcoming antibiotic-resistant bacteria: Traditional Chinese medicine therapy based on the gut microbiota.

With the irrational use of antibiotics and the increasing abuse of oral antibiotics, the drug resistance of gastrointestinal pathogens has become a prominent problem in clinical practice. Gut microbiota plays an important role in maintaining human health, and the change of microbiota also affects the activity of pathogenic bacteria. Interfering with antibiotic resistant bacteria by affecting gut microbiota has also become an important regulatory signal. In clinical application, due to the unique advantages of traditional Chinese medicine in sterilization and drug resistance, it is possible for traditional Chinese medicine to improve the gut microbial microenvironment. This review discusses the strategies of traditional Chinese medicine for the treatment of drug-resistant bacterial infections by changing the gut microenvironment, unlocking the interaction between microbiota and drug resistance of pathogenic bacteria.

Antibacterial Activity of Eravacycline Against Carbapenem-Resistant Gram-Negative Isolates in China: An in vitro Study.

Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, with a broad-spectrum antimicrobial activity, including against carbapenem-resistant gram-negative bacteria (CRGNB). However, the in vitro activity of eravacycline against CRGNB has not been well known in China. In this study, we analysed the antibacterial activity of eravacycline against CRGNB isolates in order to provide a theoretical basis for the clinical treatment. A total of 346 isolates of CRGNB were collected from two different tertiary care hospitals in Zhejiang, China. Carbapenem resistance genes of all isolates were detected by polymerase chain reaction. And we analysed the in vitro activity of eravacycline against CRGNB by antimicrobial susceptibility tests. In addition, the time-kill curves were generated to evaluate the antibacterial effect of tigecycline and eravacycline. Four different types of carbapenem-resistant isolates were collected, including 50 Escherichia coli isolates, 160 Klebsiella pneumoniae isolates, 42 Enterobacter cloacae complex isolates, and 94 Acinetobacter baumannii isolates. The carbapenem resistance genes were identified in 346 isolates, including bla KPC-2 (48.0%), bla OXA-23 (27.2%), bla NDM-1 (23.1%), and bla NDM-16 (0.3%). The antimicrobial susceptibility testing results showed that the minimum inhibitory concentration (MIC) values of 346 isolates were within the sensitivity range (≤0.0625~16 mg/L) and that the MIC50 or MIC90 of eravacycline was generally approximately 2-fold lower than tigecycline. In addition, the time-kill curves showed that the bactericidal effect of eravacycline was stronger than that of tigecycline against four different types of isolates. Our research indicated that eravacycline had a good antibacterial effect on CRGNB, which could provide a theoretical basis for the clinical treatment of drug-resistant bacterial infections in the future.

Recent developments in detection and therapeutic approaches for antibiotic-resistant bacterial infections.

Owing to the widespread emergence and proliferation of antibiotic-resistant bacteria, the therapeutic benefits of antibiotics have been reduced. In addition, the ongoing evolution of multidrug-resistant pathogens poses a challenge for the scientific community to develop sensitive analytical methods and innovative antimicrobial agents for the detection and treatment of drug-resistant bacterial infections. In this review, we have described the antibiotic resistance mechanisms that occur in bacteria and summarized the recent developments in detection strategies for monitoring drug resistance using different diagnostic methods in three aspects, including electrostatic attraction, chemical reaction, and probe-free analysis. Additionally, to understand the effective inhibition of drug-resistant bacterial growth by recent nano-antibiotics, the underlying antimicrobial mechanisms and efficacy of biogenic silver nanoparticles and antimicrobial peptides, which have shown promise, and the rationale, design, and potential improvements to these methods are also highlighted in this review. Finally, the primary challenges and future trends in the rational design of facile sensing platforms and novel antibacterial agents against superbugs are discussed.

Global trends and hotspots of phage therapy for bacterial infection: A bibliometric visualized analysis from 2001 to 2021.

Antibiotic resistance is one of the main global threats to human health, and just the development of new antimicrobial medications is not enough to solve the crisis. Phage therapy (PT), a safe and effective treatment method, has reignited the interest of researchers due to its efficacy in the clinical treatment of drug-resistant bacterial infections. There is, however, no bibliometric analysis of the overall trends on this topic. Therefore, this study aims to provide an overview of the current state of development and research in this area. We extracted all relevant publications from the Web of Science Core Collection (WoSCC) database between 2001 and 2021. We performed bibliometric analysis and visualization using CiteSpace, VOS viewer, and R software. Annual trends of publications, countries/regions distributions, institutions, funding agencies, co-cited journals, author contributions, core journals, references, and keywords were analyzed. A total of 6,538 papers were enrolled in this study, including 5,364 articles and 1,174 reviews. Publications have increased drastically from 61 in 2001 to 937 in 2021, with 3,659 articles published in the last 5 years. North America, Western Europe, and East Asia were significant contributor regions. The United States, China, and the United Kingdom were the most productive countries. The Polish Academy of Sciences was the most contributive institution. Frontiers in Microbiology and Applied and Environmental Microbiology were the most productive and co-cited journals. A. Gorski and R. Lavigne published most articles in this field, while V. A. Fischetti was the author with the most cited. Regarding keywords, research focuses include phage biology, phage against clinically important pathogens, phage lysis proteins, phage therapy, biofilm-related research, and recent clinical applications. Phage therapy is a potential strategy for combating antibiotic resistance, and it will provide us with an alternative therapeutic option for bacterial infection. According to global trends, the scientific output of PT in bacterial infections is increasing, with developed countries such as the United States leading the way in this area. Although the safety and efficacy of PT have been proven, more clinical trials on the phages against infectious diseases caused by various pathogens are still needed.

Promoting photothermal antibacterial activity through an excited-state intramolecular proton transfer process.

The construction of an efficient photothermal antibacterial platform is a promising strategy for the treatment of drug-resistant bacterial infections. Herein, through the introduction of excited-state intramolecular proton transfer to promote the photothermal effect, N-(2,4-dihydroxybenzylidene)-4-aminophenol (DOA)-polyvinyl alcohol (PVA) systems (DPVA) can reach 55 °C within 10 s under irradiation. They show superior antibacterial behavior against drug-resistant bacteria and a therapeutic effect on infected skin wounds with only 100 s of irradiation, much faster than those of reported photothermal materials (5-10 min). This work provides a convenient approach to fabricate broad-spectrum antibacterial wound dressings for treating bacteria-infected wounds, greatly contributing to the design and applications of photothermal antibacterial platforms.

Reactive oxygen species-mediated CuRuOX@HA hybrid nanozymes for multidrug-resistant bacterial infections with synergistic photothermal therapy.

Drug-resistant bacterial infections pose a serious threat to human life and health, especially multidrug-resistant bacterial infections are difficult to treat with currently available antibiotics. A number of evidences showed that reactive oxygen species (ROS) and photothermal therapy (PTT) can easily kill drug-resistant bacteria while they have not developed resistance to drugs. Inspired by good stability and high catalytic activity of nanozymes and in order to construct versatile nanozymes, the therapy of ROS was integrated with PTT. This study prepared a ROS-mediated copper-ruthenium oxide (CuRuOX) hybrid nanozyme (CuRuOX@HA) modified with hyaluronic acid (HA). Via hybridization, CuRuOX@HA NPs not only have good ROS generation capability but also possess excellent photothermal performance with a photothermal conversion efficiency of 62.7%. Thus, the CuRuOX@HA nanozyme achieves the synergistic treatment of drug-resistant bacterial infections using PTT/chemodynamic therapy (CDT). Moreover, under the mediated action of ROS, CuRuOX@HA can effectively deplete glutathione, which is a nutrient of bacteria, and hence, the nanozyme can impede the growth of drug-resistant bacteria. In vivo, this hybrid nanozyme efficiently removes MRSA from infected wounds and speeds up wound healing with few adverse effects. The CuRuOX@HA hybrid nanozyme is a viable candidate for clinical treatment due to its strong antibacterial activities and good biosafety.

Stanene nanosheets-based hydrogel for sonodynamic treatment of drug-resistant bacterial infection

Antibacterial resistance has caused a serious global threat to human health. It is essential to exploit a highly effective method for the treatment of drug-resistant bacterial infections. Herein, a sonodynamic antibacterial strategy based on stanene nanosheets (SnNSs) is developed. The obtained SnNSs have a classic nanosheet structure and exhibit excellent a high reactive oxygen species generation ability under ultrasound. Then, SnSNs are assembled with a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) to obtain Sn@hydrogel. Sn@hydrogel presents good sonodynamic antibacterial activity, thus improving the wound healing effect. The in vivo evaluation of full-layer methicillin-resistant staphylococcus aureus (MRSA) infected wound model shows that Sn@hydrogel has high anti-infection and wound healing effects. This stanene nanosheets-based hydrogel has good sonodynamic antibacterial effect, which provides a new way to effectively reduce bacterial infection and promote wound healing.

Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of −5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.