Improving treatment plan and mental health in children with abdominal infection for broad-spectrum bacterial infections

BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment.In surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects.AIM To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy.METHODS A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped.The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the operation.RESULTS White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(P<0.05).The hospital stay in the observation group was significantly shorter than that in the control group.The hospitalization cost in the observation group was significantly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics,improving treatment outcomes and reducing medical costs to some extent.

Multi Drug Resistance Bacterial Isolates of Surgical Site Infection

Multi drug resistance microorganism is considered to be one of the major health problems. The aim of this study was to determine antibiotic susceptibility pattern of bacterial pathogens of surgical site infection. A total 250 samples were included, out of which 62.4% showed significant bacterial growth. Gram negative bacteria were 85.25% and gram positive bacteria were 14.75%;among them 65.38% of the total isolates were multi drug resistance (MDR). The age group between 31 - 40 found the highest number of isolates 22.4%. Among gram negative bacilli, the highest production of MDR was found in Acinetobacter spp. followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. In gram positive cocci, the highest production of MDR was found in Staphylococcus aureus. Acinetobacter spp. was found highly susceptible to amikacin and gentamycin 20.1% followed by ofloxacin and ciprofloxacin 18.6% and 16.2% respectively. Staphylococcus aureus showed 100% sensitive to clindamycin whereas penicillin showed 100% resistance followed by amoxycillin (93.75%). Amikacine and clindamycin were drugs of choice for gram negative and gram positive bacteria respectively. This study showed that alarming increase of infections was caused by multi drug resistance bacterial organisms. It increases length of stay and may produce lasting sequelae and requires extra resources for investigations, management and nursing care. Surveillance of surgical site infection is a useful tool to demonstrate the magnitude of the problem and find out appropriate preventive methods.

<i>In-Vitro</i>Inhibitory Effect of Methanol Extracts of Chinese Herbal Drugs on Supercoiling Activity of Bacterial DNA Gyrase

A large number of Chinese herbal drugs (CHDs) exhibit antibacterial activities both in vivo and in vitro, but until now little is known regarding their inhibitory mechanisms. Bacterial DNA gyrase is a proven target for antibacterial agents. Aim of this study was to investigate the in-vitro inhibitory effect of methanol extracts of CHDs against supercoiling activity of bacterial DNA gyrase. Fifteen CHDs were selected and extracted with methanol, respectively. Inhibitory effect of the extracts on DNA gyrase was tested using gel-based DNA supercoiling assay. Among fifteen CHDs tested, methanol extracts of Lonicerae Japonicae Flos (S2), Taraxaci Herba (S7), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (S8) demonstrated an obvious inhibitory effect against supercoiling activity of DNA gyrase, and the others were either less active or could not be determined with the present method. Moreover, it was likely that S7 and S8 inhibit gyrase in a concentration-dependent manner. In conclusion, DNA supercoiling assay is a promising method to study the inhibitory activity of CHDs on bacterial DNA gyrase. Some CHDs do have gyrase-inhibitory activity as proposed. Further investigations are needed to elucidate the inhibition mechanism of these CHDs on supercoiling activity of gyrase.

Bacterial contamination of orally-consumed crude herbal remedies:A potential source for multi-drug resistant pathogens in man

Objective:The acceptability of herbal remedies for alleviating discomforts and ill-health has become very popular, on the account of the increasing cost of allopathic medicine for personal health maintenance.The observable non-adherence of herbalists to the established World Health Organization(WHO) / National Agency for Food and Drug Administration Control(NAFDAC) regulations for the quality control of herbal medicines is an issue for concern.In view of this,34 popular and widely consumed crude herbal remedies in southwestern,Nigeria were screened for compliance with standard limits for bacterial contamination,bacteria flora and their antibiotic susceptibility pattern.Methods:Isolates recovered from samples were identified using the cultural, morphological and biochemical characteristics.They were also tested for drug sensitivity using standard procedures. Results:A heavy bacteria load ranging from 3.00×10~3-9.58×10~5 CFU/ML and 1.20×10~5- 5.41×10~5 CFU/ML was observed for water and spirit extracted preparations respectively.The bacteria flora cum contaminants were:Staphylococcus aureus,Bacillus cereus,Bacillus subtilis,Pseudomonas aeruginosa, Micrococcus luteus,Lactobacillus plantarum,Klebsiella pneumoniae,Escherichia coli,streptococcus,Shigella, Neisseria,Arthrobacter,Kurthia and Clostridium species.All the isolates were multi-drug resistant(MDR) strains.Conclusion:The crude herbal preparations consumed in Nigeria failed to comply with the internationally recognized standards regarding bacteria load and flora.The presence of MDR pathogens is of greatest concern. It poses a great risk to consumers health and could be a source of introducing MDR organisms into the human population.There is the need for the enforcement of established guidelines to ensure the safety of these preparations.

New determinants of prognosis in bacterial infections in cirrhosis

Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and mortality.Bacterial infections are one of the main causes of decompensation.It is very important for clinical management to be aware of the population with the highest risk of poor outcome.This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently.Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines.Moreover,it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and,in infected patients,with the degree of sepsis.It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection,severe sepsis,hepatorenal syndrome and death.We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis(SBP) is the most common infection in end-stage liver disease patients.SBP is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm^3 without an evident intra-abdominal surgically treatable source.Several mechanisms contribute to SBP occurrence,including translocation of gut bacteria and their products,reduced intestinal motility provoking bacterial overgrowth,alteration of the gut's barrier function and local immune responses.Historically,Gram-negative enteric bacteria have been the main causative agents of SBP,thereby guiding the empirical therapeutic choice.However,over the last decade,a worryingly increasing prevalence of Gram-positive and multi-drug resistant(MDR) SBP has been seen.Recently,the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria(48%-62%).The overall proportion of MDR bacteria is up to 22%-73% of cases.Consequently,empirical therapy based on thirdgeneration cephalosporins or amoxicillin/clavulanic acid,can no longer be considered the standard of care,as these drugs are associated with poor outcomes.Theaim of this review is to describe,with an epidemiological focus,the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present,and illustrate potential targeted therapeutic strategies.An appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem,with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.

Antibiotic sensitivity pattern of common bacterial pathogens in NICU and neonatal ward in Hamedan province of Iran

Bacterial pathogens and drug resistance are different in hospitals of each country. In this study we determined bacterial path- ogens and drug sensitivity in the neonatal ward and neonatal intensive care unit (NICU) in Ekbatan hospital in Hamedan. This cross-sectional descriptive study was done on 1150 hospitalized neonates in neonatal and NICU wards of Ekbatan hospital of the Hamadan university of medical sciences from September 2004 to September 2006. Blood, cerebrospinal fluid (CSF), urine, stool, eye excretion, synovial fluid, umbilical secretion and ascitic fluid were evaluated. Positive cultures were evaluated for antibiotic resistance with disk diffusion test methed. All of the data in questionnaires was analyzed with SPSS 13. Cultures including blood, urine, CSF , stool, eye excretion, synovial fluid, umbilical secretion and ascitic fluid was done in 417 neonates (833 cultures). These cultures were including: urine, 323 cases (38.8%) blood 293 cases (35.2%), CSF 180 cases (21.6%) , stool 17 cases (2%), eye secretion 16 cases (1.9%) and other secretions (synovial, umbilical, etc) 4 cases (0.5%). The cultures were positive in 105 cases (25.2%). 60 male neonates (57.1%) and 45 female neonates (42.9%) were culture positive. The most common microorganisms were E coli 66.7% (70 cases), Klebsiella 10.5% (11 cases). Drug resistance was high in these microorganisms. The most common microorganisms were Ecoli and klebsiella. Drug resistance was high in the isolated microorganisms.

Nanopores Structure in Electrospun Bacterial Cellulose

Bacterial cellulose (BC) has established to be a remarkably versatile biomaterial and can be used in wide variety of applied scientific endeavours, especially for medical devices, lately, bacterial cellulose mats are used in the treatment of skin conditions such as burns and ulcers, because of the morphology of fibrous biopolymers serving as a support for cell proliferation, its pores allow gas exchange between the organism and the environment. Moreover, the nanostructure and morphological similarities with collagen make BC attractive for cell immobilization and cell support. In this work, we obtain first electrospun bacterial cellulose mats after chemical treatment and without conductive additives. With DMA/LiClmechanism dissolution, modified bacterial cellulose was easily electrospun in chloroform/acetone solvents in comparison with BC unmodified. FTIR peaks results are consistent with proposed interactions between cellulose and DMA/LiCl solvent system.

Six-year analysis of key monitoring for bacterial strain distribution and antibiotic sensitivity in a hospital

BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice.AIM To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by clinicians.METHODS Specimens from across the institution were collected by the microbiology laboratory.The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical analysis.RESULTS A total of 12062 bacterial strains of key monitoring significance were detected.Staphylococcus aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or linezolid.Moreover,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected.Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was low.Enterococcus faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus faecalis.The resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem.The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years.The resistance to amikacin remained at 0.2%over the past 3 years.CONCLUSION Our hospital’s overall antibiotic resistance rate was relatively stable from 2017 to 2022.The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital,which can guide clinical antibiotic selection.

Unresolved issues in the prophylaxis of bacterial infections in patients with cirrhosis

Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant bacteria.Currently, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A singlecenter study

AIM To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation(LDLT) in cirrhotic patients.METHODS This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra-and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS Thirty-three patients(73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection(28.6% and 27.8%, respectively). The most common isolated organisms were gramnegative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes(19% and 33.3%, respectively), followed by Escherichia coli for repeated infections(11.1%), and Pseudomonas aeruginosa for single infections(19%). Levofloxacin showed high sensitivity against repeated infection episodes(P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant(MDR). Pre-transplant hepatocellular carcinoma(HCC) and duration of drain insertion(in days) were independent risk factors for the occurrence of repeated infection episodes(P = 0.024).CONCLUSION MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.

A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

Bacterial extracellular vesicles as bioactive nanocarriers for drug delivery:Advances and perspectives

Nanosized extracellular vesicles derived from bacteria contain diverse cargo and transfer intercellular bioactive molecules to cells.Due to their favorable intercellular interactions,cell membrane-derived bacterial extracellular vesicles(BEVs)have great potential to become novel drug delivery platforms.In this review,we summarize the biogenesis mechanism and compositions of various BEVs.In addition,an overview of effective isolation and purification techniques of BEVs is provided.In particular,we focus on the application of BEVs as bioactive nanocarriers for drug delivery.Finally,we summarize the advances and challenges of BEVs after providing a comprehensive discussion in each section.We believe that a deeper understanding of BEVs will open new avenues for their exploitation in drug delivery applications.

Study on Anti-diarrhea Effect of the Prescription of 4 Tibetan Veterinary Drugs

This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata （ Benth. ） Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups （0. 060, 0. 030 and 0. 020 g/ml, respectively）. The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs （high dose, 0.06 g/ml） exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.

A new track for antibacterial treatment:Progress and challenges of using cytomembrane-based vesicles to combat bacteria

The emergence and re-emergence of antibiotic-resistant bacteria,especially superbugs,are leading to complicated infections that are increasingly difficult to treat.Therefore,novel alternative antimicrobial therapies are urgently needed to reduce the morbidity and mortality caused by antibiotic resistance.The development of biomimetic-based therapy is expected to provide innovative means for addressing this challenging task.As a kind of novel biomaterial,cytomembrane-based vesicles(MVs)continue to receive considerable attention in antimicrobial therapy owing to their inherent biocompatibility,design flexi-bility,and remarkable ability to interact with biological molecules or the surrounding environment.These remarkable cell-like properties and their inherent interaction with pathogens,toxins,and the immune system underlie MVs-based functional protein therapy and targeted delivery to develop advanced therapeutic strategies against bacterial infection.This review provides a fundamental under-standing of the characteristics and physiological functions of cytomembrane-based vesicles,focusing on their potential to combat bacterial infections,including detoxification,immune modulation,antibiotics delivery,and physical therapy.In addition,the future possibilities and remaining challenges for clinically implementing MVs in the field of antibacterial treatment are discussed.

Virus-inspired nanoparticles as versatile antibacterial carriers for antibiotic delivery against Gram-negative and Gram-positive bacteria

Infectious diseases become one of the leading causes of human death. Traditional treatment based on classical antibiotics could not provide enough antibacterial activity to combat bacterial infections due to low bioavailability, even leading to antibiotic resistance. In recent years, biomimetic delivery systems have been developed to improve drug therapy for various diseases, such as malignant tumor and cardiovascular disease. In this work, we designed virus-inspired nanodrugs(VNDs) through co-assembly of amphiphilic lipopeptide dendrons and poly(lactic-co-glycolic acid) polymers for high-efficiency antibiotic delivery. These VNDs had well-defined and stable nanostructures for tetracycline encapsulation and delivery. The VNDs were capable of promoting antibiotic internalization and enhancing their antibacterial effects against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Additionally, no obvious cytotoxicity of VNDs was observed to human cell lines. This work successfully demonstrated the virus-mimetic nanoparticles served as promising and applicable antibiotic delivery platform for antibacterial treatment.

Detection of bacterial endotoxin in paclitaxel liposome

Based on current research, there are three technologies during the test of bacterial endotoxin of liposomes：（1） extraction of bacterial endotoxin from liposomes;（2） addition of bacterial endotoxin in the process of recovery test; and（3） elimination of the interference factors from drugs and excipients. In the present study, we pointed out that the key technologies to test bacterial endotoxin from paclitaxel liposome included following steps： extraction of bacterial endotoxins from ethanol-dissolved liposomes; preparation of positive control of recovery solution by adding 0.01 m L standard endotoxins in 1 m L liposome ethanol solution; and the use of 0.5% human albumin to eliminate the interference from detection, and accurate detection of the bacterial endotoxin of liposomes.

Distribution and drug resistance of pathogens in burn patients in China from 2006 to 2019

BACKGROUND In this study,recent trends in the distribution and drug resistance of pathogenic bacteria isolated from patients treated at a burn ward between 2006 and 2019 were investigated.AIM To develop more effective clinical strategies and techniques for the prevention and treatment of bacterial infections in burn patients.METHODS Clinical samples with positive bacteria were collected from patients at the burn ward in Beijing Jishuitan Hospital in China between January 2006 and December 2019.The samples were retrospectively analyzed,the distribution of pathogenic bacteria was determined,and the trends and changes in bacterial drug resistance during different period were assessed.Drug resistance in several main pathogenic bacteria from 2006 to 2011 and from 2012 to 2019 was comparatively summarized and analyzed.RESULTS Samples from 17119 patients were collected and analyzed from 2006 to 2019.Surprisingly,a total of 7960 strains of different pathogenic bacteria were isolated at this hospital.Among these bacteria,87.98%(7003/7960)of the strains were isolated from burn wounds,and only 1.34%(107/7960)were isolated from the blood of patients.In addition,49.70%(3956/7960)were identified as Grampositive bacteria,48.13%(3831/7960)were Gram-negative bacteria,and the remaining 2.17%(173/7960)were classified as fungi or other pathogens.Importantly,Staphylococcus aureus(21.68%),Pseudomonas aeruginosa(14.23%),and Staphylococcus epidermidis (9.61%) were the top three pathogens most frequentlyisolated from patients.CONCLUSION In patients treated at the burn ward in this hospital from 2006 to 2019,Staphylococcus aureus and Pseudomonas aeruginosa were the predominant clinicalpathogens responsible for bacterial infections. The circumstantial detection anddetailed monitoring of the intensity and growth of different pathogenic bacteria inclinical patients as well as tests of drug sensitivity during burn recovery areparticularly important to provide guidelines for the application of antibiotics andother related drugs. Careful collection and correct, standard culture of bacterialspecimens are also crucial to improve the efficiency of bacterial infectiondetection. Effective monitoring and timely clinical treatment in patients may helpreduce the possibility and rate of infection as well as alleviate the effects of drugresistance among patients in burn centers.

Bacterial outer membrane vesicles-based therapeutic platform eradicates triple-negative breast tumor by combinational photodynamic/chemo-/immunotherapy

Bacterial outer membrane vesicles(OMVs)are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine.In this study,OMVs are demonstrated as promising antitumor therapeutics.OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity,but the therapeutic window of OMVs is narrow for its toxicity.We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6(Ce6)and chemotherapeutic drug doxorubicin(DOX)into OMVs as a therapeutic platform.We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform,providing combinational photodynamic/chemo-/immunotherapy,eradicates triple-negative breast tumors in mice without side effects.Importantly,this strategy also effectively prevents tumor metastasis to the lung.This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

Recent advances in bacterial therapeutics based on sense and response

Intelligent drug delivery is a promising strategy for cancer therapies.In recent years,with the rapid development of synthetic biology,some properties of bacteria,such as gene operability,excellent tumor colonization ability,and host-independent structure,make them ideal intelligent drug carriers and have attracted extensive attention.By implanting condition-responsive elements or gene circuits into bacteria,they can synthesize or release drugs by sensing stimuli.Therefore,compared with traditional drug delivery,the usage of bacteria for drug loading has better targeting ability and controllability,and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs.This review mainly introduces the development of bacterial-based drug delivery carriers,including mechanisms of bacterial targeting to tumor colonization,gene deletions or mutations,environment-responsive elements,and gene circuits.Meanwhile,we summarize the challenges and prospects faced by bacteria in clinical research,and hope to provide ideas for clinical translation.