[New Drug Discovery Targeting Iron in Bacterial Infectious Diseases].

Iron is necessary for all living organisms, and bacteria that cause infections in human hosts also need ferrous ions for their growth and proliferation. In the human body, most ferric ions (Fe3+) are tightly bound to iron-binding proteins such as hemoglobin, transferrin, lactoferrin, and ferritin. Pathogenic bacteria express highly specific iron uptake systems, including siderophores and specific receptors. Most bacteria secrete siderophores, which are low-molecular weight metal-chelating agents, to capture Fe3+ outside cell. Siderophores are mainly classified as either catecholate or hydroxamate. Vibrio vulnificus, a Gram-negative pathogenic bacterium, is responsible for serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In our study, we generated deletion mutants of the genes encoding proteins involved in the vulnibactin mediated iron-utilization system, such as ferric-vulnibactin receptor protein (VuuA), periplasmic ferric-vulnibactin binding protein (FatB), ferric-vulnibactin reductase (VuuB), and isochorismate synthase (ICS). ICS and VuuA are required under low-iron conditions for ferric-utilization in M2799, but the alternative proteins FatB and VuuB can function as a periplasmic binding protein and a ferric-chelate reductase, respectively. VatD, which functions as ferric-hydroxamate siderophores periplasmic binding protein, was shown to participate in the ferric-vulnibactin uptake system in the absence of FatB. Furthermore, the ferric-hydroxamate siderophore reductase IutB was observed to participate in ferric-vulnibactin reduction in the absence of VuuB. We propose that ferric-siderophore periplasmic binding proteins and ferric-chelate reductases represent potential targets for drug discovery in the context of infectious diseases.

How to Mitigate Community Harms of Antibacterial Resistance With Patient-Centered Care.

Overprescription of antibiotics in cases in which bacterial infection is clinically uncertain contributes to increased prevalence of multidrug-resistant bacteria. Ethically, merits and drawbacks of stricter prescription practice oversight should be weighed against risks of untreatable bacterial infections to patients and communities. This article considers how to balance this set of ideas and values.

Association of multidrug-resistant bacteria and clinical outcomes in patients with infected diabetic foot in a Peruvian hospital: A retrospective cohort analysis.

OBJECTIVE: To evaluate the association of multidrug-resistant bacteria (MDRB) and adverse clinical outcomes in patients with diabetic foot infection (DFI) in a Peruvian hospital. MATERIALS AND METHODS: This retrospective cohort study evaluated patients treated in the Diabetic Foot Unit of a General Hospital in Lima, Peru. MDRB was defined by resistance to more than two pharmacological groups across six clinically significant genera. The primary outcome was death due to DFI complications and/or major amputation. Other outcomes included minor amputation, hospitalization, and a hospital stay longer than 14 days. Relative risks were estimated using Poisson regression for all outcomes. RESULTS: The study included 192 DFI patients with a mean age of 59.9 years; 74% were males. A total of 80.8% exhibited MDRB. The primary outcome had an incidence rate of 23.2% and 5.4% in patients with and without MDRB, respectively (p = 0.01). After adjusting for sex, age, bone involvement, severe infection, ischemia, diabetes duration, and glycosylated hemoglobin, MDRB showed no association with the primary outcome (RR 3.29; 95% CI, 0.77-13.9), but did with hospitalization longer than 14 days (RR 1.43; 95% CI, 1.04-1.98). CONCLUSIONS: Our study found no association between MDRB and increased mortality and/or major amputation due to DFI complications, but did find a correlation with prolonged hospitalization. The high proportion of MDRB could limit the demonstration of the relationship. It is urgent to apply continuous evaluation of bacterial resistance, implement a rational plan for antibiotic use, and maintain biosafety to confront this threat.

Development and validation of risk prediction model for bacterial infections in acute liver failure patients.

Infections significantly increase mortality in acute liver failure (ALF) patients, and there are no risk prediction models for early diagnosis and treatment of infections in ALF patients. This study aims to develop a risk prediction model for bacterial infections in ALF patients to guide rational antibiotic therapy. The data of ALF patients admitted to the Second Hospital of Hebei Medical University in China from January 2017 to January 2022 were retrospectively analyzed for training and internal validation. Patients were selected according to the updated 2011 American Association for the Study of Liver Diseases position paper on ALF. Serological indicators and model scores were collected within 24 h of admission. New models were developed using the multivariate logistic regression analysis. An optimal model was selected by receiver operating characteristic (ROC) analysis, Hosmer-Lemeshow test, the calibration curve, the Brier score, the bootstrap resampling, and the decision curve analysis. A nomogram was plotted to visualize the results. A total of 125 ALF patients were evaluated and 79 were included in the training set. The neutrophil-to-lymphocyte ratio and sequential organ failure assessment (SOFA) were integrated into the new model as independent predictive factors. The new SOFA-based model outperformed other models with an area under the ROC curve of 0.799 [95% confidence interval (CI): 0.652-0.926], the superior calibration and predictive performance in internal validation. High-risk individuals with a nomogram score ≥26 are recommended for antibiotic therapy. The new SOFA-based model demonstrates high accuracy and clinical utility in guiding antibiotic therapy in ALF patients.

In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis.

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Nature-Inspired Micro/Nano-Structured Antibacterial Surfaces.

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.

Revolutionizing healthcare: Harnessing nano biotechnology with zinc oxide nanoparticles to combat biofilm and bacterial infections-A short review.

A crucial pathogenic mechanism in many bacterial diseases is the ability to create biofilms. Biofilms are suspected to play a role in over 80 % of microbial illnesses in humans. In light of the critical requirement for efficient management of bacterial infections, researchers have explored alternative techniques for treating bacterial disorders. One of the most promising ways to address this issue is through the development of long-lasting coatings with antibacterial properties. In recent years, antibacterial treatments based on metallic nanoparticles (NPs) have emerged as an effective strategy in the fight over bacterial drug resistance. Zinc oxide nanoparticles (ZnO-NPs) are the basis of a new composite coating material. This article begins with a brief overview of the mechanisms that underlie bacterial resistance to antimicrobial drugs. A detailed examination of the properties of metallic nanoparticles (NPs) and their potential use as antibacterial drugs for curing drug-sensitive and resistant bacteria follows. Furthermore, we assess metal nanoparticles (NPs) as powerful agents to fight against antibiotic-resistant bacteria and the growth of biofilm, and we look into their potential toxicological effects for the development of future medicines.

Repurposing of drugs against bacterial infections: A pharmacovigilance-based data mining approach.

The World Health Organization (WHO) has published a list of priority pathogens that urgently require research to develop new antibiotics. The main aim of the current study is to identify potential marketed drugs that can be repurposed against bacterial infections. A pharmacovigilance-based drug repurposing approach was used to identify potential drugs. OpenVigil 2.1 tool was used to query the FDA Adverse Event Reporting System database. The reporting odds ratio (ROR) < 1, ROR95CI upper bound <1, and no. of cases ≥30 were used for filtering and sorting of drugs. Sunburst plot was used to represent drugs in a hierarchical order using the Anatomical Therapeutic Chemical classification. Molecular docking and dynamics were performed using the Maestro and Desmond modules of Schrodinger 2023 software respectively. A total of 40 drugs with different classes were identified based on the pharmacovigilance approach which has antibacterial potential. The molecular docking results have shown energetically favored binding conformation of lisinopril against 3-deoxy-manno-octulosonate cytidylyltransferase, UDP-2,3-diacylglucosamine hydrolase, and penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa; olmesartan, atorvastatin against lipoteichoic acids flippase LtaA and rosiglitazone and varenicline against  d-alanine ligase of Staphylococcus aureus; valsartan against peptidoglycan deacetylase (SpPgdA) and atorvastatin against CDP-activated ribitol for teichoic acid precursors of Streptococcus pneumoniae. Further, molecular dynamic results have shown the stability of identified drugs in the active site of bacterial targets except lisinopril with PBP3. Lisinopril, olmesartan, atorvastatin, rosiglitazone, varenicline, and valsartan have been identified as potential drugs for repurposing against bacterial infection.

Recent advances in cell membrane camouflaged nanotherapeutics for the treatment of bacterial infection.

Infectious diseases caused by bacterial infections are common in clinical practice. Cell membrane coating nanotechnology represents a pioneering approach for the delivery of therapeutic agents without being cleared by the immune system in the meantime. And the mechanism of infection treatment should be divided into two parts: suppression of pathogenic bacteria and suppression of excessive immune response. The membrane-coated nanoparticles exert anti-bacterial function by neutralizing exotoxins and endotoxins, and some other bacterial proteins. Inflammation, the second procedure of bacterial infection, can also be suppressed through targeting the inflamed site, neutralization of toxins, and the suppression of pro-inflammatory cytokines. And platelet membrane can affect the complement process to suppress inflammation. Membrane-coated nanoparticles treat bacterial infections through the combined action of membranes and nanoparticles, and diagnose by imaging, forming a theranostic system. Several strategies have been discovered to enhance the anti-bacterial/anti-inflammatory capability, such as synthesizing the material through electroporation, pretreating with the corresponding pathogen, membrane hybridization, or incorporating with genetic modification, lipid insertion, and click chemistry. Here we aim to provide a comprehensive overview of the current knowledge regarding the application of membrane-coated nanoparticles in preventing bacterial infections as well as addressing existing uncertainties and misconceptions.

Bacterial profile, drug resistance pattern, clinical and laboratory predictors of ascites infection in cirrhosis patients.

Ascites is a pathological collection of free fluid in the peritoneal cavity, which is a common complication in patients with cirrhosis, an advanced liver disease. Bacterial infection increases the mortality rate of hospitalized patients with cirrhosis, irrespective of the severity of the liver disease. Around 60% of patients with compensated cirrhosis developed ascites within 10 years during the course of their disease. The in-hospital mortality rate due to spontaneous bacterial peritonitis (SBP) could exceed 90%, but with early diagnosis and prompt antibiotic therapy, this rate has been shown to decrease to 20%. Here, we enrolled adult (age ≥ 18) patients with liver disease with evidence of cirrhosis who developed ascites and assessed the presence of spontaneous ascites fluid infection (SAFI) in these patients. Of the total 218 patients, 22.9% (50/218) develop ascites infection. The liver organ function tests like alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin were found to be significantly (P < 0.05) higher in patients with ascites fluid infection compared to patients with non-ascites fluid infection. Of the gram-negative bacteria, K. pneumonia and E. coli were isolated and found to be 100% resistant to amoxicillin and clavulanate. From the gram-positive bacterial isolates, S. aureus was only resistant to penicillin, whereas Str. viridans was resistant to ceftriaxone, cefotaxime, cefepime, and penicillin. On the other hand, clinical features such as a history of jaundice, low arterial blood pressure, and ultrasound results such as a shrunken liver and enlarged spleen were also independent predictors of spontaneous bacterial peritonitis. In conclusion, given the high probability of death following SAFI, early detection, and treatment, as well as knowledge of the microbial agent, resistance profile, and predictive markers in various contexts, are essential for the timely diagnosis and management of SAFI in these patients.

Microbial extracellular vesicles contribute to antimicrobial resistance.

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

BACKGROUND: Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. METHODS: We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. RESULTS: Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. CONCLUSIONS: We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.

Impact of inadequate empirical antibiotic treatment on outcome of non-critically ill children with bacterial infections.

BACKGROUND: The impact of inadequate empirical antibiotic treatment on patient outcomes and hospitalization duration for non-life-threatening infections in children remains poorly understood. We aimed to assess the effects of inadequate empirical antibiotic treatment on these factors in pediatric patients. METHODS: The medical records of children admitted for infectious diseases with bacteria isolated from sterile sites between 2018 and 2020 were retrospectively reviewed. Patients who received adequate empirical treatment were compared with those who received inadequate treatment in terms of demographic, clinical, and laboratory variables. RESULTS: Forty-eight patients who received inadequate empirical antimicrobial treatment were compared to 143 patients who received adequate empirical treatment. Inadequate empirical antimicrobial treatment did not significantly affect the length of hospital stay or the incidence of complications in non-critically ill children with bacterial infections. Younger age and underlying renal abnormalities were identified as risk factors for inadequate antimicrobial treatment, while associated bacteremia was more common in the adequate antimicrobial treatment group. CONCLUSIONS: inadequate antibiotic treatment did not affect the outcomes of non-critically ill children with bacterial infectious diseases. Therefore, routine empirical broad-spectrum treatment may not be necessary for these cases, as it can lead to additional costs and contribute to antibiotic resistance. Larger prospective studies are needed to confirm these findings.

Bullet-related bacterial wound infections among injured personnel at emergency site hospitals in Bahir Dar: prevalence, antimicrobial susceptibility and associated factors.

BACKGROUND: Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause severe wound infections, persistent systemic infections and may lead to amputation and mortality. The magnitude, antimicrobial susceptibility profiles, and factors associated with bacterial wound infections among patients with bullet-related injuries are not yet studied particularly at health facilities in Bahir Dar, Northwest Ethiopia. Therefore, this study was aimed to determine the prevalence, bacterial profiles, antimicrobial susceptibility profiles, and factors associated with bacterial infections among patients with bullet-related injuries at referral health facilities in Bahir Dar, Northwest Ethiopia. METHODS: A Hospital-based cross-sectional study was conducted among patients with bullet-related injuries at three referral health facilities in Bahir Dar from May 25 to July 27, 2022. A total of 384 patients with bullet-related injuries were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Wound swabs were collected aseptically and cultured on Blood and MacConkey agar following bacteriological standards. Biochemical tests were performed to differentiate bacteria for positive cultivation and antimicrobial susceptibility profiles of the isolates were done on Muller Hinton agar using the Kirby-Bauer disk diffusion technique according to the 2021 Clinical Laboratory Standard Institute (CLSI) guideline. The data were entered using Epi-Info version 7.3 and analyzed using SPSS version 25. Descriptive data were presented using frequency, percentages, figures, and charts. Logistic regression was carried out to identify factors associated with bacterial wound infections. P-value < 0.05 was considered statistically significant. RESULTS: The prevalence of bullet-related bacterial wound infection among three referral hospitals in Bahir Dar city was 54.7%. The most commonly isolated Gram-negative organism was Klebsiella spps 49 (23.3%) while among Gram-positive organism, Staphylococcus aureus 58 (27.6%) and coagulase-negative staphylococci (CONS) 18 (8.6%). Contamination, hospitalization and smoking habit were significantly associated with the presence of bullet-related bacterial wound infections. Over 97% multidrug resistant (MDR) bacterial isolates were identified and of theses, E. coli, Proteus species, Citrobactor, and Staphylococcus aureus were highly drug resistant. CONCLUSION: Increased prevalence of bullet-related bacterial wound infection was noticed in this study. S. aureus followed by Klebsiella species were most commonly isolated bacteria. High frequency of resistance to Ampicillin, Oxacillin, Cefepime, Ceftriaxone, Ceftazidime, Vancomycin, and Norfloxacin was observed. Therefore, proper handling of bullet injuries, prompt investigation of bacterial infections, monitoring of drug sensitivity patterns and antibiotic usage are critical.

Decoding antimicrobial resistance: unraveling molecular mechanisms and targeted strategies.

Antimicrobial resistance poses a significant global health threat, necessitating innovative approaches for combatting it. This review explores various mechanisms of antimicrobial resistance observed in various strains of bacteria. We examine various strategies, including antimicrobial peptides (AMPs), novel antimicrobial materials, drug delivery systems, vaccines, antibody therapies, and non-traditional antibiotic treatments. Through a comprehensive literature review, the efficacy and challenges of these strategies are evaluated. Findings reveal the potential of AMPs in combating resistance due to their unique mechanisms and lower propensity for resistance development. Additionally, novel drug delivery systems, such as nanoparticles, show promise in enhancing antibiotic efficacy and overcoming resistance mechanisms. Vaccines and antibody therapies offer preventive measures, although challenges exist in their development. Non-traditional antibiotic treatments, including CRISPR-Cas systems, present alternative approaches to combat resistance. Overall, this review underscores the importance of multifaceted strategies and coordinated global efforts to address antimicrobial resistance effectively.

Impact of lumacaftor/ivacaftor on the bacterial and fungal respiratory pathogens in cystic fibrosis: a prospective multicenter cohort study in Sweden.

BACKGROUND: A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden. OBJECTIVES: The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden. DESIGN: The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor. METHODS: Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed. RESULTS: Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive. CONCLUSION: The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.

Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance.

Antimicrobial resistance (AMR) is one of the most critical threats to global public health in the 21st century, causing a large number of deaths every year in both high-income and low- and middle-income countries. Vaccines and monoclonal antibodies can be exploited to prevent and treat diseases caused by AMR pathogens, thereby reducing antibiotic use and decreasing selective pressure that favors the emergence of resistant strains. Here, differences in the mechanism of action and resistance of vaccines and monoclonal antibodies compared to antibiotics are discussed. The state of the art for vaccine technologies and monoclonal antibodies are reviewed, with a particular focus on approaches validated in clinical studies. By underscoring the scope and limitations of the different emerging technologies, this review points out the complementary of vaccines and monoclonal antibodies in fighting AMR. Gaps in antigen discovery for some pathogens, as well as challenges associated with the clinical development of these therapies against AMR pathogens, are highlighted.

The scope of the antimicrobial resistance challenge.

Each year, an estimated 7·7 million deaths are attributed to bacterial infections, of which 4.95 million are associated with drug-resistant pathogens, and 1·27 million are caused by bacterial pathogens resistant to the antibiotics available. Access to effective antibiotics when indicated prolongs life, reduces disability, reduces health-care expenses, and enables access to other life-saving medical innovations. Antimicrobial resistance undoes these benefits and is a major barrier to attainment of the Sustainable Development Goals, including targets for newborn survival, progress on healthy ageing, and alleviation of poverty. Adverse consequences from antimicrobial resistance are seen across the human life course in both health-care-associated and community-associated infections, as well as in animals and the food chain. The small set of effective antibiotics has narrowed, especially in resource-poor settings, and people who are very young, very old, and severely ill are particularly susceptible to resistant infections. This paper, the first in a Series on the challenge of antimicrobial resistance, considers the global scope of the problem and how it should be measured. Robust and actionable data are needed to drive changes and inform effective interventions to contain resistance. Surveillance must cover all geographical regions, minimise biases towards hospital-derived data, and include non-human niches.

Fighting bacteria with bacteria: A biocompatible living hydrogel patch for combating bacterial infections and promoting wound healing.

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.