Development Of Bacterial Resistance Research Articles

Miniature Robots for Battling Bacterial Infection.

Micro/nanorobots have shown great promise for minimally invasive bacterial infection therapy. However, bacterial infections usually form biofilms inside the body by aggregation and adhesion, preventing antibiotic penetration and increasing the likelihood of recurrence. Moreover, a substantial portion of the infection happens in those hard-to-access regions, making delivery of antibiotics to infected sites or tissues difficult and exacerbating the challenge of addressing bacterial infections. Micro/nanorobots feature exceptional mobility and controllability, are able to deliver drugs to specific sites (targeted delivery), and enhance drug penetration. In particular, the emergence of bioinspired microrobot surface design strategies have provided effective alternatives for treating infections, thereby preventing the possible development of bacterial resistance. In this paper, we review the recent advances in design, mechanism, and actuation modalities of micro/nanorobots with exceptional antimicrobial features, highlighting active therapy strategies for bacterial infections and derived complications at various organs, from the laboratory bench to in vivo applications. The current challenges and future research directions in this field are summarized. Those breakthroughs in micro/nanorobots offer a huge potential for clinical translation for bacterial infection therapy.

Wide‐Spectrum Nano‐Antibiotics Based on TPA‐Py@AuNCs⊂BSA for Multimodal Synergistic Therapy of Drug‐Resistant Bacteria and Wound Infections

ABSTRACTTo meet the high requirements of biomedical applications in antimicrobial agents, it is crucial to explore efficient nano‐antimicrobial agents with no resistance and good biocompatibility for treating infected wounds. In this study, composite nano‐antibiotic TPA‐Py@AuNCs⊂BSA nanoparticles (TAB NPs) are prepared using hollow mesoporous Au nanocages (AuNCs) loaded with a photosensitizer (namely TPA‐Py) with D‐π‐A structure showing aggregation‐induced emission properties. When TPA‐Py is encapsulated in the cavity of AuNCs, its fluorescence is suppressed. In the presence of photothermal induction, TPA‐Py can be released from the AuNCs, allowing for the restoration of fluorescence illumination and the specific imaging of Gram‐positive bacteria. TAB NPs demonstrate outstanding antimicrobial activity against a variety of bacteria, and this multimodal antimicrobial property does not lead to the development of bacterial resistance. In vitro experiments show that TAB NPs could eliminate bacteria and ablate bacterial biofilm. In vivo experiments show that the synergistic antimicrobial effect of TAB NPs has a significant positive impact on the treatment of infected wounds, including rapid antibacterial action, promotion of M2 macrophage polarization, and enhancement of chronic wound healing. This study provides an effective strategy for developing wide‐spectrum nano‐antibiotics for the ablation of bacterial biofilms and the treatment of infected wounds.

Comparative evaluation of chlorhexidine gluconate with alcohol and polyhexamethylene biguanide with Tris-EDTA as antiseptic solutions for pre-operative skin preparation in dogs

Background and Aim: Skin antisepsis plays a crucial role in pre-operative skin preparation, with chlorhexidine gluconate and alcohol being historically the preferred choice. However, concerns have risen regarding the development of bacterial resistance to chlorhexidine. Polyhexamethylene biguanide (PHMB) combined with Tris-ethylenediaminetetraacetic acid (Tris-EDTA) has recently emerged as a skin and wound antiseptic. This study aimed to compare the antibacterial efficacy and local safety of 2% chlorhexidine gluconate with 70% alcohol (CG+Alc) and 0.3% PHMB with 6% Tris and 1.86% EDTA (PHMB+Tris-EDTA) for pre-operative skin preparation in dogs. Materials and Methods: Twenty-four adult dogs underwent aseptic preparation on both sides of their ventral abdomens, with one side receiving CG+Alc and the other side receiving PHMB+Tris-EDTA, assigned randomly. Skin swab samples were collected pre-antisepsis and at 3-, 10-, and 60-min post-antisepsis to quantify bacterial colony-forming units (CFUs). Local skin reactions (erythema and edema) were evaluated after hair clipping, pre-antisepsis, and at 3-, 10-, 30-, and 60-min post-antisepsis. Results: There was no significant difference in bacterial CFU counts between the two antiseptic groups pre-antiseptic. Both solutions significantly reduced CFU counts (p < 0.05) at all post-antisepsis sampling times compared with pre-antisepsis. However, dogs treated with PHMB+Tris-EDTA showed a significantly higher incidence of edema at 10 min (p = 0.02) and 30 min (p = 0.003) and a higher incidence of erythema at 10 min (p = 0.043) post-antisepsis compared with CG+Alc. No skin reactions were observed in either group at 60 min post-antisepsis. Conclusion: CG+Alc and PHMB+Tris-EDTA reduced bacterial counts in pre-operative skin preparation in dogs. However, acute transient skin reactions were observed more frequently following the application of PHMB+Tris-EDTA. Keywords: alcohol, antisepsis, chlorhexidine gluconate, dogs, polyhexamethylene biguanide, skin preparation, tris-ethylenediaminetetraacetic acid.

Nano Revolution: Harnessing Nanoparticles to Combat Antibiotic-resistant Bacterial Infections.

Nanoparticles, defined as particles ranging from 1 to 100 nanometers in size, are revolutionizing the approach to combating bacterial infections amid a backdrop of escalating antibiotic resistance. Bacterial infections remain a formidable global health challenge, causing millions of deaths annually and encompassing a spectrum from common illnesses like Strep throat to severe diseases such as tuberculosis and pneumonia. The misuse of antibiotics has precipitated the rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and carbapenem-resistant Enterobacteriaceae (CRE), underscoring the critical need for innovative therapeutic strategies. Nanotechnology offers a promising avenue in this crisis. Nanoparticles possess unique physical and chemical properties that distinguish them from traditional antibiotics. Their high surface area to volume ratio, ability to be functionalized with various molecules, and distinctive optical, electronic, and magnetic characteristics enable them to exert potent antibacterial effects. Mechanisms include physical disruption of bacterial membranes, generation of Reactive Oxygen Species (ROS), and release of metal ions that disrupt bacterial metabolism. Moreover, nanoparticles penetrate biofilms and bacterial cell walls more effectively than conventional antibiotics and can be precisely targeted to minimize off-target effects. Crucially, nanoparticles mitigate the development of bacterial resistance by leveraging multiple simultaneous mechanisms of action, which make it challenging for bacteria to adapt through single genetic mutations. As research advances, nanotechnology holds immense promise in transforming antibacterial treatments, offering effective solutions that address current infections and combat antibiotic resistance globally. This review provides a comprehensive overview of nanoparticle applications in antibacterial therapies, highlighting their mechanisms, advantages over antibiotics, and future directions in healthcare innovation.

Anti-quorum sensing activity of essential oils against multidrug-resistant Klebsiella pneumoniae: a novel approach to control bacterial virulence.

The increasing resistance of microbes to conventional drugs is a serious problem worldwide that has increased the need for alternative antimicrobial compounds. Naturally occurring essential oils (EOs) are considered an important component of traditional pharmacopeia because of their antimicrobial and antioxidant properties. This has attracted researchers to identify novel therapeutic anti-pathogenic agents that could act as non-toxic quorum sensing inhibitors, thus controlling infections without encouraging the development of bacterial resistance. This prompted to undertake the current investigation to unravel the efficacy of EOs as QS modulators in reducing the virulence of multidrug resistant (MDR) strains ofKlebsiella pneumoniae. The study highlighted the anti-QS activity of fifteen EOs in modulating the QS-related traits by a reduction in capsular polysaccharide, exopolysaccharide and siderophore production in addition to inhibition of biofilm formation. The overall results suggest using EOs to develop alternate intervention strategies to mitigate infections caused by MDR strains ofK. pneumoniae.

Statistical Design and Analysis for Enhanced Production of Tetracycline‐Conjugated Copper Oxide Nanoparticles with Improved Antimicrobial Properties

AbstractPurpose: Since decades, numerous antibiotics have been used to treat different bacterial illnesses; among these, tetracycline is one of the commonly used antibiotics, which has led to development of bacterial resistance. To tackle this critical issue, we have developed a novel, biocompatible nanodrug that improves the antibacterial activity of tetracycline by conjugating it with copper oxide nanoparticles, thereby addressing the problem of multidrug resistance in bacteria. Methods: In this study, using unipot approach, tetracycline conjugated copper oxide nanoparticles were synthesized where tetracycline act as reducing as well as stabilizing agent. These nanoparticles were characterized by different analytical and microscopic technique. For statistical analysis, FFD and CCD model were employed to assess the effect of various parameters (concentration, pH, temperature and time). Results: The synthesis of nanoparticles was confirmed through different techniques. Synthesized nanoparticles exhibited the highest antibacterial activity against various microbes including multi‐drug resistant microbes compared to its individual constituents. DPPH and ABTS assays revealed high antioxidant activity of nanoparticles whereas, biocompatibility was assessed via MTT assay. The drug release profile confirms the sustained release of tetracycline molecules. Conclusions: We have successfully developed tetracycline conjugated copper oxide nanoparticles exhibiting potent antibacterial, antioxidant and biocompatible activity.

Development of bacterial resistance in Germany from 2008 to 2022 - major culprit pathogens, antibacterial drugs, and prescribing practices.

Rising bacterial resistance is a global threat, causing rising financial burdens on healthcare systems and endangering effective treatment of bacterial infections. To ensure the efficacy of antibacterial drugs, it is essential to identify the most dangerous pathogens and vulnerable antibacterial drugs. Previous research by our group suggested irrational outpatient prescribing practices in Germany, supporting a growing bacterial resistance. This study analyses developments and characteristics for the ten most prescribed antibacterial drugs in Germany from 2008 to 2022. Conclusions are based on the development of bacterial resistance levels and an analysis of correlations between pathogens. We identified cefuroxime axetil, sulfamethoxazole-trimethoprim and nitrofurantoin as the most problematic drugs. Particularly problematic pathogens include E. faecalis, E. faecium, K. pneumoniae, and P. mirabilis. Besides increasing bacterial resistance, they are characterised by a high proportion of significant positive correlations, indicating a high potential for mutually reinforcing resistance development. Alarmingly, most of the antibacterial drugs analysed showed a growing resistance to at least one of the analysed pathogens. In most cases, the best treatment option is threatened by increasing bacterial resistance. We also identified several differences between current bacterial resistance data and therapeutic guidelines. In aggregate, our findings support irrational prescribing behaviour and underscore the urgent need for improved prescribing practices to counter rising bacterial resistance in Germany. Moreover, therapeutic guidelines for bacterial infections, the "holy grail" of pharmacotherapy, must be updated more frequently.

Evolution and maintenance of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under differing antibiotic selection pressures.

The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal arcA were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, arcA deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal arcA inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and Salmonella Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong parallel mutations in chromosomal arcA were associated with pJXP9 carriage in Salmonella Typhimurium from diverse treatments. Our results thus highlight promoting the loss of the plasmid's MDR region could offer an alternative approach for combating plasmid-encoded antibiotic resistance.

In Situ Expression of Yak IL-22 in Mammary Glands as a Treatment for Bovine Staphylococcus aureus-Induced Mastitis in Mice.

Since the development of dairy farming, bovine mastitis has been a problem plaguing the whole industry, which has led to a decrease in milk production, a reduction in dairy product quality, and an increase in costs. The use of antibiotics to treat mastitis can cause a series of problems, which can bring a series of harm to the animal itself, such as the development of bacterial resistance and dramatic changes in the gut flora. However, the in vivo and in vitro antibacterial activity of yak Interleukin-22 (IL-22) and its application in mastitis caused by Staphylococcus aureus have not been reported. In this study, the mammary gland-specific expression plasmid pLF-IL22 of the yak IL-22 gene was constructed and expressed in MAC-T cells and mammary tissue of postpartum female mice. The coding region of the IL-22 gene in yaks is 573 bp, which can encode 190 amino acids, and the homology difference in the IL-22 gene in yaks is less than 30%, which indicates certain conservation. IL-22 is a hydrophilic protein with a total positive charge of four, the presence of a signal peptide, and the absence of a transmembrane domain. Sufficient expression of IL-22 effectively inhibited the high expression of inflammatory factors caused by Staphylococcus aureus, reduced the symptoms of mammary gland histopathology, and alleviated mastitis. Under the action of IL-22, the intestinal flora of mastitis mice also changed, the abundance of intestinal Bacilli, Prevotellaceae, and Alloprevotella in mice increased after treatment, and the pathogenic bacteria decreased. These findings provide new insights into the potential application of the yak IL-22 gene in the treatment of bovine mastitis in the future.

Metagenomic analysis of sedimentary archives reveals ‘historical’ antibiotic resistance genes diversity increased over recent decades in the environment

Abstract Antibiotic Resistance Genes (ARGs) are widespread in freshwater environments and represent a concealed threat to public health and aquatic eco-system safety. To date, only a limited number of studies have investigated the historical distribution of ARGs and their hosts through the analysis of freshwater sedimentary archives. This research gap constrains our comprehensive of the mechanisms underlying natural bacterial resistance formation during pre-antibiotic era (prior to the 1940s) and the development of human-induced bacterial resistance in post-antibiotic era (since the 1940s). In this study, we examined the vertical distribution patterns of ARGs and their associated hosts within a sedimentary core from a eutrophic lake, employing shotgun sequencing methodology. The findings revealed a marked increase in ARG diversity during post-antibiotic era, and the predominant ARG types identified included those conferring resistance to multidrug, bacitracin, macrolide–lincosamide–streptogramin, beta-lactam, tetracycline, fluoroquinolone, glycopeptide and aminoglycoside, collectively accounting for 78.3%–85.6% of total ARG abundance. A total of 127 ARG subtypes were identified in samples, and 48 ARG subtypes shared across vertical sediment resistome profile with two of them, bacA and bcrA, occurring only in post-antibiotic era. Further, 137 metagenome-assembled genomes (83 species belonging to 12 phyla) were identified as ARG hosts, mainly belonging to the phyla Proteobacteria, Nitrospirota, Chloroflexota, Bacteroidota, Actinobacteriota, Cyanobacteria, and Firmicutes. Significant correlation was found between the diversity of ARG and the concentrations of organic matter and heavy metals, suggesting a common source of contamination. Aside the fact that human-induced eutrophication is a forcing factor acting in parallel to increase ARGs releases in water systems, both being indicators of increased urbanization in the catchment, eutrophication may significantly increase bacterial activity, thereby facilitating the spread of antibiotic-resistant bacteria in environment. This study reveals the marked increased in ARG diversity with the onset of antibiotic use by human societies with potential impact of aquatic ecosystem.

Effect of treatment frequency on the efficacy of superhydrophobic antimicrobial photodynamic therapy of periodontitis in a wistar rat model.

Superhydrophobic antimicrobial photodynamic therapy (SH-aPDT) is advantageous wherein airborne singlet oxygen (1O2) is delivered from a device tip to kill a biofilm with no photosensitizer exposure and no bacterial selectivity (Gram + or Gram -). For effective treatment of periodontitis, the frequency of treatment as well as the optical light fluence required is not known. Thus, we sought to determine whether single or repeated SH-aPDT treatments would work best invivo using two fluence values: 60 and 125 J/cm2. We assessed the efficacy of three protocols: single treatment; interval treatments (days 0, 2, and 7); and consecutive treatments (days 0, 1, and 2). After 30 days of evaluation, we found that, SH-aPDT in 3 consecutive treatments significantly decreased Porphyromonas gingivalis levels compared to single and interval SH-aPDT treatments, as well as SRP-chlorhexidine (CHX) controls (p < 0.05). Notably, clinical parameters also improved (p < 0.05), and histological and stereometric analyses revealed that consecutive SH-aPDT treatments were the most effective for promoting healing and reducing inflammation. Our study shows what works best for SH-aPDT, while also demonstrating SH-aPDT advantages to treatment of periodontitis including no bacterial selectivity (Gram + or Gram -) and preventing the development of bacterial resistance.

Single Atom Engineered Antibiotics Overcome Bacterial Resistance

AbstractThe outbreak of antibiotic‐resistant bacteria, or “superbugs”, poses a global public health hazard due to their resilience against the most effective last‐line antibiotics. Identifying potent antibacterial agents capable of evading bacterial resistance mechanisms represents the ultimate defense strategy. This study shows that –the otherwise essential micronutrient– manganese turns into a broad‐spectrum potent antibiotic when coordinated with a carboxylated nitrogen‐doped graphene. This antibiotic material (termed NGA‐Mn) not only inhibits the growth of a wide spectrum of multidrug‐resistant bacteria but also heals wounds infected by bacteria in vivo and, most importantly, effectively evades bacterial resistance development. NGA‐Mn exhibits up to 25‐fold higher cytocompatibility to human cells than its minimum bacterial inhibitory concentration, demonstrating its potential as a next‐generation antibacterial agent. Experimental findings suggest that NGA‐Mn acts on the outer side of the bacterial cell membrane via a multimolecular collective binding, blocking vital functions in both Gram‐positive and Gram‐negative bacteria. The results underscore the potential of single‐atom engineering toward potent antibiotics, offering simultaneously a long‐sought solution for evading drug resistance development while being cytocompatible to human cells.

Comparative Metabolomics Reveals Changes in the Metabolic Pathways of Ampicillin- and Gentamicin-Resistant Staphylococcus aureus.

Antibiotic resistance is a major global challenge requiring new treatments and a better understanding of the bacterial resistance mechanisms. In this study, we compared ampicillin-resistant (R-AMP) and gentamicin-resistant (R-GEN) Staphylococcus aureus strains with a sensitive strain (ATCC6538) using metabolomics. We identified 109 metabolites; 28 or 31 metabolites in R-AMP or R-GEN differed from those in ATCC6538. Moreover, R-AMP and R-GEN were enriched in five and four pathways, respectively. R-AMP showed significantly up-regulated amino acid metabolism and down-regulated energy metabolism, whereas R-GEN exhibited an overall decrease in metabolism, including carbohydrate, energy, and amino acid metabolism. Furthermore, the activities of the metabolism-related enzymes pyruvate dehydrogenase and TCA cycle dehydrogenases were inhibited in antibiotic-resistant bacteria. Significant decreases in NADH and ATP levels were also observed. In addition, the arginine biosynthesis pathway, which is related to nitric oxide (NO) production, was enriched in both antibiotic-resistant strains. Enhanced NO synthase activity in S. aureus promoted NO production, which further reduced reactive oxygen species, mediating the development of bacterial resistance to ampicillin and gentamicin. This study reveals that bacterial resistance affects metabolic profile, and changes in energy metabolism and arginine biosynthesis are important factors leading to drug resistance in S. aureus.

Superhydrophobic Dressing for Singlet Oxygen Delivery in Antimicrobial Photodynamic Therapy against Multidrug-Resistant Bacterial Biofilms.

The rise of antimicrobial resistance poses a critical public health threat worldwide. While antimicrobial photodynamic therapy (aPDT) has demonstrated efficacy against multidrug-resistant (MDR) bacteria, its effectiveness can be limited by several factors, including the delivery of the photosensitizer (PS) to the site of interest and the development of bacterial resistance to PS uptake. There is a need for alternative methods, one of which is superhydrophobic antimicrobial photodynamic therapy (SH-aPDT), which we report here. SH-aPDT is a technique that isolates the PS on a superhydrophobic (SH) membrane, generating airborne singlet oxygen (1O2) that can diffuse up to 1 mm away from the membrane. In this study, we developed a SH polydimethylsiloxane dressing coated with PS verteporfin. These dressings contain air channels called a plastron for supplying oxygen for aPDT and are designed so that there is no direct contact of the PS with the tissue. Our investigation focuses on the efficacy of SH-aPDT on biofilms formed by drug-sensitive and MDR strains of Gram-positive (Staphylococcus aureus and S. aureus methicillin-resistant) and Gram-negative bacteria (Pseudomonas aeruginosa and P. aeruginosa carbapenem-resistant). SH-aPDT reduces bacterial biofilms by approximately 3 log with a concomitant decrease in their metabolism as measured by MTT. Additionally, the treatment disrupted extracellular polymeric substances, leading to a decrease in biomass and biofilm thickness. This innovative SH-aPDT approach holds great potential for combating antimicrobial resistance, offering an effective strategy to address the challenges posed by drug-resistant wound infections.

Módulo de promoción del uso responsable de antimicrobianos en odontología: diseño instruccional guiado por la teoría de carga cognitiva

IntroductionAproximately 30% to 50% of annual antimicrobial prescriptions are inappropriate or unnecessary, enhancing the development of bacterial resistance. It has been proposed that the responsible use of antimicrobials in undergraduate programs be emphasized. However, teachers usually do not manage effective strategies for this purpose. Aims1. Develop an instructional design, guided by the cognitive load theory, of a teaching and learning module to promote responsible use of antimicrobials 2. Evaluate the educational impact of the module on third-year Dental students. MethodsAction research and mixed methodology in four phases. i. Identification of learning needs and outcomes; ii. Instructional design guided by cognitive load theory; iii. Module implementation; iv. Educational impact on students was evaluated using satisfaction surveys, self-reports of learning outcomes achievement and a pre-post knowledge test. Descriptive and analytical statistical analysis (Wilcoxon test) and qualitative content analysis were used. ResultsThe antimicrobial module was designed in Canvas (LMS), allocating protected time for study and a classroom session. The educational impact was evaluated in 48 students. The satisfaction survey reported positive results on their 10 items (minimum 81.3%). The results of the self-reports of achievement of 7 learning outcomes and the pre-post test of 18 questions were statistically significant (p<0.001). ConclusionsThe design of this module could serve as a guide to promote the responsible use of antimicrobials while achieving greater satisfaction with students’ experience and learning outcomes.

Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides

Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

Construction of a one-stop N-doped negatively charged carbon dot nanoplatform with antibacterial and anti-inflammatory dual activities for wound infection based on biocompatibility

The development of bacterial resistance significantly contributes to the persistence of infections. Although previous studies have highlighted the benefits of metal-doped positive carbon nanodots in managing bacterial wound infections, their mechanism of action is relatively simple and they may pose potential hazards to human cells. Therefore, it is essential to develop a one-stop carbon dot nanoplatform that offers high biocompatibility, antibacterial properties, and anti-inflammatory activities for wound infection management. This study explores the antibacterial efficacy, without detectable resistance, and wound-healing potential of nitrogen-doped (N-doped) negatively charged carbon dots (TPP-CDs). These carbon dots are synthesized using tannic acid (TA), polyethylene polyamine, and polyethylene glycol (PEG) as precursors, with a focus on their biocompatibility. Numerous systematic studies have shown that TPP-CDs can effectively destroy bacterial biofilms and deoxyribonucleic acid (DNA), while also inducing oxidative stress, leading to a potent antimicrobial effect. TPP-CDs also demonstrate the ability to scavenge excess free radicals, promote cellular proliferation, and inhibit inflammatory factors, all of which contribute to improved wound healing. TPP-CDs also demonstrate favorable cell imaging capabilities. These findings suggest that N-doped negatively charged TPP-CDs hold significant potential for treating bacterial infections and offer practical insights for their application in the medical field.

A Comprehensive Analysis of Liposomal-Based Nanocarriers for Treating Skin and Soft Tissue Infection.

Bacterial skin and soft tissue infections (SSTIs) are widespread microbic invasions of the skin and deeper tissues. Topical drug delivery systems are the most favored administration pathway when treating SSTIs. This is down to their minimal risk of inducing systemic adverse events, reduced development of bacterial resistance, and ease of application. However, they have several drawbacks, including the lack of control over the drug release profile, skin irritations, and the limited permeability of certain compounds through the skin. To address these limitations, several nanocarrier systems were developed, with nanoliposomes standing out as the leading delivery system for the topical management of SSTIs. Despite considerable research into liposomes over the past decade, there remains a gap in detailed knowledge about designing these carriers specifically for SSTIs. Consequently, there is a pressing need for comprehensive research that focuses on the use of nanoliposomes for SSTIs and offers an extensive understanding of both SSTIs and liposomal formulations. This review explores bacterial SSTIs, covering their epidemiology, classification, microbiology, and management. It emphasizes the contribution of liposome-based nanovesicles in enhancing the local administration of antibiotics and natural antibacterial compounds for SSTI management. It also delves into the effects of liposomal formulation changes on the disease therapeutic outcomes. Additionally, it provides a guide for aligning the characteristics of the liposomes with the infection types, depths, properties, and causative agents. This signifies a substantial leap forward in the domains of drug design, development, and delivery.

Guided Plasma Application in Dentistry-An Alternative to Antibiotic Therapy.

Cold atmospheric plasma (CAP) is a promising alternative to antibiotics and chemical substances in dentistry that can reduce the risk of unwanted side effects and bacterial resistance. AmbiJet is a device that can ignite and deliver plasma directly to the site of action for maximum effectiveness. The aim of the study was to investigate its antimicrobial efficacy and the possible development of bacterial resistance. The antimicrobial effect of the plasma was tested under aerobic and anaerobic conditions on bacteria (five aerobic, three anaerobic (Gram +/-)) that are relevant in dentistry. The application times varied from 1 to 7 min. Possible bacterial resistance was evaluated by repeated plasma applications (10 times in 50 days). A possible increase in temperature was measured. Plasma effectively killed 106 seeded aerobic and anaerobic bacteria after an application time of 1 min per 10 mm2. Neither the development of resistance nor an increase in temperature above 40 °C was observed, so patient discomfort can be ruled out. The plasma treatment proved to be effective under anaerobic conditions, so the influence of ROS can be questioned. Our results show that AmbiJet efficiently eliminates pathogenic oral bacteria. Therefore, it can be advocated for clinical therapeutic use.

Deciphering the Intracellular Action of the Antimicrobial Peptide A11 via an In-Depth Analysis of Its Effect on the Global Proteome of Acinetobacter baumannii.

The potential antimicrobial activity and low propensity to induce the development of bacterial resistance have rendered antimicrobial peptides (AMPs) as novel and ideal candidate therapeutic agents for the treatment of infections caused by drug-resistant pathogenic bacteria. The targeting of bacterial membranes by AMPs has been typically considered their sole mode of action; however, increasing evidence supports the existence of multiple and complementary functions of AMPs that result in bacterial death. An in-depth characterization of their mechanism of action could facilitate further research and development of AMPs with higher potency. The current study employs biophysics and proteomics approaches to unveil the mechanisms underlying the antibacterial activity of A11, a potential candidate AMP, against Acinetobacter baumannii, a leading cause of hospital-acquired infections (HAIs) and consequently, a serious global threat. A11 peptide was found to induce membrane depolarization to a high extent, as revealed by flow cytometry and electron microscopy analyses. The prompt intracellular penetration of A11 peptide, observed using confocal microscopy, was found to occur concomitantly with a very low degree of membrane lysis, suggesting that its mode of action predominantly involves a nonlytic killing mechanism. Quantitative proteomics analysis employed for obtaining insights into the mechanisms underlying the antimicrobial activity of A11 peptide revealed that it disrupted energy metabolism, interfered with protein homeostasis, and inhibited fatty acid synthesis that is essential for cell membrane integrity; all these impacted the cellular functions of A. baumannii. A11 treatment also impacted signal transduction associated with the regulation of biofilm formation, hindered the stress response, and influenced DNA repair processes; these are all crucial survival mechanisms of A. baumannii. Additionally, robust antibacterial activity was exhibited by A11 peptide against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates of A. baumannii; moreover, A11 peptide exhibited synergy with levofloxacin and minocycline as well as low propensity for inducing resistance. Taken together, the findings emphasize the therapeutic potential of A11 peptide as an antibacterial agent against drug-resistant A. baumannii and underscore the need for further investigation.