Phytochemical and ethnomedicinal evidences of the use of Alternanthera brasiliana (L.) Kuntze against infectious diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Popularly known as "penicilina" and "terramicina", Alternanthera brasiliana (L.) Kuntze belongs to the Amaranthaceae family and stands out for its ethnomedicinal uses in the treatment of infections caused by pathogenic microorganisms in some countries. AIM OF THE STUDY: The present study aimed to carry out a literature review and analyze whether the scientific evidence really validates the numerous indications for the use of A. brasiliana in traditional medicine for the treatment of infectious diseases. Phytochemical and toxicological studies related to this species were also analyzed. MATERIAL AND METHODS: Scientific documents were retrieved from Google Scholar, PubMed®, ScienceDirect®, SciELO, SpringerLink®, Scopus®, and Web of Science™ databases. The literature was reviewed from the first report on the antimicrobial activity of A. brasiliana in 1994 until April 2024. RESULTS: According to the scientific documents analyzed, it was observed that A. brasiliana is widely used as a natural antibiotic for the treatment of infectious diseases in Brazil, mainly in the states of Rio Grande do Sul, Mato Grosso, and Minas Gerais. Its ethnomedicinal uses have also been reported in other countries such as Colombia and India. The leaves (78%) of A. brasiliana are the main parts used in the preparation of herbal medicines by traditional communities. Several A. brasiliana extracts showed low activity when evaluated against pathogens, including gram-positive bacteria, gram-negative bacteria, parasitic protozoa, and fungi. Only two studies reported that extracts from this plant showed high activity against the herpes simplex virus, Mycobacterium smegmatis, and Candida albicans. Phytochemicals belonging to the classes of phenolic compounds and flavonoid (52%), saturated and unsaturated fatty acids (33%), steroids and phytosterols (8%), terpenoids (5%), and fatty alcohol esters (2%) were identified in A. brasiliana. Toxicity (in vivo) and cytotoxicity (in vitro) studies of polar and non-polar extracts obtained from A. brasiliana leaves indicated that this plant is biologically safe. CONCLUSION: Despite being widely used as a natural antibiotic by traditional communities, scientific investigations related to the antimicrobial potential of A. brasiliana extracts have indicated inactivity against several pathogens.

Bactericidal Efficacy of the Combination of Maresin-like Proresolving Mediators and Carbenicillin Action on Biofilm-Forming Burn Trauma Infection-Related Bacteria.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma-related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotic, carbenicillin (carb), on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of Gram-positive and Gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

Role of CARD9 in Cell- and Organ-Specific Immune Responses in Various Infections.

The caspase recruitment domain-containing protein 9 (CARD9) is an intracellular adaptor protein that is abundantly expressed in cells of the myeloid lineage, such as neutrophils, macrophages, and dendritic cells. CARD9 plays a critical role in host immunity against infections caused by fungi, bacteria, and viruses. A CARD9 deficiency impairs the production of inflammatory cytokines and chemokines as well as migration and infiltration, thereby increasing susceptibility to infections. However, CARD9 signaling varies depending on the pathogen causing the infection. Furthermore, different studies have reported altered CARD9-mediated signaling even with the same pathogen. Therefore, this review focuses on and elucidates the current literature on varied CARD9 signaling in response to various infectious stimuli in humans and experimental mice models.

Role of Metal-Organic Frameworks (MOFs) in treating and diagnosing microbial infections.

This review article highlights the innovative role of metal-organic frameworks (MOFs) in addressing global healthcare challenges related to microbial infections. MOFs, comprised of metal nodes and organic ligands, offer unique properties that can be applied in the treatment and diagnosis of these infections. Traditional methods, such as antibiotics and conventional diagnostics, face issues such as antibiotic resistance and diagnostic limitations. MOFs, with their highly porous and customizable structure, can encapsulate and deliver therapeutic or diagnostic molecules precisely. Their large surface area and customizable pore structures allow for sensitive detection and selective recognition of microbial pathogens. They also show potential in delivering therapeutic agents to infection sites, enabling controlled release and possible synergistic effects. However, challenges like optimizing synthesis techniques, enhancing stability, and developing targeted delivery systems remain. Regulatory and safety considerations for clinical translation also need to be addressed. This review not only explores the potential of MOFs in treating and diagnosing microbial infections but also emphasizes their unique approach and discusses existing challenges and future directions.

Exosomes: Friends or Foes in Microbial Infections?

The use of new approaches is necessary to address the global issue of infections caused by drug-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) is a promising approach that reduces the emergence of drug resistance, and no resistance has been reported thus far. APDT involves using a photosensitizer (PS), a light source, and oxygen. The mechanism of aPDT is that a specific wavelength of light is directed at the PS in the presence of oxygen, which activates the PS and generates reactive oxygen species (ROS), consequently causing damage to microbial cells. However, due to the PS's poor stability, low solubility in water, and limited bioavailability, it is necessary to employ drug delivery platforms to enhance the effectiveness of PS in photodynamic therapy (PDT). Exosomes are considered a desirable carrier for PS due to their specific characteristics, such as low immunogenicity, innate stability, and high ability to penetrate cells, making them a promising platform for drug delivery. Additionally, exosomes also possess antimicrobial properties, although in some cases, they may enhance microbial pathogenicity. As there are limited studies on the use of exosomes for drug delivery in microbial infections, this review aims to present significant points that can provide accurate insights.

Machine Learning-Assisted Optimization of Drug Combinations in Zeolite-Based Delivery Systems for Melanoma Therapy.

Two independent artificial neural network (ANN) models were used to determine the optimal drug combination of zeolite-based delivery systems (ZDS) for cancer therapy. The systems were based on the NaY zeolite using silver (Ag+) and 5-fluorouracil (5-FU) as antimicrobial and antineoplastic agents. Different ZDS samples were prepared, and their characterization indicates the successful incorporation of both pharmacologically active species without any relevant changes to the zeolite structure. Silver acts as a counterion of the negative framework, and 5-FU retains its molecular integrity. The data from the A375 cell viability assays, involving ZDS samples (solid phase), 5-FU, and Ag+ aqueous solutions (liquid phase), were used to train two independent machine learning (ML) models. Both models exhibited a high level of accuracy in predicting the experimental cell viability results, allowing the development of a novel protocol for virtual cell viability assays. The findings suggest that the incorporation of both Ag and 5-FU into the zeolite structure significantly potentiates their anticancer activity when compared to that of the liquid phase. Additionally, two optimal AgY/5-FU@Y ratios were proposed to achieve the best cell viability outcomes. The ZDS also exhibited significant efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus); the predicted combination ratio is also effective against S. aureus, underscoring the potential of this approach as a therapeutic option for cancer-associated bacterial infections.

Radiological and Imaging Evidence in the Diagnosis and Management of Microbial Infections: An Update.

Microbial infections are extremely prevalent throughout the world. Bacteria, fungi, parasites, and viruses generally cause them. Most microbial infections spread from humans to humans and from animals to humans. A vast majority of microbial infections are self-limiting. However, some microbial infections result in severe morbidity and mortality. The diagnosis of microbial infections generally depends on the direct demonstration of microbes in human clinical specimens through microscopy followed by culture. Some microbes are uncultivable, and among those that are cultivable, some take a very long time to grow in the laboratory. This causes delays in the diagnosis that may result in poor patient outcomes. Serological and molecular methods like enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), respectively, have been extensively used to diagnose infectious diseases. However, these require costly infrastructure and adequate personnel training. In this context, alternative, more efficient, and rapid detection methods for the diagnosis of microbial infections are warranted. In this review, we comprehensively discuss the role played by radiological investigations in the diagnosis and management of infectious diseases.

Systemic assessment of solute carrier family 11-member A1 (rs17235409) gene polymorphism and Mycobacterium Tuberculosis Risk in Asian and caucasian population: A comprehensive updated meta-analysis.

Background: The present meta-analysis was assessed to confirm the association between solute carrier family 11-member A1 (SLC11A1) gene (rs17235409) polymorphism with the Mycobacterium tuberculosis infection in the Asian and Caucasian populations. Methods: A search was conducted using the databases including Google Scholar, Science Direct, Embase, and PubMed to find the case-control studies related to SLC11A1 gene polymorphism and tuberculosis (TB) infection. The MetaGenyo programme was used to perform statistical analyses of the data. The odds ratio and 95% confidence interval were calculated based on genetic models such as allelic model, dominant model, recessive model, and overdominant. The heterogeneity and publication bias for the present study were examined to assess its quality. The study was registered in PROSPERO (ID Number: 461434). Results: This current study revealed the association between the SLC11A1 gene polymorphism with TB. The statistical value obtained at P < 0.05 was deemed to be statistically significant. The meta-analysis results revealed that allele contrast and recessive models are significant association between SLC11A1 gene polymorphism with risk of TB infections, and dominant and overdominant models have no significant association with TB risk. In addition, the subgroup analysis based on the ethnicity dominant revealed a significant association with the risk of TB. Therefore, this results that the gene SLC11A1 has a significant association for allelic and recessive and has no significant association for dominant and overdominant with the risk of TB. Conclusion: According to the data retrieved from the database with respect to the present study revealed that SLC11A1 gene polymorphism rs17235409 for allelic, recessive models have been associated with TB infections, but dominant and overdominant models have not been associated with TB infections.

Pyroptosis in microbial infectious diseases.

Pyroptosis is a gasdermins-mediated programmed cell death that plays an essential role in immune regulation, and its role in autoimmune disease and cancer has been studied extensively. Increasing evidence shows that various microbial infections can lead to pyroptosis, associated with the occurrence and development of microbial infectious diseases. This study reviews the recent advances in pyroptosis in microbial infection, including bacterial, viral, and fungal infections. We also explore potential therapeutic strategies for treating microbial infection-related diseases by targeting pyroptosis.

Current risks of microbial infections in fish and their prevention methods: A review.

A fast-expanding sector of agriculture worldwide is aquaculture. The production of fish internationally accounts for around 44 % of the total. Even though the aquaculture environment presents several difficulties, the current development in aquaculture production comes with an increase in infectious diseases, which significantly impacts the production, profitability, and sustainability of the worldwide aquaculture business. Many infectious agents, such as bacteria, viruses, fungi and parasites are causative agents for fish infections. Most infectious diseases found in all types of fish like marine water, freshwater and ornamental fishes are caused by bacteria, with many of them serving as secondary opportunistic invaders that attack sick animals by affecting their natural host immunity. To overcome this, addressing health issues based on methods that have been scientifically verified and advised will help lessen the effects of fish disease. This review aims to highlight some of the common microbial-infecting agents of fish in all types of aquatic systems and their effective methods for preventing infections in aquaculture.

Microbial infections as potential risk factors for lung cancer: Investigating the role of human papillomavirus and chlamydia pneumoniae.

Background: Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods: Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model. Results: The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (OR = 2.33, 95% CI = 1.57-3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33-17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27-11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02-1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57-1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61-1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30-2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10-2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42-1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42-105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions: Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer.

Emergence of microbial infections in some hospitals of Cairo, Egypt: studying their corresponding antimicrobial resistance profiles.

BACKGROUND: Antimicrobial resistance is one of the ten major public health threats facing humanity, especially in developing countries. Identification of the pathogens responsible for different microbial infections and antimicrobial resistance patterns are important to help clinicians to choose the correct empirical drugs and provide optimal patient care. METHODS: During the period from November 2020 to January 2021, one hundred microbial isolates were collected randomly from different specimens from some hospitals in Cairo, Egypt. Sputum and chest specimens were from COVID-19 patients. Antimicrobial susceptibility testing was performed according to CLSI guidelines. RESULTS: Most microbial infections were more common in males and in elderly people over 45 years of age. They were caused by Gram-negative, Gram-positive bacteria, and yeast isolates that represented 69%, 15%, and 16%, respectively. Uropathogenic Escherichia coli (35%) were the most prevalent microbial isolates and showed high resistance rates towards penicillin, ampicillin, and cefixime, followed by Klebsiella spp. (13%) and Candida spp. (16%). Of all microbial isolates, Acinetobacter spp., Serratia spp., Hafnia alvei, and Klebsiella ozaenae were extremely multidrug-resistant (MDR) and have resisted all antibiotic classes used, except for glycylcycline, in varying degrees. Acinetobacter spp., Serratia spp., and Candida spp. were secondary microbial infections in COVID-19 patients, while H. alvei was a bloodstream infection isolate and K. ozaenae was recorded in most infections. Moreover, about half of Staphylococcus aureus strains were MRSA isolates and reported low rates of resistance to glycylcycline and linezolid. In comparison, Candida spp. showed high resistance rates between 77 and 100% to azole drugs and terbinafine, while no resistance rate towards nystatin was reported. Indeed, glycylcycline, linezolid, and nystatin were considered the drugs of choice for the treatment of MDR infections. CONCLUSION: The prevalence of antimicrobial resistance in some Egyptian hospitals was high among Gram-negative, Gram-positive bacteria, and candida spp. The high resistance pattern -especially in secondary microbial infections in COVID-19 patients- to most antibiotics used is a matter of great concern, portends an inevitable catastrophe, and requires continuous monitoring to avoid the evolution of new generations.

Egg Yolk Antibody for Passive Immunization: Status, Challenges, and Prospects.

The immunoglobulin Y (IgY) derived from hyperimmune egg yolk is a promising passive immune agent to combat microbial infections in humans and livestock. Numerous studies have been performed to develop specific egg yolk IgY for pathogen control, but with limited success. To date, the efficacy of commercial IgY products, which are all delivered through an oral route, has not been approved or endorsed by any regulatory authorities. Several challenging issues of the IgY-based passive immunization, which were not fully recognized and holistically discussed in previous publications, have impeded the development of effective egg yolk IgY products for humans and animals. This review summarizes major challenges of this technology, including in vivo stability, purification, heterologous immunogenicity, and repertoire diversity of egg yolk IgY. To tackle these challenges, potential solutions, such as encapsulation technologies to stabilize IgY, are discussed. Exploration of this technology to combat the COVID-19 pandemic is also updated in this review.

Antiviral Peptide-Based Conjugates: State of the Art and Future Perspectives.

Infectious diseases caused by microbial pathogens (bacteria, virus, fungi, parasites) claim millions of deaths per year worldwide and have become a serious challenge to global human health in our century. Viral infections are particularly notable in this regard, not only because humankind is facing some of the deadliest viral pandemics in recent history, but also because the arsenal of drugs to combat the high levels of mutation, and hence the antigenic variability of (mostly RNA) viruses, is disturbingly scarce. Therefore, the search for new antivirals able to successfully fight infection with minimal or no adverse effects on the host is a pressing task. Traditionally, antiviral therapies have relied on relatively small-sized drugs acting as proteases, polymerases, integrase inhibitors, etc. In recent decades, novel approaches involving targeted delivery such as that achieved by peptide-drug conjugates (PDCs) have gained attention as alternative (pro)drugs for tackling viral diseases. Antiviral PDC therapeutics typically involve one or more small drug molecules conjugated to a cell-penetrating peptide (CPP) carrier either directly or through a linker. Such integration of two bioactive elements into a single molecular entity is primarily aimed at achieving improved bioavailability in conditions where conventional drugs are challenged, but may also turn up novel unexpected functionalities and applications. Advances in peptide medicinal chemistry have eased the way to antiviral PDCs, but challenges remain on the way to therapeutic success. In this paper, we review current antiviral CPP-drug conjugates (antiviral PDCs), with emphasis on the types of CPP and antiviral cargo. We integrate the conjugate and the chemical approaches most often applied to combine both entities. Additionally, we comment on various obstacles faced in the design of antiviral PDCs and on the future outlooks for this class of antiviral therapeutics.

Intracellular complement: Evidence, definitions, controversies, and solutions.

The term "intracellular complement" has been introduced recently as an umbrella term to distinguish functions of complement proteins that take place intracellularly, rather than in the extracellular environment. However, this rather undefined term leaves some confusion as to the classification of what intracellular complement really is, and as to which intracellular compartment(s) it should refer to. In this review, we will describe the evidence for both canonical and non-canonical functions of intracellular complement proteins, as well as the current controversies and unanswered questions as to the nature of the intracellular complement. We also suggest new terms to facilitate the accurate description and discussion of specific forms of intracellular complement and call for future experiments that will be required to provide more definitive evidence and a better understanding of the mechanisms of intracellular complement activity.

Herpesvirus Infections in the Human Brain: A Neural Cell Model of the Complement System Derived from Induced Pluripotent Stem Cells.

BACKGROUND: Herpesviruses alter cognitive functions in humans following acute infections; progressive cognitive decline and dementia have also been suggested. It is important to understand the pathogenic mechanisms of such infections. The complement system - comprising functionally related proteins integral for systemic innate and adaptive immunity - is an important component of host responses. The complement system has specialized functions in the brain. Still, the dynamics of the brain complement system are still poorly understood. Many complement proteins have limited access to the brain from plasma, necessitating synthesis and specific regulation of expression in the brain; thus, complement protein synthesis, activation, regulation, and signaling should be investigated in human brain-relevant cellular models. Cells derived from human-induced pluripotent stem cells (hiPSCs) could enable tractable models. METHODS: Human-induced pluripotent stem cells were differentiated into neuronal (hi-N) and microglial (hi-M) cells that were cultured with primary culture human astrocyte-like cells (ha-D). Gene expression analyses and complement protein levels were analyzed in mono- and co-cultures. RESULTS: Transcript levels of complement proteins differ by cell type and co-culture conditions, with evidence for cellular crosstalk in co-cultures. Hi-N and hi-M cells have distinct patterns of expression of complement receptors, soluble factors, and regulatory proteins. hi-N cells produce complement factor 4 (C4) and factor B (FB), whereas hi-M cells produce complement factor 2 (C2) and complement factor 3 (C3). Thus, neither hi-N nor hi-M cells can form either of the C3-convertases - C4bC2a and C3bBb. However, when hi-N and hi-M cells are combined in co-cultures, both types of functional C3 convertase are produced, indicated by elevated levels of the cleaved C3 protein, C3a. CONCLUSIONS: hiPSC-derived co-culture models can be used to study viral infection in the brain, particularly complement receptor and function in relation to cellular "crosstalk." The models could be refined to further investigate pathogenic mechanisms.

Bioassay-guided isolation and characterization of lead antimicrobial compounds from Acacia hydaspica plant extract.

Acacia hydaspica possesses varied pharmacological attributes. We aimed to examine the antimicrobial potential and isolate the active antimicrobial metabolites. The plant extract was fractionated and the antimicrobial activity of the crude extract, fractions and compounds was tested by agar well diffusion and agar tube dilution and broth dilution methods. Bacterial strains selected for bioactivity testing were Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii while selected strains from kingdom fungi were Candida albicans, Cryptococcus neoformans, Fusarium solani and Aspergillus. The active compounds were isolated from Acacia hydaspica by bioassay-guided fractionation and identified by nuclear magnetic resonance and spectroscopic techniques. S. aureus cell surface proteins, Autolysins (Atl), Clumping factor A (ClfA), and Fibronectin Binding Proteins (FnBP), were molecularly docked with Catechin 3-O-gallate (CG) and Methyl gallate (MG) and binding energy and molecular interactions between the proteins and compounds were analyzed. Ethyl acetate (AHE) and Butanol (AHB) fractions of A. hydaspica were the most active fractions against tested microbial strains. Therefore, both were subjected to bioassay-directed fractionation which led to the isolation of one pure active antimicrobial AHE and one active pure compound from AHB fraction besides active enriched isolates. Methyl-gallate (MG) and catechin-3-gallate (CG) are active compounds extracted from AHE and AHB fractions respectively. In antibacterial testing MG significantly inhibited the growth of E. coli (MIC50 = 21.5 µg/ml), B. subtilus (MIC50 = 23 µg/ml) and S. aureus (MIC50 = 39.1 µg/ml) while moderate to low activity was noticed against other tested bacterial strains. Antifungal testing reveals that MG showed potent antifungal activity against F. solani (MIC50 = 33.9 µg/ml) and A. niger (MIC50 = 41.5 µg/ml) while lower antifungal activity was seen in other tested strains. AHB fractions and pure compound (CG) showed specific antibacterial activity against S. aureus only (MIC50 = 10.1 µg/ml) while compound and enriched fractions showed moderate to no activity against other bacterial and fungal strains respectively. Molecular docking analysis revealed that CG interacted more strongly with the cell surface proteins than MG. Among these proteins, CG made a stronger complex with ClfA (binding affinity - 9.7) with nine hydrophobic interactions and five hydrogen bonds. Methyl gallate (MG) and catechin 3-O-gallate (CG) are the major antimicrobial compound from A. hydaspica that inhibit the growth of specific microbes. The occurrence of MG and CG endorse the traditional antimicrobial applicability of A. hydaspica, and it can be a legitimate alternative to control specific microbial infections.

Polyglycerol Adipate-Grafted Polycaprolactone Nanoparticles as Carriers for the Antimicrobial Compound Usnic Acid.

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved.