Host defence peptides (HDPs) are critical components of innate immunity. Despite their diversity, they share common features including a structural signature, designated "γ-core motif". We reasoned that for each HDPs evolved from an ancestral γ-core, the latter should be the evolutionary starting point of the molecule, i.e. it should represent a structural scaffold for the modular construction of the full-length molecule, and possess biological properties. We explored the γ-core of human β-defensin 3 (HBD3) and found that it: (a) is the folding nucleus of HBD3; (b) folds rapidly and is stable in human serum; (c) displays antibacterial activity; (d) binds to CD98, which mediates HBD3 internalization in eukaryotic cells; (e) exerts antiviral activity against human immunodeficiency virus and herpes simplex virus; and (f) is not toxic to human cells. These results demonstrate that the γ-core within HBD3 is the ancestral core of the full-length molecule and is a viable HDP per se, since it is endowed with the most important biological features of HBD3. Notably, the small, stable scaffold of the HBD3 γ-core can be exploited to design disease-specific antimicrobial agents.Host defence peptides (HDPs) are a critical component of innate immunity, and represent a first line of defence against infection by a broad spectrum of pathogens. HDP expression is found in the host tissues most exposed to microorganisms (skin and internal epithelia of e.g. the respiratory and gastrointestinal tracts) and in the cells of the immune system (macrophages, lymphocytes, platelets etc.)1 . Since a number of pathogens that are refractory to conventional antibiotics are sensitive to HDPs, there is considerable interest in the development of these peptides as therapeutics 2 . Moreover, it is becoming increasingly clear that these multifunctional peptides exert other functions besides antimicrobial action, for example, they are involved in the immune surveillance against cancer 3 . Accordingly, almost 1,000 different HDPs have been identified 4 . Despite this diversity, all HDPs share the following features: a small size (< 10 kDa), a positive charge at neutral pH, and an amphipathic structure. This secondary structure drives the interaction of HDP with lipid bilayers and, critically, it enables selectivity between

The ocular surface microbiota refers to the resident non-pathogenic microorganisms that colonize conjunctiva and cornea. Several studies have shown that ocular surface epithelial cells can respond selectively to specific components of ocular pathogenic bacteria by producing pro-inflammatory cytokines and, in contrast, they do not respond to non-pathogenic bacteria, thus supporting the colonization by a real microbiota. However, the analysis of the ocular microbiome composition is essential for understanding the pathophysiology of various ophthalmic diseases. In this scenario, the first studies, which used microbiological culture techniques, reported a less diverse profile of the ocular microbiota compared with that recently discovered using new molecular-based methods. Indeed, until a few years ago, the microbiota of the ocular surface appeared to be dominated by Gram-positive and a few Gram-negative bacteria, as well as some fungal strains. In contrast, genomics has nowadays detected a remarkable diversity in the ocular surface microorganisms. Furthermore, recent studies suggest that the microbiota of other areas of the body, such as the gut and oral microbiota, are involved in the pathophysiology of several ophthalmic diseases. The aim of the present study is to highlight the current evidence on the ocular surface microbiota to better understand it and to investigate its potential role in the development of ophthalmic diseases.

In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably the field where these molecules find extraordinary applicability, and this is probably due to their multi-valency and to the fact that several other chemicals can be coupled to them to obtain desired compounds. In this review we will describe the different production strategies and the tools and technologies for the study of their characteristics. Finally, we provide a panoramic overview of their applications to meet biomedical needs, especially their use as novel antimicrobials.

Bloodstream infections (BSIs) are among the leading causes of morbidity and mortality worldwide, among infectious diseases. Local knowledge of the main bacteria involved in BSIs and their associated antibiotic susceptibility patterns is essential to rationalize the empiric antimicrobial therapy. The aim of this study was to define the incidence of infection and evaluate the antimicrobial resistance profile of the main pathogens involved in BSIs. This study enrolled patients of all ages and both sexes admitted to the University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy between January 2015 to December 2019. Bacterial identification and antibiotic susceptibility testing were performed with Vitek 2. A number of 3.949 positive blood cultures were included out of 24,694 total blood cultures from 2015 to 2019. Coagulase-negative staphylococci (CoNS) were identified as the main bacteria that caused BSI (17.4%), followed by Staphylococcus aureus (12.3%), Escherichia coli (10.9%), and Klebsiella pneumoniae (9.4%). Gram-positive bacteria were highly resistant to Penicillin G and Oxacillin, while Gram-negative strains to Ciprofloxacin, Cefotaxime, Ceftazidime, and Amoxicillin-clavulanate. High susceptibility to Vancomycin, Linezolid, and Daptomycin was observed among Gram-positive strains. Fosfomycin showed the best performance to treatment Gram-negative BSIs. Our study found an increase in resistance to the latest generation of antibiotics over the years. This suggests an urgent need to improve antimicrobial management programs to optimize empirical therapy in BSI.

The increasing spread of multidrug-resistant pathogenic bacteria is one of the major threats to public health worldwide. Bacteria can acquire antibiotic resistance and virulence genes through horizontal gene transfer (HGT). A novel horizontal gene transfer mechanism mediated by outer membrane vesicles (OMVs) has been recently identified. OMVs are rounded nanostructures released during their growth by Gram-negative bacteria. Biologically active toxins and virulence factors are often entrapped within these vesicles that behave as molecular carriers. Recently, OMVs have been reported to contain DNA molecules, but little is known about the vesicle packaging, release, and transfer mechanisms. The present review highlights the role of OMVs in HGT processes in Gram-negative bacteria.

Pre-treatment MoS 2 NSs Co-treatment MoS 2 NSs Cell Pre-treatment MoS 2 NSs Post treatment MoS 2 NSs Pre-treatment GO NSs Co-treatment GO NSs Cell Pre-treatment GO NSs Post treatment GO NSs The interaction of 2DM with the virus is associated with color code starting from hot red being the strongest interaction to lighter until white being the weakest interaction.

Urinary tract infections (UTIs) are the most common and expensive health problem globally. The treatment of UTIs is difficult owing to the onset of antibiotic-resistant bacterial strains. The aim of this study was to define the incidence of infections, identify the bacteria responsible, and identify the antimicrobial resistance profile. Patients of all ages and both sexes were included in the study, all admitted to University Hospital of Campania “Luigi Vanvitelli”, between January 2017 and December 2018. Bacterial identification and antibiotic susceptibility testing were performed using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and Phoenix BD. Among the 1745 studied patients, 541 (31%) and 1204 (69%) were positive and negative for bacterial growth, respectively. Of 541 positive patients, 325 (60%) were females, while 216 (39.9%) were males. The largest number of positive subjects was recorded in the elderly (>61 years). Among the pathogenic strains, 425 (78.5%) were Gram-negative, 107 (19.7%) were Gram-positive, and 9 (1.7%) were Candida species. The most isolated Gram-negative strain is Escherichia coli (E. coli) (53.5%). The most frequent Gram-positive strain was Enterococcus faecalis (E. faecalis) (12.9%). Gram-negative bacteria were highly resistant to ampicillin, whereas Gram-positive bacteria were highly resistant to erythromycin.

The COVID-19 pandemic has evidenced the urgent need for the discovery of broad-spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication cycle. Therefore, antimicrobial peptides (AMPs) have been identified as promising antiviral agents that could help to overcome this limitation and provide compounds able to act on more than a single viral family. We evaluated the antiviral activity of an amphibian peptide known for its strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, namely Temporin L (TL). Previous studies have revealed that TL is endowed with widespread antimicrobial activity and possesses marked haemolytic activity. Therefore, we analyzed TL and a previously identified TL derivative (Pro3, DLeu9 TL, where glutamine at position 3 is replaced with proline, and the D-Leucine enantiomer is present at position 9) as well as its analogs, for their activity against a wide panel of viruses comprising enveloped, naked, DNA and RNA viruses. We report significant inhibition activity against herpesviruses, paramyxoviruses, influenza virus and coronaviruses, including SARS-CoV-2. Moreover, we further modified our best candidate by lipidation and demonstrated a highly reduced cytotoxicity with improved antiviral effect. Our results show a potent and selective antiviral activity of TL peptides, indicating that the novel lipidated temporin-based antiviral agents could prove to be useful additions to current drugs in combatting rising drug resistance and epidemic/pandemic emergencies.