Non-Escherichia coli Enterobacterales (NECE) can colonize the human gut and may present virulence determinants and phenotypes that represent severe heath concerns. Most information is available for virulent NECE strains, isolated from patients with an ongoing infection, while the commensal NECE population of healthy subjects is understudied. In this study, 32 NECE strains were isolated from the feces of 20 healthy adults. 16S rRNA gene sequencing and mass spectrometry attributed the isolates to Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter kobei, Citrobacter freundii, Citrobacter amalonaticus, Cronobacter sp., and Hafnia alvei, Morganella morganii, and Serratia liquefaciens. Multiplex PCR revealed that K. pneumoniae harbored virulence genes for adhesins (mrkD, ycfM, and kpn) and enterobactin (entB) and, in one case, also for yersiniabactin (ybtS, irp1, irp2, and fyuA). Virulence genes were less numerous in the other NECE species. Biofilm formation was spread across all the species, while curli and cellulose were mainly produced by Citrobacter and Enterobacter. Among the most common antibiotics, amoxicillin-clavulanic acid was the sole against which resistance was observed, only Klebsiella strains being susceptible. The NECE inhabiting the intestine of healthy subjects have traits that may pose a health threat, taking into account the possibility of horizontal gene transfer.

Escherichia coli may innocuously colonize the intestine of healthy subjects or may instigate infections in the gut or in other districts. This study investigated intestinal E. coli isolated from 20 healthy adults. Fifty-one strains were genotyped by molecular fingerprinting and analyzed for genetic and phenotypic traits, encompassing the profile of antibiotic resistance, biofilm production, the presence of surface structures (such as curli and cellulose), and their performance as recipients in conjugation experiments. A phylogroup classification and analysis of 34 virulence determinants, together with genes associated to the pks island (polyketide-peptide genotoxin colibactin) and conjugative elements, was performed. Most of the strains belonged to the phylogroups B1 and B2. The different phylogroups were separated in a principal coordinate space, considering both genetic and functional features, but not considering pulsed-field gel electrophoresis. Within the B2 and F strains, 12 shared the pattern of virulence genes with potential uropathogens. Forty-nine strains were sensitive to all the tested antibiotics. Strains similar to the potential pathogens innocuously inhabited the gut of healthy subjects. However, they may potentially act as etiologic agents of extra-intestinal infections and are susceptible to a wide range of antibiotics. Nevertheless, there is still the possibility to control infections with antibiotic therapy.

Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bioresorbable bone graft was designed and investigated for its ability to control antibiotic drug release in situ. This represents an ideal solution for the eradication or prevention of infection, while simultaneously repairing bone defects. Vancomycin hydrochloride and gentamicin sulfate, here considered for testing, were loaded into a previously developed and largely investigated hybrid bone-mimetic scaffold made of collagen fibers biomineralized with magnesium doped-hydroxyapatite (MgHA/Coll), which in the last ten years has widely demonstrated its effective potential in bone tissue regeneration. Here, we have explored whether it can be used as a controlled local delivery system for antibiotic drugs. An easy loading method was selected in order to be reproducible, quickly, in the operating room. The maintenance of the antibacterial efficiency of the released drugs and the biosafety of medicated scaffolds were assessed with microbiological and in vitro tests, which demonstrated that the MgHA/Coll scaffolds were safe and effective as a local delivery system for an extended duration therapy—promising results for the prevention of bone defect-related infections in orthopedic surgeries.

Metal–organic frameworks (MOFs) are a class of crystalline porous materials with outstanding physical and chemical properties that make them suitable candidates in many fields, such as catalysis, sensing, energy production, and drug delivery. By combining MOFs with polymeric substrates, advanced functional materials are devised with excellent potential for biomedical applications. In this research, Zeolitic Imidazolate Framework 8 (ZIF-8), a zinc-based MOF, was selected together with cellulose, an almost inexhaustible polymeric raw material produced by nature, to prepare cellulose/ZIF-8 composite flat sheets via an in-situ growing single-step method in aqueous media. The composite materials were characterized by several techniques (IR, XRD, SEM, TGA, ICP, and BET) and their antibacterial activity as well as their biocompatibility in a mammalian model system were investigated. The cellulose/ZIF-8 samples remarkably inhibited the growth of Gram-positive and Gram-negative reference strains, and, notably, they proved to be effective against clinical isolates of Staphylococcus epidermidis and Pseudomonas aeruginosa presenting different antibiotic resistance profiles. As these pathogens are of primary importance in skin diseases and in the delayed healing of wounds, and the cellulose/ZIF-8 composites met the requirements of biological safety, the herein materials reveal a great potential for use as gauze pads in the management of wound infections.

At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.

Isatin and its derivatives are important heterocycles found in nature and present in numerous bioactive compounds which possess various biological activities. Moreover, it is an essential building block in organic synthesis. The discovery of novel compounds active against human pathogenic bacteria and fungi is an urgent need, and the isatin may represent the suitable scaffold in the design of biologically relevant antimicrobials. A small library of 18 isatin hybrids was synthetized and evaluated for their antimicrobial potential on three reference strains: S. aureus, E. coli, both important human pathogens infamous for causing community- and hospital-acquired severe systemic infections; and C. albicans, responsible for devastating invasive infections, mainly in immunocompromised individuals. The study highlighted two lead compounds, 6k and 6m, endowed with inhibitory activity against S. aureus at very low concentrations (39.12 and 24.83 µg/mL, respectively).