WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Antimicrobial and Antibiofilm Properties of Graphene Oxide on Enterococcus faecalis

The aim of this study was to evaluate the antibacterial properties of graphene oxide (GO) against Enterococcus faecalis in vitro conditions and when used to coat dentin surface to prevent E. faecalis adhesion. The ATCC strain of E. faecalis 29212 has been used to perform a viability test. The pellet was suspended in ultrapure water, NaCl, PBS buffer, CaCl2 and MgCl2, Luria−Bertani broth solutions. The viability was evaluated by the colony forming unit counting method. Atomic force microscopy images and the measure of surface zeta potential variation were analyzed. Dentin discs were covered with a film of GO (n = 15) or were not treated (n = 15). Bacterial suspension was added to each sample of dentine discs and microbial counts were calculated. Statistically significant differences between two groups were assessed by a two-tailed unpaired t-test. Bacteria cell morphology was investigated with scanning electron microscopy. The highest growth inhibition was obtained in ddH2O and CaCl2 solution while, in PBS and NaCl, GO had poor antibacterial efficacy with a growth enhancing effect in the latter. GO on dentin discs demonstrated high antibacterial activity. GO film has demonstrated acceptable adhesion properties to root dentin and a role in the inhibition of bacterial film proliferation and biofilm formation

Affinity capillary electrophoresis study of the linkage existing between proton and zinc ion binding to bacitracin A1

Measurements by capillary electrophoresis (CE) of bacitracin A(1) effective mobility at different pH values permitted to estimate the five acidic dissociation constants and the Stokes radii at different protonation stages of the macrocyclic dodecapeptide. The pK(a) values were 3.6 and 4.4 for the two carboxylic groups of the lateral chains of D-Asp-11 and D-Glu-4, respectively, 6.4 for the aza-atom of the imidazole ring of His-10, 7.6 for the amino group of N-terminal Ile-1 and 9.7 for the delta-amino group of D-Orn-7, very close to the values obtained by other researchers by titration experiments. In agreement with a rigid macrocyclic structure the Stokes radii of different protonated forms ranged only between 14.3 and 14.8 Angstrom. Best fitting procedures performed on experimental mobility measured at two different pH values (5.50 and 6.72) in the presence of increasing Zn+2 concentration allowed confirming the model that assumes the binding of Zn+2 to P-0 peptide form with a 1.5 x 10(3) M-1 intrinsic association constant. Following to Zn+2 binding, the pK(a) of the amino group of N-terminal Ile-1 is shifted from 7.6 to 5.9 and the Stokes radius is reduced of about 3 Angstrom. The mean charge of the bacitracin A(1)-Zn+2 complex resulted +1.67 and +1.12 at pH 5.50 and 6.72, respectively. These results suggest that the amino group of N-terminal Ile-1 is not essential for Zn+2 binding

Different binding thermodynamics of Ni+2, Cu+2 and Zn+2 to bacitracin A1 determined by capillary electrophoresis

Thermodynamics of the binding of Ni2+, Cu2+ and Zn2+ to bacitracin A(1) was studied by capillary electrophoresis measuring the peptide effective mobility at different pH in the presence of increasing concentration of the three ligands. The affinity follows the order Ni2+ > Cu2+ > Zn2+, with association constant values of (2.3+/- 0.1) X 10(4), (4.9+/-0.2) x 10(3), and (1.5 +/- 0.1) x 10(3) m(-1), respectively. The only model able to rationalize mobility data implies that metal ion binds to the P-O peptide form. Moreover, mobility values indicated a change of bacitracin A(1) acidic properties on Ni2+ and Cu2+ binding, with a shift of the pK(a), of N-terminal Ile-1 from 7.6 to about 5 and of the pK(a) of the delta-amino group Of D-Orn-7 from 9.7 to about 7. Even though on Zn2+ binding a shift of the N-terminal Ile-1 pK(a) was observed, restrictions in the pH range suitable for investigation, due to precipitation phenomena, did not allow establish if the shift Of D-Orn-7 lateral chain pK(a) also occurred. Nonetheless, if present, the shift should be limited to the 7.8-9.7 range. Mobility data indicated that the Stokes radius of the complexes is ca. 3 Angstrom lower than that of the free peptide. The present results indicate that metal-ion binding to bacitracin A(1) is more complex than previously assumed

Capillary electrophoretic study of the binding of Zn(II) ion to bacitracin A1 in water-2,2,2-trifluoroethanol

Binding of Zn2+ to bacitracin A(1) was studied by capillary electrophoresis in water/2,2,2-trifluoroethanol (70/30 v/v) at different apparent pH values in order to estimate the association constant of metal, the acidic dissociation constants and the Stokes radii of both free and bounded peptide in apolar environment. The Stokes radii of the free peptide species were compared with those in aqueous solution, as obtained in a recent study performed by our group, indicating that apolar environment stabilizes bacitracin A(1) in a conformational structure with the lateral chain of apolar amino acids exposed on the external surface. This conformation of the macrocyclic dodecapeptide is ready to interact with Zn2+ ion, as pointed out by the strong increase of the association constant measured in water/2,2,2-trifluoroethanol with respect to the value obtained in aqueous solution. In addition, whereas Zn2+ ion binding in aqueous solution provides a sensible reduction of peptide Stokes radius, no sensible variations following to ion binding were observed in hydro-organic solution. The present results suggest that the apolar environment, rather than the metal ion binding, could be responsible for the conformational transition that brings bacitracin A(1) towards its biologically active structure*

Characterization of the human salivary basic proline-rich protein complex by a proteomic approach

Thirteen samples of human normal whole saliva were analyzed by RP-HPLC-ESI-MS and MALDI-TOF-MS to investigate the basic proline-rich protein complex. Between known basic-PRPs the P-B, P-C (or IB-8b), P-D (or IB-5), P-E (or IB-9), P-F (or IB-8), P-H (or IB-4), IB-6,II-2, IB-1, and IB-8a glucosylated were identified, whereas the II-1, IB-7, PA, and D1-A peptides were not detected. Some detected masses not attributable to known basic-PRPs were putatively ascribed to II-2 and IB-1 nonphosphorylated, II-2 and IB-1 missing the C-terminal arginine residue, and the 1-62 fragment of IB-6, named P-J peptide. A correlation matrix analysis revealed a cluster of correlation among all the basic PRF's (apart from the P-B peptide) which is in agreement with their common parotid origin

Risk of invasive fungal infection in patients affected by acute promyelocytic leukaemia. A report by the SEIFEM-D registry

Patients with acute promyelocytic leukaemia (APL) are usually considered at lower risk for developing an infectious complication (Girmenia et al, 2003), principally because current treatments are mainly based on the induction of myeloid differentiation rather than the highly myeloablative properties of standard chemotherapy used in patients with acute myeloid leukaemia (AML). This prospective study, conducted in 33 locations throughout Italy, evaluated the incidence of invasive fungal infection (IFI) and the clinical characteristics in patients with APL compared to patients affected by other AML subtypes treated with intensive chemotherapy