Franci, G. | Search bioRxiv

bioRxiv2022

A specific anti-IFITM2 antibody bars the way to SARS-CoV-2 entry into host cells.

The early steps of viral infection involve protein complexes and structural lipid rearrangements, which mark the characteristic strategies of each virus in entering permissive host cells. Human IFITM proteins have been described as inhibitors of a broad range of viruses. Despite their homology and functional redundancy, recently it has been surprisingly shown that SARS-CoV-2 is able to specifically hijack the IFITM2 protein. Here has been reported the characterization of a newly generated specific anti-IFITM2 mAb able to impair SARS-CoV-2 Spike protein internalization and, consequently, to reduce the SARS-CoV-2 cytopathic effects and syncytia formation. Importantly, as evidence of the more general involvement of IFITM2 in virus entry, the anti-IFITM2 mAb was able to efficiently reduce HSVs- and RSV-dependent cytopathic effects. Hence, IFITM proteins could be promising targets that can foster the development of biological antiviral molecules, or suggest additional therapeutic strategies for the treatment of viral infections. GRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2021

Outer membrane vesicles derived from Klebsiella pneumoniae are a driving force for horizontal gene transfer

Gram-negative bacteria release outer membrane vesicles (OMVs) into the extracellular environment. Recent studies recognized these vesicles as vectors to horizontal gene transfer, however the parameters that mediate OMVs transfer within bacterial communities remain unclear. The present study highlights for the first time the transfer of plasmids containing resistance genes via OMVs derived from Klebsiella pneumoniae (K. pneumoniae). This mechanism confers DNA protection and it is plasmid copy number dependent with a ratio of 3.6 time among high copy-number plasmid (pGR) versus low copy number plasmid (PRM) and the transformation efficiency was 3.6 times greater. Therefore, the DNA amount in the vesicular lumen and the efficacy of horizontal gene transfer was strictly dependent on the identity of the plasmid. Moreover, the role of K. pneumoniae-OMVs in interspecies transfer was described. The transfer ability was not related to the phylogenetic characteristics between the donor and the recipient species. K. pneumoniae-OMVs transferred plasmid to Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa and Burkholderia cepacia. These findings address the pivotal role of K. pneumoniae-OMVs as vectors for antimicrobial resistance genes spread, contributing to the development of antibiotic resistance in the microbial communities. Author summaryK. pneumoniae is an important opportunistic pathogen that affects several host districts, in particular respiratory and urinary tracts. Hospital-acquired K. pneumoniae infections lead to a 50% mortality rate correlated with rapid acquisition of antibiotic resistance. Currently, the increasing rate of antibiotic resistance among K. pneumoniae isolates is a major concern worldwide. The spread of multidrug-resistant K. pneumoniae strains renders current therapeutic options ineffective. Like all Gram-negative bacteria, K. pneumoniae secretes OMVs. OMVs are spherical structures, with a diameter between 50-250 nm, originating from the outer membrane. OMVs biogenesis allows bacteria to interact with the external environment, increasing bacterial survival under stressful conditions and regulating microbial interactions within bacterial communities. Few evidence recognized OMVs as vectors for horizontal gene transfer, contributing to the spread of resistance. In this scenario, the present study examines the potential role of K. pneumoniae-OMVs in inter- and intra-species diffusion of {beta}-lactam resistance.

microbiology↗

bioRxiv2021

DNA Mutations via Chern-Simons Current

We test the validity of a possible schematization of DNA structure and dynamics based on the Chern-Simons theory, that is a topological field theory mostly considered in the context of effective gravity theories. By means of the expectation value of the Wilson Loop, derived from this analogue gravity approach, we find the point-like curvature of genomic strings in KRAS human gene and COVID-19 sequences, correlating this curvature with the genetic mutations. The point-like curvature profile, obtained by means of the Chern-Simons currents, can be used to infer the position of the given mutations within the genetic string. Generally, mutations take place in the highest Chern-Simons current gradient locations and subsequent mutated sequences appear to have a smoother curvature than the initial ones, in agreement with a free energy minimization argument.

biophysics↗