Lipopolysaccharides and outer membrane proteins as main structures involved in complement evasion strategies of non-typhoidal Salmonella strains

Non-typhoidal Salmonella (NTS) infections pose a serious public health problem. In addition to the typical course of salmonellosis, an infection with Salmonella bacteria can often lead to parenteral infections and sepsis, which are particularly dangerous for children, the elderly and immunocompromised. Bacterial resistance to serum is a key virulence factor for the development of systemic infections. Salmonella, as an enterobacterial pathogen, has developed several mechanisms to escape and block the antibacterial effects of the complement system. In this review, we discuss the relevance of outer membrane polysaccharides to the complement evasion mechanisms of NTS strains. These include the influence of the overall length and density of the lipopolysaccharide molecules, modifications of the O-antigen lipopolysaccharide composition and the role of capsular polysaccharides in opsonization and protection of the outer membrane from the lytic action of complement. Additionally, we discuss specific outer membrane protein complement evasion mechanisms, such as recruitment of complement regula-tory proteins, blocking assembly of late complement components to form the membrane attack complex and the proteolytic cleavage of complement proteins.Peer reviewe

Supramolecular organization of liquid-crystal dimers-bis-cyanobiphenyl alkanes on HOPG by scanning tunneling microscopy

2D supramolecular organization of a series of six cyanobiphenyl bimesogens deposited on highly oriented pyrolytic graphite (HOPG) is studied by scanning tunneling microscopy (STM). The adsorbatesare 1,ω-bis(4-cyanobiphenyl-4’-yl)alkanes (CBnCB) with different length of their flexible alkyl spacer (containing 7 to 12 methylene groups). Microscopic investigations at the molecular resolution allow fordetailed analysis of the effect of the alkyl spacer length on the type and the extent of the resulting 2Dorganization. It has been demonstrated that bimesogens with shorter spacers (7 and 8 methylene units)organize in a similar manner characterized by the formation of two types of differently ordered monolayers: dense packed, wherein the molecules are oriented in one direction and ordered into parallel rows(layer structure), or less densely packed wherein they are organized into a chiral windmill-like structure. For derivatives with longer spacers (ranging from 9 to 12 methylene units) additional effect of parity of carbon atoms in the spacer (even versus odd) is observed. In this range of the spacer length even membered bimesogens are still organized in a typical layer structure. However, odd-membered dimers exhibit a much complex 2D supramolecular organization with a larger unit cell and a helical arrangement of the molecules. Careful comparison of this structure with the 3D structural data derived from the X-ray diffraction investigations of single crystals indicates that for these bimesogens a clear correlation exists between the observed complex 2D supramolecular organization in the monolayer and the organization in one of the crystallographic planes of the 3D nematic twist-bent phas

Impaired immunity and high attack rates caused by SARS-CoV-2 variants among vaccinated long-term care facility residents

Introduction: Long-term care facilities (LTCF) residents are at high risk for severe coronavirus disease 2019 (COVID-19), and therefore, COVID-19 vaccinations were prioritized for residents and personnel in Finland at the beginning of 2021. Methods: We investigated COVID-19 outbreaks in two LTCFs, where residents were once or twice vaccinated. After the outbreaks we measured immunoglobulin G (IgG) antibodies to severe acute respiratory syndrome coronavirus 2 spike glycoprotein, neutralizing antibody (NAb) titers, and cell-mediated immunity markers from residents and healthcare workers (HCWs). Results: In LTFC-1, the outbreak was caused by an Alpha variant (B.1.1.7) and the attack rate (AR) among once vaccinated residents was 23%. In LTCF-2 the outbreak was caused by a Beta variant (B.1.351). Its AR was 47% although all residents had received their second dose 1 month before the outbreak. We observed that vaccination had induced lower IgG concentrations, NAb titers and cell-mediated immune responses in residents compared to HCWs. Only 1/8 residents had NAb to the Beta variant after two vaccine doses. Conclusions: The vaccinated elderly remain susceptible to breakthrough infections caused by Alpha and Beta variants. The weaker vaccine response in the elderly needs to be addressed in vaccination protocols, while new variants capable of evading vaccine-induced immunity continue to emerge.Peer reviewe

Supramolecular organization of liquid-crystal dimers-bis-cyanobiphenyl alkanes on HOPG by scanning tunneling microscopy

2D supramolecular organization of a series of six cyanobiphenyl bimesogens deposited on highly oriented pyrolytic graphite (HOPG) is studied by scanning tunneling microscopy (STM). The adsorbatesare 1,ω-bis(4-cyanobiphenyl-4’-yl)alkanes (CBnCB) with different length of their flexible alkyl spacer (containing 7 to 12 methylene groups). Microscopic investigations at the molecular resolution allow fordetailed analysis of the effect of the alkyl spacer length on the type and the extent of the resulting 2Dorganization. It has been demonstrated that bimesogens with shorter spacers (7 and 8 methylene units)organize in a similar manner characterized by the formation of two types of differently ordered monolayers: dense packed, wherein the molecules are oriented in one direction and ordered into parallel rows(layer structure), or less densely packed wherein they are organized into a chiral windmill-like structure. For derivatives with longer spacers (ranging from 9 to 12 methylene units) additional effect of parity of carbon atoms in the spacer (even versus odd) is observed. In this range of the spacer length even membered bimesogens are still organized in a typical layer structure. However, odd-membered dimers exhibit a much complex 2D supramolecular organization with a larger unit cell and a helical arrangement of the molecules. Careful comparison of this structure with the 3D structural data derived from the X-ray diffraction investigations of single crystals indicates that for these bimesogens a clear correlation exists between the observed complex 2D supramolecular organization in the monolayer and the organization in one of the crystallographic planes of the 3D nematic twist-bent phas

A genome-wide DNA methylation signature for SETD1B-related syndrome

SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients

A genome-wide DNA methylation signature for SETD1B-related syndrome

SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients

In vitro adhesion, pilus expression, and in vivo amelioration of antibiotic-induced microbiota disturbance by Bifidobacterium spp. strains from fecal donors

Fecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.Peer reviewe