Streptococcus agalactiae (group B streptococcus; GBS) is an important human pathogen causing pneumonia, sepsis and meningitis in neonates, as well as infections in pregnant women, immunocompromised individuals, and the elderly. For the future control of GBS-inflicted disease, GBS surface exposed proteins are particularly relevant as they may act as antigens for vaccine development and/or as serosubtype markers in epidemiological settings. Even so, the genes encoding some of the surface proteins established as serosubtype markers by antibody-based methods, like the R3 surface protein, are still unknown. Here, by examining a Norwegian GBS collection consisting of 140 strains, we find that R3 protein expression correlates with the presence of the gene sar5. By inducible expression of sar5 in an R3-negative bacterial strain we show that the sar5 gene product is specifically recognized by an R3 monoclonal antibody. With this we identify sar5 as the gene encoding the R3 surface protein, a serosubtype marker of hitherto unknown genetic origin.
Macrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage-associated CCL2 secretion, its influence on mesenchymal stem/progenitor cell (MSPC) chemotaxis, and in vivo cell recruitment using Ccr2 (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre-osteoblasts, MSPC) upregulated CCL2.
Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate.
Macrophages are versatile myeloid leukocytes with flexible cellular states to perform diverse tissue functions beyond immunity. This plasticity is however often hijacked by diseases to promote pathology. Scanning kinetics of macrophage states by single-cell transcriptomics and flow cytometry, we observed atopic dermatitis drastically exhausted a resident subtype S1.
Histatin 5 (Hst5) is a 24-amino-acid peptide naturally present in human saliva that has been proposed as a potential antifungal therapeutic. However, Hst5 is susceptible to degradation by secreted aspartyl proteases (Saps) produced by Candida albicans, which could limit its efficacy as a therapeutic. To better understand the role of the lysine residues of Hst5 in proteolysis by C.
