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\"This prosopography is a dictionary of all the characters and personal names found in the Epigrams of Marcus Valerius Martialis, containing nearly 1,000 comprehensive entries. Each of them compiles and analyses all the relevant information regarding the characters themselves, as well as the literary implications of their presence in Martial's poems. It is an indispensable tool for researchers and studients of Ancient History and Latin Literature.\"--Back cover.

Histidine is a versatile residue playing key roles in enzyme catalysis thanks to the chemistry of its imidazole group that can serve as nucleophile, general acid or base depending on its protonation state. In bacteria, signal transduction relies on two-component systems (TCS) which comprise a sensor histidine kinase (HK) containing a phosphorylatable catalytic His with phosphotransfer and phosphatase activities over an effector response regulator. Recently, a pH-gated model has been postulated to regulate the phosphatase activity of HisKA HKs based on the pH-dependent rotamer switch of the phosphorylatable His. Here, we have revisited this model from a structural and functional perspective on HK853–RR468 and EnvZ–OmpR TCS, the prototypical HisKA HKs. We have found that the rotamer of His is not influenced by the environmental pH, ruling out a pH-gated model and confirming that the chemistry of the His is responsible for the decrease in the phosphatase activity at acidic pH. Bacterial two-component systems are composed of a sensor histidine kinase (HK) and an effector response regulator and upon signal detection, the HK autophosphorylates a conserved His residue. Here the authors structurally and functionally characterise two HKs, HK853–RR468 and EnvZ–OmpR, and find that the rotamer of the phosphorylatable catalytic His is not influenced by the environmental pH, ruling out an earlier proposed pH-gated model.

Rotavirus is the leading agent causing acute gastroenteritis in young children, with the P[8] genotype accounting for more than 80% of infections in humans. The molecular bases for binding of the VP8* domain from P[8] VP4 spike protein to its cellular receptor, the secretory H type-1 antigen (Fuc-α1,2-Gal-β1,3-GlcNAc; H1), and to its precursor lacto-N-biose (Gal-β1,3-GlcNAc; LNB) have been determined. The resolution of P[8] VP8* crystal structures in complex with H1 antigen and LNB and site-directed mutagenesis experiments revealed that both glycans bind to the P[8] VP8* protein through a binding pocket shared with other members of the P[II] genogroup (i.e.: P[4], P[6] and P[19]). Our results show that the L-fucose moiety from H1 only displays indirect contacts with P[8] VP8*. However, the induced conformational changes in the LNB moiety increase the ligand affinity by two-fold, as measured by surface plasmon resonance (SPR), providing a molecular explanation for the different susceptibility to rotavirus infection between secretor and non-secretor individuals. The unexpected interaction of P[8] VP8* with LNB, a building block of type-1 human milk oligosaccharides, resulted in inhibition of rotavirus infection, highlighting the role and possible application of this disaccharide as an antiviral. While key amino acids in the H1/LNB binding pocket were highly conserved in members of the P[II] genogroup, differences were found in ligand affinities among distinct P[8] genetic lineages. The variation in affinities were explained by subtle structural differences induced by amino acid changes in the vicinity of the binding pocket, providing a fine-tuning mechanism for glycan binding in P[8] rotavirus.

Reversible protein phosphorylation is the most widespread regulatory mechanism in signal transduction. Autophosphorylation in a dimeric sensor histidine kinase is the first step in two-component signalling, the predominant signal-transduction device in bacteria. Despite being the most abundant sensor kinases in nature, the molecular bases of the histidine kinase autophosphorylation mechanism are still unknown. Furthermore, it has been demonstrated that autophosphorylation can occur in two directions, cis (intrasubunit) or trans (intersubunit) within the dimeric histidine kinase. Here, we present the crystal structure of the complete catalytic machinery of a chimeric histidine kinase. The structure shows an asymmetric histidine kinase dimer where one subunit is caught performing the autophosphorylation reaction. A structure-guided functional analysis on HK853 and EnvZ, two prototypical cis- and trans -phosphorylating histidine kinases, has allowed us to decipher the catalytic mechanism of histidine kinase autophosphorylation, which seems to be common independently of the reaction directionality. The phosphorylation of proteins is a common mechanism for signal transduction. Here, the authors present a structural analysis of a histidine kinase in the process of autophosphorylation, helping to elucidate the catalytic mechanism.

Quorum sensing (QS) is a mechanism of bacterial communication, coordinating important decisions depending on bacterial population. QS regulates important processes not only in bacterial behavior but also in genetic mobile elements and host-guest interactions. In Firmicutes , important processes such as competence development, sporulation, virulence, and biofilm formation are regulated by cytoplasmic quorum sensing (QS) receptors of the RRNPPA family using peptide-based communication. Although these systems regulate important processes in a variety of bacteria, their origin and diversification are poorly understood. Here, we integrate structural, genomic, and phylogenetic evidence to shed light on RRNPPA protein origin and diversification. The family is constituted by seven different subfamilies with different domain architectures and functions. Among these, three were found in Lactobacillales (Rgg, ComR, and PrgX) and four in Bacillales (AimR, NprR, PlcR, and Rap). The patterns of presence and the phylogeny of these proteins show that subfamilies diversified a long time ago, resulting in key structural and functional differences. The concordance between the distribution of subfamilies and the bacterial phylogeny was somewhat unexpected, since many of the subfamilies are very abundant in mobile genetic elements, such as phages, plasmids, and phage-plasmids. The existence of diverse propeptide architectures raises intriguing questions about their export and maturation. It also suggests the existence of diverse roles for the RRNPPA systems. Some systems encode multiple pheromones on the same propeptide or multiple similar propeptides, suggesting that they act as “chatterers.” Many others lack pheromone genes and may be “eavesdroppers.” Interestingly, AimR systems without associated propeptide genes were particularly abundant in chromosomal regions not classed as prophages, suggesting that either the bacterium or other mobile elements are eavesdropping on phage activity. IMPORTANCE Quorum sensing (QS) is a mechanism of bacterial communication, coordinating important decisions depending on bacterial population. QS regulates important processes not only in bacterial behavior but also in genetic mobile elements and host-guest interactions. In Firmicutes , the most important family of QS receptors is the RRNPPA family. Despite the importance of such systems in microbiology, we know little about RRNPPA origin and diversification. In this work, the combination of sequence analysis and structural biology allowed us to identify a very large number of novel systems but also to class of them in functional families and thereby study of their origin and functional diversification. Moreover, peptide pheromone analysis revealed new and intriguing mechanisms of communication, such as “eavesdropper” systems which only listen for the pheromone and “chatterers” that take control of the communication in their microenvironment.

Bacterial interactions are vital for adapting to changing environments, with quorum sensing (QS) systems playing a central role in coordinating behaviors through small signaling molecules. The RRNPPA family is the prevalent QS systems in Bacillota and mediating communication through secreted oligopeptides, which are processed into active pheromones by extracellular proteases. Notably, in several cases the propeptides show the presence of multiple putative pheromones within their sequences, which has been proposed as a mechanism to diversify peptide-receptor specificity and potentially facilitate new functions. However, neither the processes governing the maturation of propeptides containing multiple pheromones, nor their functional significance has been evaluated. Here, using 2 Rap systems from bacteriophages infecting Bacillus subtilis that exhibit different types of pheromone duplication in their propeptides, we investigate the maturation process and the molecular and functional activities of the produced pheromones. Our results reveal that distinct maturation processes generate multiple mature pheromones, which bind to receptors with varying affinities but produce identical structural and biological responses. These findings add additional layers in the complexity of QS communication and regulation, opening new possibilities for microbial social behaviors, highlighting the intricate nature of bacterial interactions and adaptation.

Endoglycosidase S (EndoS) is a bacterial endo-β-N-acetylglucosaminidase that specifically catalyzes the hydrolysis of the β-1,4 linkage between the first two N-acetylglucosamine residues of the biantennary complex-type N-linked glycans of IgG Fc regions. It is used for the chemoenzymatic synthesis of homogeneously glycosylated antibodies with improved therapeutic properties, but the molecular basis for its substrate specificity is unknown. Here, we report the crystal structure of the full-length EndoS in complex with its oligosaccharide G2 product. The glycoside hydrolase domain contains two well-defined asymmetric grooves that accommodate the complex-type N-linked glycan antennae near the active site. Several loops shape the glycan binding site, thereby governing the strict substrate specificity of EndoS. Comparing the arrangement of these loops within EndoS and related endoglycosidases, reveals distinct-binding site architectures that correlate with the respective glycan specificities, providing a basis for the bioengineering of endoglycosidases to tailor the chemoenzymatic synthesis of monoclonal antibodies. Endoglycosidase S only recognizes one particular type of glycan within IgG antibodies but the molecular basis for this high specificity is not fully understood. Here, the authors present the crystal structure of product-bound Endoglycosidase S, revealing the determinants for its glycan specificity.

The assembly of the gut resistome in early life is key to infant health. Specific perinatal factors such as cesarean section (C-section), antibiotic exposure and lack of breastfeeding practices are detrimental to proper microbial development and increase the antimicrobial resistance genes (ARGs). Using 265 gut longitudinal metagenomes from 66 mother-infant pairs, we investigated how perinatal factors influence the acquisition and dynamics of ARGs during the first year of life. Our findings reveal that Bifidobacterium plays a crucial role in modulating the infant resistome, with its high relative abundance being associated with a lower ARG load. Exclusive breastfeeding during the first month of life accelerates the reduction of ARGs and ensures a lower resistome burden at six months. Moreover, early breastfeeding cessation correlates with a higher ARG load, underscoring its long-term influence on microbial resilience. Importantly, we identify exclusive breastfeeding as a key strategy to mitigate the impact of C-section delivery on the infant gut resistome, counteracting the early-life antibiotic exposure associated with this procedure and the resulting resistance acquisition. By promoting a microbiome enriched in Bifidobacterium , breastfeeding may help suppress ARG-carrying taxa, reducing the risk of resistance dissemination. Our findings underscore the importance of breastfeeding as a natural intervention to shape the infant microbiome and resistome. Supporting breastfeeding through public health policies could help limit the spread of antimicrobial resistance in early life. In this work, authors show that exclusive breastfeeding reduces antimicrobial resistance gene burden in infants by promoting Bifidobacterium , counteracting C-section and antibiotic effects, and supporting healthy gut microbiome development during early life.

The large majority of histidine kinases (HKs) are multifunctional enzymes having autokinase, phosphotransfer and phosphatase activities, and most of these are transmembrane sensor proteins. Sensor HKs possess conserved cytoplasmic phosphorylation and ATP‐binding kinase domains. The different enzymatic activities require participation by one or both of these domains, implying the need for different conformational states. The catalytic domains are linked to the membrane through a coiled‐coil segment that sometimes includes other domains. We describe here the first crystal structure of the complete cytoplasmic region of a sensor HK, one from the thermophile Thermotoga maritima in complex with ADPβN at 1.9 Å resolution. The structure reveals previously unidentified functions for several conserved residues and reveals the relative disposition of domains in a state seemingly poised for phosphotransfer. The structure thereby inspires hypotheses for the mechanisms of autophosphorylation, phosphotransfer and response‐regulator dephosphorylation, and for signal transduction through the coiled‐coil segment. Mutational tests support the functional relevance of interdomain contacts.

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has since reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.