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The editorial "Biology: The Open Road to a Theory of Life" discusses the vastness and complexity of the field of Biology, emphasizing the study of organisms at different scales of organization. It highlights the integration of information from various biological disciplines to deepen our understanding of life, evolution, and cellular processes. The journal Biology aims to advance scientific knowledge by exploring regularities and laws within different levels of life organization, with a focus on developing a theory of cellular life. The editorial encourages contributions that contribute to the theoretical advancement of Biology and the discovery of generalities within the study of life. [Extracted from the article]

Escherichia coli K1 isolates synthesize a polysialic acid (polySia) capsule, are components of the adult gastrointestinal microbiota and may cause lethal bacteraemia and meningitis if acquired maternally by newborn infants. We used a neonatal rat pup K1 infection model to establish that prompt administration of a selective capsule depolymerase reverses the bacteraemic state and prevents death of almost all pups. In untreated animals, bacteria colonize the gastrointestinal tract and gain entry to the blood compartment, where they express the non-O-acetylated form of polySia. The bacteria invade the major organs of the host; histological and histochemical analysis of brain sections revealed that at least some bacteria enter the central nervous system through the blood-cerebrospinal fluid barrier at the choroid plexus prior to colonization of the meninges. Once in this location, they cease expression of polySia. The unexpected abrogation of polySia, a factor associated with the pathogenesis of meningitis and essential for transit through the blood, suggests that the neuropathogen dispenses with its protective capsule once it has colonized protected niches. Thus, systemic infections due to encapsulated pathogens may be resolved by capsule depolymerization only if the enzyme modifies the bacteria whilst they are in the blood compartment.

Streptococcus pyogenes (group A streptococcus [GAS]), a catalase-negative gram-positive bacterium, is aerotolerant and survives [H.sub.2][O.sub.2] exposures that kill many catalase-positive bacteria. The molecular basis of the [H.sub.2][O.sub.2] resistance is poorly known. Here, we demonstrate that serotype M49 GAS lacking the Rgg regulator is more resistant to [H.sub.2][O.sub.2] and also decomposes more [H.sub.2][O.sub.2] than the parental strain. Subgenomic transcriptional profiling and genome-integrated green fluorescent protein reporters showed that a bicistronic operon, a homolog of the Streptococcus mutans ahpCF operon, is transcriptionally up-regulated in the absence of Rgg. Phenotypic assays with ahpCF operon knockouts demonstrated that the gene products decompose [H.sub.2][O.sub.2] and protect GAS against peroxide stress. In a murine intraperitoneal-infection model, Rgg deficiency increased the virulence of GAS, although in an ahpCF-independent manner. Rgg-mediated repression of [H.sub.2][O.sub.2] resistance is divergent from the previously characterized peroxide resistance repressor PerR. Moreover, Rgg-mediated repression of [H.sub.2][O.sub.2] resistance is inducible by cellular stresses of diverse natures--ethanol, organic hydroperoxide, and [H.sub.2][O.sub.2]. Rgg is thus identified as a novel sensoregulator of streptococcal [H.sub.2][O.sub.2] resistance with potential implications for the virulence of the catalase-negative GAS.

Transposon mutagenesis is a powerful technique for generating collections of insertion mutants for genetic studies. This paper describes how phage Mu DNA transposition complexes, transpososomes, can be exploited for gene delivery to efficiently introduce selectable markers to genomes of Gram-positive bacteria. Mu transpososomes were assembled in vitro with custom-designed mini-Mu transposons, concentrated, and electroporated into cells of three Gram-positive bacterial species: Staphylococcus aureus, Streptococcus pyogenes and Streptococcus suis. Within cells, the complexes reproduced an authentic DNA transposition reaction and integrated the delivered transposons into the bacterial genomes, yielding single-copy insertions. The integration efficiency among different species and strains of Gram-positive bacteria ranged from 1 x [10.sup.1] to 2 x [10.sup.4] c.f.u. [([micro]g introduced transposon DNA). sup.-1]. The strategy should be applicable to a variety of other Gram-positive species after initial optimization of certain key factors affecting transposon delivery, such as the preparation method of competent cells and physical parameters of electroporation. This study extends the scope of the Mu transpososome delivery-based genomic DNA integration strategy to Gram-positive bacteria. Thus, a straightforward generation of sizeable mutant banks is feasible for these bacteria, potentiating several types of genomic-level approaches for studies of a variety of important bacterial processes, such as pathogenicity.

Results reveal that in the majority of Streptococcus pyognes strains a glycoprotein-binding activity is detected in thyroglobulin, fetuin, asialofetuin and mucin glycoproteins. Data further indicate that the binding activity is regulated by the bacterial virulence factor regulating gene Mga.

Inhibition of bacterial adhesion was demonstrated in a study conducted on di-, tri-, and tetravalent dendritic galabiosides that inhibit hemagglutination by Streptococcus suis at nanomolar concentration. To form such compounds, coupling of galabiose derivatives to carrier molecules was initiated. Findings revealed the relationship between the number of galabiose units found in an inhibitor and inhibitory efficacy.

The role of the phage depolymerase in binding and degradation was investigated. Phage mutants that are specific for Escherichia coli bacteria that have a low level of K1 polysialic acid capsule were isolated. It was shown that these mutants have lost the cleaving activity of the phage endosialidase while retaining the binding activity. The results suggest that the polysaccharide-binding activity of the enzyme is necessary for phage infection, whereas the cleavage of the polysaccharide is required for penetration of the dense polysaccharide of wild-type bacteria but is inhibitory in the infection of bacteria with a sparsecapsule.

Abstract Background The expression of a neural crest stem cell marker, polysialic acid (polySia), and its main carrier, neural cell adhesion molecule (NCAM), have been detected in some malignant tumors with high metastatic activity and unfavorable prognosis, but the diagnostic and prognostic value of polySia-NCAM in neuroblastoma is unclear. Methods A tumor tissue microarray (TMA) of 36 paraffin-embedded neuroblastoma samples was utilized to detect polySia-NCAM expression with a polySia-binding fluorescent fusion protein, and polySia-NCAM expression was compared with clinical stage, age, MYCN amplification status, histology (INPC), and proliferation index (PI). Results PolySia-NCAM-positive neuroblastoma patients had more often metastases at diagnosis, and polySia-NCAM expression associated with advanced disease (P = 0.047). Most interestingly, absence of polySia-NCAM-expressing tumor cells in TMA samples, however, was a strong unfavorable prognostic factor for overall survival in advanced disease (P = 0.0004), especially when MYCN was not amplified. PolySia-NCAM-expressing bone marrow metastases were easily detected in smears, aspirates and biopsies. Conclusion PolySia-NCAM appears to be a new clinically significant molecular marker in neuroblastoma, hopefully with additional value in neuroblastoma risk stratification.

Abstract Background Flow cytometry based adherence assay is a potentially powerful but little used method in the study of bacterial binding to host structures. We have previously characterized a glycoprotein-binding activity in Streptococcus pyogenes called 'strepadhesin' binding to thyroglobulin, submaxillar mucin, fetuin and asialofetuin. We have identified surface-associated pullulanase (PulA) and cysteine protease (SpeB) as carriers of strepadhesin activity. In the present paper, we investigated the use of flow cytometry as a method to study the binding of Rgg, SpeB and PulA knock-out strains to cultured human epithelial cells. Results Streptococcal mutants were readily labelled with CFDA-SE and their binding to epithelial cells could be effectively studied by flow cytometry. A strain deficient in Rgg expression showed increased binding to the analyzed epithelial cell lines of various origin. Inactivation of SpeB had no effect on the adhesion, while PulA knock-out strains displayed decreased binding to the cell lines. Conclusion These results suggest that the flow cytometric assay is a valuable tool in the analysis of S. pyogenes adherence to host cells. It appears to be an efficient and sensitive tool for the characterization of interactions between the bacteria and the host at the molecular level. The results also suggest a role for Rgg regulated surface molecules, like PulA, in the adhesion of S. pyogenes to host cells.