Search Results (150)

Species of the genus Streptococcus constitute important pathogens in human and veterinary medicine, being responsible for a wide spectrum of infections ranging from mild illnesses to severe invasive pathologies. Although β-lactams continue to be effective against most species, the global increase in resistance to macrolides, lincosamides, tetracyclines, and, in some cases, reduced susceptibility to penicillin represents a growing challenge for antimicrobial therapy. This review synthesizes the clinical and epidemiological landscape of antimicrobial resistance in the main Streptococcus species, including Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus dysgalactiae, and other species of clinical and veterinary relevance, addressing their epidemiological profiles, molecular mechanisms of resistance, and virulence factors. The main genetic determinants involved in resistance are discussed, namely the erm, mef, and tet genes, as well as the impact of alterations in penicillin-binding proteins, horizontal gene transfer, and biofilm formation on the persistence of infections and decreased therapeutic efficacy. Simultaneously, the main virulence factors are analyzed, including polysaccharide capsules, adhesins, toxins, extracellular enzymes, and immune response evasion mechanisms that contribute to the colonization, dissemination, and severity of infections. The importance of epidemiological and genomic surveillance, particularly through whole-genome sequencing, in monitoring the spread of resistant clones and identifying determinants of resistance and virulence is also highlighted. Taken together, the data highlight the need to strengthen programs for the rational use of antimicrobials, to promote integrated surveillance strategies from a One Health perspective, and to deepen knowledge about the interaction between antimicrobial resistance and virulence, in order to improve strategies for the prevention, diagnosis, and treatment of infections caused by Streptococcus spp. Full article

Background: Invasive Haemophilus influenzae type b (Hib) infection in children has become rare following the introduction of highly effective conjugate vaccines under national immunisation programmes. However, breakthrough invasive infections in fully immunised individuals can still occur. We report a case of invasive Hib infection presenting as epiglottitis and bacteraemia in a fully vaccinated 5-year-old boy in regional Queensland, Australia. Case presentation: The child, with no history of immunodeficiency, presented with a 3-day history of fever, progressive throat pain and reduced oral intake. Subsequent investigations revealed leukocytosis with left shift, markedly elevated C-reactive protein, and radiographic features consistent with epiglottitis. Blood culture grew H. influenzae type b. He was treated with intravenous cefotaxime and made a full recovery without complications. Immunological evaluation demonstrated Hib-specific IgG levels consistent with prior vaccinations, with normal immunoglobulin and lymphocyte profiles supporting the absence of immunodeficiency. Whole-genome sequencing of the isolate identified sequence type 6, a known circulating strain, and duplication of the capsule (cap-b) locus which has been associated with increased capsular polysaccharide production and reduced susceptibility to immune-mediated clearance. Conclusions: This case demonstrates that invasive Hib disease can occur in fully vaccinated, immunocompetent individuals and highlights the need for continued clinical vigilance. Pathogen-related factors, such as cap-b locus duplication, may reduce the effectiveness of the immune response. Despite this, immunisation can still confer partial protection, potentially contributing to the relatively mild clinical course. Ongoing surveillance and detailed microbiological investigation are essential to better understand and monitor vaccine breakthrough infections. Full article

While hydroxypropyl methylcellulose (HPMC) is a promising plant-based alternative to gelatin, its industrial application is limited by poor mechanical properties and high production costs. In this study, high-performance HPMC-based hard capsules were developed using an HPMC/gellan gum/ι-carrageenan ternary system. The formulation and preparation process were optimized via single-factor experiments, response surface methodology, and low-field nuclear magnetic resonance analysis. Scanning electron microscopy was applied to characterize the microstructural evolution during disintegration. The optimized capsules exhibited rapid disintegration within 15 min across four pH media and satisfied the requirements of the Chinese Pharmacopoeia (2025). Drug dissolution profiles using cefradine and ranitidine hydrochloride showed over 85% cumulative release within 30 min, with similarity factors higher than 50 relative to commercial gelatin capsules under the tested conditions. This work provides a feasible and low-cost strategy for the industrial production of plant-based capsules and promotes the high-value utilization of polysaccharide-based capsule materials. Full article

A new strategy to reduce the morbidity and mortality associated with invasive Streptococcus agalactiae (Streptococcus group B, GBS) diseases encompasses the development of vaccines. Candidate vaccines at different stages of clinical trials have been developed on capsular polysaccharides or protein antigens. We studied 328 GBS isolates identified using routine microbiological tests, latex-agglutination, and PCRs. The samples were categorised into two main groups: vaginal (69.2%) and extra-vaginal (30.8%). The molecular serotyping and target gene factors were determined using singleplex or multiplex PCRs. The most common serotypes identified were Ia (24.7%), V (22.0%), and III (18.9%). Serotypes I–V constituted a total of 89.0%. The non-typeable were 9.8%. The frequency of genes included in the recombinant GBS-NN (rib + bca) and GBS-NN2 (epsilon + alp2/3) vaccines were 54.3% and 40.8%. We noted a significant prevalence in the distribution of serotypes II, III, and non-typeable in GBS-NN, whereas serotypes Ia and IV were predominant in GBS-NN2. The serotype prevalence identified in our research was consistent with the data from our region and confirmed the predominance of the six main serotypes included in the hexavalent conjugated vaccine. We highlighted the importance of the combined administration of both protein vaccines, ensuring optimal vaccine coverage. Full article

Streptococcus pneumoniae resists host defenses through multiple surface factors, yet their specific contribution to protection against antimicrobial peptides remains incompletely understood. We examined the role of pneumococcal surface protein A (PspA) and the polysaccharide capsule in protection against the human defensin HNP-1. PspA conferred increased resistance to HNP-1-induced killing, shown by a decreased killing in the presence of purified recombinant PspA and an increased sensitivity when PspA was deficient from the surface of strains of two different genetic backgrounds or when anti-PspA antibody was present. The capsule also conferred protection against HNP-1, which was serotype-dependent, with type 2 protecting better than type 4, and free polysaccharides acted as decoys by sequestering HNP-1. Removal of surface PspA from capsule-deficient mutants revealed additive contributions of both factors to survival. Molecular docking analysis suggests a potential electrostatic interaction between PspA and HNP-1. These findings highlight the independent and complementary roles of PspA and the capsule in pneumococcal resistance to HNP-1 and provide novel insights that may inform future vaccine design and antimicrobial strategies. Full article

Background/Objective: Dietary polysaccharides are increasingly recognized as functional nutritional components that support human health through modulation of immune function. However, clinical evidence linking their intake to site-specific upper respiratory mucosal immune health in humans remains limited. This study investigated whether dietary β-1,3/1,6-glucan (SC-BG) from baker’s yeast may support upper respiratory mucosal immune health in healthy adults. Methods: Following in vitro assays on human dendritic cells (DCs), a randomized, double-blind, placebo-controlled parallel-group trial was performed in healthy adults (18–69 years) who consumed either SC-BG or placebo capsules for 12 weeks in Japan. The primary outcome was circulating DC activation. Secondary outcomes were mucosal immune markers including secretory immunoglobulin A (s-IgA) and lysozymes from site-specific mucosal swabs (posterior oropharyngeal wall/nasopharynx) and salivar, and self-perceived upper respiratory tract symptoms. Results: SC-BG increased CD80 expression in DCs in vitro. In the clinical trial, 40 participants were randomized (n = 20 per group), and 39 (SC-BG: n = 19, placebo: n = 20) were analyzed. At week 8, the SC-BG group showed higher cDC1 CD80 expression than placebo. SC-BG intake also attenuated declines in s-IgA levels in the posterior oropharyngeal wall and nasopharynx and increased salivary lysozyme concentrations. Participants receiving SC-BG reported fewer cumulative days with upper respiratory tract-related local and systemic symptoms. No test food-related adverse events were observed. Conclusions: These findings provide preliminary clinical and mechanistic observations suggesting that dietary SC-BG may enhance circulating cDC1 activation and may help support upper respiratory local mucosal immune health in healthy adults, highlighting the potential of dietary polysaccharides as functional nutritional strategies for maintaining immune resilience. Full article

H-NS (histone-like nucleoid-structuring protein) is a global regulator affecting diverse bacterial processes. This study aimed to elucidate the regulatory role of H-NS in the virulence of Klebsiella pneumoniae (K. pneumoniae), particularly in relation to capsule synthesis and anchoring. A clinically isolated ST11-KL64 strain of K. pneumoniae FK6741 with low virulence was used. The role of H-NS was evaluated using colony morphology, the string test, viscosity measurement, capsule quantification, transmission electron microscopy, growth curve, biofilm assay, a mouse infection model, transcriptomic analysis, and RT-qPCR. Deletion of hns converted FK6741 into a hypermucoid phenotype in the positive string test; capsule quantification and transmission electron microscopy (TEM) showed increased polysaccharide chains but a reduced and tightly bound capsule. The mutant was initially found to grow slowly but formed stronger biofilms. In vivo, it displayed reduced virulence but induced stronger inflammation. Molecular assays revealed upregulation of capsule synthesis genes (galF, wzi, wcaJ, and wzc) and downregulation of wabG, which is involved in capsule anchoring. H-NS represses capsule synthesis genes, limiting capsule formation in K. pneumoniae. In contrast, loss of H-NS downregulates wabG, a key gene involved in GalA-mediated capsule anchoring, resulting in unstable surface attachment and loss of capsular polysaccharides. Consequently, these unanchored polysaccharides fail to confer effective protection, resulting in reduced bacterial virulence. Full article

Klebsiella pneumoniae is a major opportunistic pathogen, where the polysaccharide capsule is traditionally recognized as a critical virulence determinant. However, its role in surface interactions and intracellular adaptation remains incompletely understood. Here, we combined phenotypic assays with physicochemical analyses to dissect the contribution of the capsule. A wza knockout mutant displayed enhanced biofilm formation, adhesion, and invasion of epithelial cells compared to the encapsulated strain. Zeta potential and hydrodynamic size measurements revealed that capsule absence increased surface negativity and exposure of adhesion structures, thereby promoting host–cell interactions. In contrast, intracellular survival assays demonstrated that the capsule conferred a clear advantage for persistence and replication. Together, our results support a dynamic model in which capsule expression imposes a trade-off: restricting early adhesion and biofilm development but favoring long-term intracellular survival. This trade-off model expands the understanding of capsule biology and may inform novel strategies to disrupt colonization or persistence in antibiotic-resistant K. pneumoniae. Full article

Background: Streptococcus pneumoniae (Spn) is a leading bacterial pathogen responsible for severe invasive diseases, including meningitis, sepsis, and pneumonia. Current pneumococcal vaccines, which are all based on capsular polysaccharide antigens, provide limited protection and are further compromised by post-vaccination serotype replacement. Pneumococcal surface protein A (PspA), a highly conserved virulence factor expressed across diverse serotypes, has emerged as a promising candidate antigen for novel protein-based vaccines. However, progress in this field has been hindered by the absence of standardized in vitro functional antibody assays. Methods: This study established a robust functional antibody detection method for PspA-based protein vaccines by modifying the conventional multiplex opsonophagocytic killing assay (MOPA), originally designed for polysaccharide-based vaccines. Using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) typing, a target strain panel was selected and developed to include representative strains from PspA Family 1-Clade 2 and Family 2-Clades 3 and 4. The MOPA protocol was optimized by extending the phagocytic reaction time to enhance sensitivity. Specificity was confirmed through recombinant PspA competitive inhibition assays. Results: The assay demonstrated high linearity (R² ≥ 0.98) between opsonophagocytic index (OI) and serum dilution, along with acceptable repeatability (CV ≤ 30%) and intermediate precision (CV ≤ 50%). Both preclinical and clinical serum samples exhibited potent bactericidal activity against diverse PspA families, independent of capsule type. Conclusions: This study provided a standardized framework to support the development and regulatory assessment of protein-based pneumococcal vaccines. Full article

Background/Objectives: Lansoprazole (LNS) is widely used to treat and prevent stomach and intestinal ulcers and as a proton pump inhibitor with low solubility and high permeability. Soluble soybean polysaccharides (SSPS) are well-known disintegrants in food processing but are rarely used in the pharmaceutical field. In this study, we included SSPS as a disintegrant in LNS formulation for pharmaceutical use to investigate the effect of SSPS on the characteristics, dissolution curve, and stability of LNS enteric coated pellets. Methods: The screening of multiple excipients in formulation optimized the release and stability profile of enteric LNS pellets. The final enteric coated LNS pellet containing SSPS were evaluated by LNS crystal form, release profile, and stability. Results: X-ray powder diffraction revealed that this new LNS pellet and commercial reference LNS pellet had similar crystal form by X-ray powder diffraction. Under both long-term and accelerated conditions, these new SSPS-containing LNS pellets had higher release rate and better acid resistance than reference marketed LNS pellets. Conclusions: Inclusion of SSPS in LNS formulation could increase the physicochemical stability of the enteric coated capsules after storage, providing the basis of SSPS for further development and utilization in pharmaceutical formulation as a promising excipient. Full article

Cryptococcus neoformans is a pathogenic yeast and the leading cause of cryptococcosis in humans. The calcium-calcineurin signaling pathway plays a central role in stress adaptation and virulence. To identify the uncharacterized regulators of fungal adaptation, we utilized an integrative systems biology approach, combining differential gene expression and network analysis using transcriptomic data from three key components of the calcium-calcineurin pathway (Cna1, Crz1, and Pmc1). Our workflow identified the CNAG_00522 gene product, which we designated tricalbin 1 (TCB1) due to its conserved calcium and lipid-binding C2 domains. TCB1 expression was found to be regulated by both Cna1 and Pmc1. Network analyses positioned Tcb1 as a bottleneck linking general stress response and cellular processes. Further molecular characterization confirmed that TCB1 expression is temperature and calcium-responsive. Functional studies of the tcb1Δ mutant revealed an enlarged capsule, increased GXM shedding, and enhanced viability under host-mimicking conditions. However, phenotypic screening demonstrated that the tcb1Δ mutant does not display sensitivity to cell wall or osmotic stressors, and TCB1 deletion did not attenuate virulence in the Tenebrio larval model. These findings suggest that TCB1 functions as a specialized regulator of fungal growth at 37 °C, capsule size, and GXM shedding. This study validates our integrative approach for guiding the identification of these complex regulators. Full article

Extracellular polymeric substances (EPSs) produced by actinomycetes of the genus Rhodococcus play crucial roles in their ecological success, metabolic versatility, and biotechnological value. This review summarizes existing studies of Rhodococcus EPSs, emphasizing the biochemical composition, functional attributes, and practical significance of EPSs, as well as their importance in biomedicine, bioremediation, and other applications (food industry, biomineralization) with respect to the EPS chemical composition and biological roles. Rhodococcus species synthesize complex EPSs composed primarily of polysaccharides, proteins and lipids that, like in other bacteria, support cell adhesion, aggregation, biofilm formation, and horizontal gene transfer (and can prevent exogenous DNA binding) and are highly important for resistance against toxicants and dissolution/assimilation of hydrophobic compounds. EPSs produced by different species of Rhodococcus exhibit diverse structures (soluble EPSs, loosely bound and tightly bound fractions, capsules, linear and branched chains, amorphous coils, rigid helices, mushroom-like structures, extracellular matrix, and a fibrillar structure with a sheet-like texture), leading to variations in their properties (rheological features, viscosity, flocculation, sorption abilities, compression, DNA binding, and interaction with hydrophobic substrates). Notably, the EPSs exhibit marked emulsifying and flocculating properties, contributing to their recognized role in bioremediation. Furthermore, EPSs possess antiviral, antibiofilm, anti-inflammatory, and anti-proliferating activities and high viscosity, which are valuable in terms of biomedical and food applications. Despite extensive industrial and environmental interest, the molecular regulation, biosynthetic pathways, and structural diversity of Rhodococcus EPSs remain insufficiently characterized. Advancing our understanding of these biopolymers could expand new applications in biomedicine, bioremediation, and biotechnology. Full article

The objective of this research was to combine three plant-derived polysaccharides, Lycium barbarum polysaccharides (LBP), peach gum polysaccharide (PGP), and citrus pectin (CP), with alginate (SA) to co-encapsulate probiotics and investigate the survival of cells during in vitro gastrointestinal digestion, storage, and application in yogurt. The incorporation of different polysaccharides into SA all improved the encapsulation efficiencies and surface regularities of probiotic capsules. Texture analysis showed that the PGP-incorporated microspheres exhibited the highest values for hardness, springiness, and resilience, while in terms of chewiness, the highest values were observed for the LBP and CP groups. In vitro gastrointestinal digestion analysis revealed that the incorporation of different polysaccharides all further enhanced the cell survival rates, and the SA: PGP group demonstrated superior probiotic protection with the minimal viability loss of only 0.40 log CFU/g after 6h digestion. During storage, SA: PGP group also exhibited the highest stability, which still maintained 7.7 Log CFU/g of viable cells at the end of 20 days storage, and after incorporation of SA: PGP into yogurt, 7.8 Log CFU/g of viable cells were still detected at the end of 21 days storage. Full article

Klebsiella pneumoniae is one of the most significant nosocomial pathogens and an important cause of human infections worldwide. The microorganism is capable of producing different capsular polysaccharides (CPSs), which are the primary receptors for capsule-specific K. pneumoniae bacteriophages encoding tailspike proteins (TSPs) with polysaccharide-degrading activity. In this study, the novel virulent Przondovirus phage Adeo was isolated and characterized. The phage was able to infect K. pneumoniae strain with a K39 capsular polysaccharide structure. The morphology, biological properties, stability, and genomic organization of Adeo were studied. Comparative genomic and phylogenetic analyses were performed to establish the relationship between the phage and other bacterial viruses. The gene encoding TSP Adeo_gp48 was identified and cloned. Recombinant depolymerase lacking the N-terminal part was expressed, purified, and formed an opaque zone of CPS depolymerization on the K39 K. pneumoniae bacterial lawns. The structural and phylogenetic similarities of Adeo’s TSP to other phage-encoded depolymerases were discussed. Full article

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development. Full article