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Group B Streptococcus (GBS) is a major cause of neonatal morbidity and mortality. Serbia has not fully implemented preventive measures against GBS neonatal diseases. Therefore, we aimed to assess the maternal GBS colonisation and invasive neonatal disease rate, to reveal the trends of antimicrobial resistance and serotype distribution of GBS from various patient groups. Randomly selected non-invasive (n = 991) and all invasive GBS (n = 80) collected throughout Serbia from 2015 to 2020 were tested for antimicrobial susceptibility, capsular typing, and hvgA detection. Overall, 877/5621 (15.6%) pregnant women were colonised with GBS. Invasive GBS infections incidence in infants (0.18/1000 live births) showed a decreasing trend (0.3 to 0.1/1000 live births). Type III was overrepresented in infants with invasive infections (n = 35, 58.3%), whereas type V predominated among colonised adults (n = 224, 25.5%) and those with noninvasive (n = 37, 32.5%) and invasive infections (n = 8, 40%). The hypervirulent clone III/ST17 was highly associated with invasive infections (n = 28, 35%), particularly late-onset disease (n = 9, 47.4%), showing an increase from 12.3 to 14.8%. The GBS resistance to erythromycin and clindamycin was 26.7% and 22.1%, respectively, with an upward trend. The emergence of the hypervirulent clone III/ST17 and the escalation in GBS resistance highlight an urgent need for continuous monitoring of GBS infections.

Background. The capsular polysaccharide (CPS) is an important virulence factor and a vaccine target of the major neonatal pathogen group Streptococcus (GBS). Population studies revealed no strong correlation between CPS type and multilocus sequence typing (MLST) cluster, with the remarkable exception of the worldwide spread of hypervirulent GBS CC17, which were all until recently CPS type III. Methods. A total of 965 GBS strains from invasive infection isolated in France were CPS typed and the presence of the CC17-specific surface protein encoding gene hvgA gene was investigated. Three hvgA-positive GBS strains screened were surprisingly CPS type IV and thus further characterized by MLST typing, pulsed-field gel electrophoresis (PFGE), and whole genome sequencing. Results. MLST and PFGE demonstrated a capsular switching from CPS type III to IV within the highly homogeneous GBS CC17. Sequence analysis revealed that this capsular switch was due to the exchange of a 35.5-kb DNA fragment containing the entire cps operon. Conclusions. This work shows that GBS CCI7 hypervirulent strains have switched one of their main vaccine targets. Thus, continued surveillance of GBS population remains of the utmost importance during clinical trials of conjugate GBS vaccines.

Group streptococcus (GBS) is a leading neonatal pathogen and a growing cause of invasive disease in the elderly, with clinical manifestations such as pneumonia and sepsis. Despite its clinical importance, little is known about innate immunity against GBS in humans. Here, we analyze the role of human group IIA secreted phospholipase A₂(sPLA₂-IIA), a bactericidal enzyme induced during acute inflammation, in innate immunity against GBS. We show that clinical GBS isolates are highly sensitive to killing by sPLA₂-IIA but not by human antimicrobial peptides. Using transgenic mice that express human sPLA₂-IIA, we demonstrate that this enzyme is crucial for host protection against systemic infection and lung challenge by GBS. We found that acute sera from humans diagnosed with invasive GBS disease contain increased levels of sPLA₂-IIA compared with normal sera from healthy individuals, indicating that GBS induces an sPLA₂-IIA response in blood during human infection. We demonstrate that clinically relevant GBS strains are rapidly killed in these acute sera. We also demonstrate that the bactericidal effect is entirely due to sPLA₂-IIA, showing that sPLA₂-IIA might represent an important component of humoral innate immunity against GBS. Our data provide experimental and clinical evidence that sPLA₂-IIA protects humans against GBS infections.

We sought to determine whether pre-eclampsia, spontaneous preterm birth or the delivery of infants who are small for gestational age were associated with the presence of bacterial DNA in the human placenta. Here we show that there was no evidence for the presence of bacteria in the large majority of placental samples, from both complicated and uncomplicated pregnancies. Almost all signals were related either to the acquisition of bacteria during labour and delivery, or to contamination of laboratory reagents with bacterial DNA. The exception was Streptococcus agalactiae (group B Streptococcus), for which non-contaminant signals were detected in approximately 5% of samples collected before the onset of labour. We conclude that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome and that the human placenta does not have a microbiome, but it does represent a potential site of perinatal acquisition of S. agalactiae , a major cause of neonatal sepsis. The human placenta does not have a microbiota, suggesting that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome, but group B Streptococcus is found in approximately 5% of placental samples.

The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache 1 , 2 . Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year 3 – 5 . How pain and neuroimmune interactions impact meningeal antibacterial host defences are unclear. Here we show that Nav1.8 + nociceptors signal to immune cells in the meninges through the neuropeptide calcitonin gene-related peptide (CGRP) during infection. This neuroimmune axis inhibits host defences and exacerbates bacterial meningitis. Nociceptor neuron ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae . S.   pneumoniae activated nociceptors through its pore-forming toxin pneumolysin to release CGRP from nerve terminals. CGRP acted through receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment and dural antimicrobial defences. Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance in the meninges and brain. Therefore, bacteria hijack CGRP–RAMP1 signalling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis in the meninges can enhance host defences and potentially produce treatments for bacterial meningitis. Two Streptococcus spp. can utilize a neuropeptide (CGRP) and its receptor (RAMP1) on macrophages to promote brain invasion, a finding that may help the development of therapies for bacterial meningitis.

Key Points The blood–central nervous system (CNS) barriers are tight and protect the brain parenchyma from insults, including those of infectious origin. This barrier function is due to the presence of tight junctions between the endothelial cells of the brain. The formation of these junctions is the consequence of interactions inside the neurovascular unit. There are two blood–CNS barriers that can potentially be circumvented by bacterial pathogens: the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). The BCSFB corresponds to the choroid plexuses and the microvessels of the leptomeninges. Bacteria can invade the meninges from the bloodstream through the choroid plexuses or directly through the microvessels of the leptomeninges and/or the brain parenchyma. In the case of crossing from parenchyma vessels, bacteria are drained to the subarachnoid space through the glymphatic pathway. Regardless of the site of crossing, meningeal invasion requires the crossing of two cellular barriers: an endothelial monolayer (in the choroid plexus or in the brain parenchyma and/or leptomeninges) followed by an epithelial monolayer (the choroid plexus ependyma, or the leptomeningeal monolayer of the pia mater or of a subarachnoid trabecula). A limited number of blood-borne bacteria can cross the blood–CNS barriers and cause meningitis. The extracellular pathogens that are involved are usually Neisseria meningitidis , Streptococcus pneumoniae or, in newborns, group B Streptococcus and Escherichia coli K1. Regardless of the mechanisms that are used to invade the meninges from the bloodstream, the level of bacteraemia plays a key part in meningeal tropism. The extracellular bacteria interact directly with the blood–CNS barriers. N. meningitidis is believed to cross the blood–CNS barriers by interacting with the leptomeninges and/or brain microvessels, and to open intercellular junctions following signals that are induced by the adhesion of bacteria to the endothelial cells. S. pneumoniae invades the meninges following interaction with the brain microvessels and is believed to transcytose through the endothelial cells following interactions with several host cell receptors. E. coli is believed to transcytose through endothelial cells, to have several attributes that enable it to adhere to endothelial cells and to induce signalling events that lead to bacterial invasion. Bacteria have to overcome many obstacles to invade the meninges from the bloodstream. This Review considers how extracellular pathogens such as Neisseria meningitides and Streptococcus pneumoniae bypass the blood–brain barriers, the understanding of which may lead to improved methods for delivering drugs into the brain. The blood–brain barrier, which is one of the tightest barriers in the body, protects the brain from insults, such as infections. Indeed, only a few of the numerous blood-borne bacteria can cross the blood–brain barrier to cause meningitis. In this Review, we focus on invasive extracellular pathogens, such as Neisseria meningitidis , Streptococcus pneumoniae , group B Streptococcus and Escherichia coli , to review the obstacles that bacteria have to overcome in order to invade the meninges from the bloodstream, and the specific skills they have developed to bypass the blood–brain barrier. The medical importance of understanding how these barriers can be circumvented is underlined by the fact that we need to improve drug delivery into the brain.

Group B Streptococcus (GBS, Streptococcus agalactiae ) is a leading cause of invasive disease in neonates, pregnant women, elderly, and immunocompromised individuals. The epidemiology of invasive GBS disease remains poorly documented in small, isolated populations such as the Faroe Islands. This nationwide study assessed invasive GBS cases from 2009 to 2024 in the Faroe Islands. A total of 42 GBS cases were identified. Serotyping was performed using phenotypic assays, with in silico whole-genome sequencing (WGS) based serotype confirmation available for 15 isolates collected between 2020 and 2024. Multilocus sequence typing (MLST), antimicrobial resistance profiling, and virulence gene were also performed. GBS incidence showed an increasing trend over the 15-year period, with the average annual incidence increasing from 3.69 (2009–2018) to 7.47 (2019–2024) per 100,000 population. Predominant serotypes were II, V, Ib, and Ia. All isolates carried genes coding for Alp-family proteins, which are immunogenic targets that may meaningfully influence the effectiveness of future GBS vaccines. MLST revealed a predominance of clonal complex (CC) 12, followed by CC452, CC1, and CC23. Phenotypic testing showed that all isolates were susceptible to penicillin, while four displayed resistance to erythromycin and clindamycin, with two carrying the erm(A) gene. Virulence genes including pilus islands ( PI ), cfb , sodA , and srr1 were detected. This study establishes a genomic and epidemiological baseline for invasive GBS in the Faroe Islands, highlighting an increase in incidence, data suggesting the likely efficacy of future GBS vaccine candidates, and preserved penicillin susceptibility. Continued genomic surveillance will be essential for informing public health and vaccine policy in small and remote populations.

•Largest GBS genome sequence sample of Chinese infants.•Baseline data for GBS surveillance and vaccine impact evaluation. Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively.“ The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.

Group B Streptococcus (GBS), a causative agent of newborn infection, colonizes the digestive system and genitourinary tracts of pregnant women. The aim of this study was to assess the incidence of GBS capsular serotypes, virulence genes, and antibiotic resistance in pregnant women at a prominent maternity hospital in Shahrekord, Chaharmahal and Bakhtiari. From January to July 2022, a total of 370 vaginal swabs were collected from women who were from 28 to 38 weeks pregnant. These swabs were used to identify Streptococcus agalactiae using PCR and culture technique. The capsular serotype of Streptococcus agalactiae isolates, antibiotic resistance and virulence genes distribution were determined through disk diffusion and multiplex PCR methods. mong 370 vaginal samples, 36 (9.72%) isolates were detected by culture and molecular methods, that type III (37.83%) and type V (32.43%) were the most frequent capsular serotypes, and all isolates harbored atr , and dltS genes. Moreover, the most frequent antibiotic resistance genes (62.16%) in the isolates is was related to tetO and ermA. All isolates were resistant to penicillin (100%), and the highest antibiotic susceptibility was found against linezolid (81%). Our study revealed a high rate of antibiotic resistance in Streptococcus agalactiae isolates, that molecular method was reliable approach for identification of infection and detection of harbored resistance genes. However, more studies are required to identification of effective antibiotics against infections and prevention of resistance in pregnant women.

Developing a therapeutic target for bacterial disease is challenging. In silico subtractive genomics methodology offer a promising alternative to traditional drug discovery methods. Streptococcus agalactiae infections depend on two crucial criteria: drug-resistance and the existence of virulence factors. It is essential to underline that S. agalactiae strains have emerged to be resistant to several drugs. Hence, there is a need for research on novel drugs and techniques that are potent, economical, productive, and dependable to combat S. agalactiae infections. In this study advanced computational techniques were exploited to examine potential druggable targets exclusive to this pathogen. Our study uncovered 200 non-homologous proteins in S. agalactiae serotype V (Strain ATCC BAA-611/ 2603 V/R) and identified 68 essential proteins indispensable for the bacterium's survival. Therefore, these 68 proteins are potential targets for drug development. Subcellular localization analysis unveiled that the pathogen's cytoplasmic membrane contained essential proteins among these vital non-homologous proteins. On the other hand, based on virulent protein predictions, six proteins were seen to be virulent. Among these, we prioritized two proteins (Sensor protein LytS and Galactosyl transferase CpsE which are exclusively found in S. agalactiae) as potential druggable targets and selected them for further structural investigation. The proteins chosen could serve as a foundation for the identification of a promising therapeutic compound that has the potential to neutralize these enzymatic proteins, thereby contributing to the reduction of risks linked to the drug-resistant S. agalactiae.