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Group B Streptococcus (GBS) is a major human and animal pathogen that threatens public health and food security. Spill-over and spill-back between host species is possible due to adaptation and amplification of GBS in new niches but the evolutionary and functional mechanisms underpinning those phenomena are poorly known. Based on analysis of 1,254 curated genomes from all major GBS host species and six continents, we found that the global GBS population comprises host-generalist, host-adapted and host-restricted sublineages, which are found across host groups, preferentially within one host group, or exclusively within one host group, respectively, and show distinct levels of recombination. Strikingly, the association of GBS genomes with the three major host groups (humans, cattle, fish) is driven by a single accessory gene cluster per host, regardless of sublineage or the breadth of host spectrum. Moreover, those gene clusters are shared with other streptococcal species occupying the same niche and are functionally relevant for host tropism. Our findings demonstrate (1) the heterogeneity of genome plasticity within a bacterial species of public health importance, enabling the identification of high-risk clones; (2) the contribution of inter-species gene transmission to the evolution of GBS; and (3) the importance of considering the role of animal hosts, and the accessory gene pool associated with their microbiota, in the evolution of multi-host bacterial pathogens. Collectively, these phenomena may explain the adaptation and clonal expansion of GBS in animal reservoirs and the risk of spill-over and spill-back between animals and humans.
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Genoma Bacteriano , Infecções Estreptocócicas , Streptococcus agalactiae , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/genética , Animais , Humanos , Bovinos , Especificidade de Hospedeiro/genética , Genômica , Peixes/microbiologia , FilogeniaRESUMO
BACKGROUND: Nosocomial infections pose a considerable risk to patients who are susceptible, and this is particularly acute in intensive care units when hospital-associated bacteria are endemic. During the first wave of the COVID-19 pandemic, the surge of patients presented a significant obstacle to the effectiveness of infection control measures. We aimed to assess the risks and extent of nosocomial pathogen transmission under a high patient burden by designing a novel bacterial pan-pathogen deep-sequencing approach that could be integrated with standard clinical surveillance and diagnostics workflows. METHODS: We did a prospective cohort study in a region of northern Italy that was severely affected by the first wave of the COVID-19 pandemic. Inpatients on both ordinary and intensive care unit (ICU) wards at the San Matteo hospital, Pavia were sampled on multiple occasions to identify bacterial pathogens from respiratory, nasal, and rectal samples. Diagnostic samples collected between April 7 and May 10, 2020 were cultured on six different selective media designed to enrich for Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae, and DNA from each plate with positive growth was deep sequenced en masse. We used mSWEEP and mGEMS to bin sequencing reads by sequence cluster for each species, followed by mapping with snippy to generate high quality alignments. Antimicrobial resistance genes were detected by use of ARIBA and CARD. Estimates of hospital transmission were obtained from pairwise bacterial single nucleotide polymorphism distances, partitioned by within-patient and between-patient samples. Finally, we compared the accuracy of our binned Acinetobacter baumannii genomes with those obtained by single colony whole-genome sequencing of isolates from the same hospital. FINDINGS: We recruited patients from March 1 to May 7, 2020. The pathogen population among the patients was large and diverse, with 2148 species detections overall among the 2418 sequenced samples from the 256 patients. In total, 55 sequence clusters from key pathogen species were detected at least five times. The antimicrobial resistance gene prevalence was correspondingly high, with key carbapenemase and extended spectrum ß-lactamase genes detected in at least 50 (40%) of 125 patients in ICUs. Using high-resolution mapping to infer transmission, we established that hospital transmission was likely to be a significant mode of acquisition for each of the pathogen species. Finally, comparison with single colony Acinetobacter baumannii genomes showed that the resolution offered by deep sequencing was equivalent to single-colony sequencing, with the additional benefit of detection of co-colonisation of highly similar strains. INTERPRETATION: Our study shows that a culture-based deep-sequencing approach is a possible route towards improving future pathogen surveillance and infection control at hospitals. Future studies should be designed to directly compare the accuracy, cost, and feasibility of culture-based deep sequencing with single colony whole-genome sequencing on a range of bacterial species. FUNDING: Wellcome Trust, European Research Council, Academy of Finland Flagship program, Trond Mohn Foundation, and Research Council of Norway.
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Defining the population structure of a pathogen is a key part of epidemiology, as genomically related isolates are likely to share key clinical features such as antimicrobial resistance profiles and invasiveness. Multiple different methods are currently used to cluster together closely related genomes, potentially leading to inconsistency between studies. Here, we use a global dataset of 26 306 Streptococcus pneumoniae genomes to compare four clustering methods: gene-by-gene seven-locus MLST, core genome MLST (cgMLST)-based hierarchical clustering (HierCC) assignments, life identification number (LIN) barcoding and k-mer-based PopPUNK clustering (known as GPSCs in this species). We compare the clustering results with phylogenetic and pan-genome analyses to assess their relationship with genome diversity and evolution, as we would expect a good clustering method to form a single monophyletic cluster that has high within-cluster similarity of genomic content. We show that the four methods are generally able to accurately reflect the population structure based on these metrics and that the methods were broadly consistent with each other. We investigated further to study the discrepancies in clusters. The greatest concordance was seen between LIN barcoding and HierCC (adjusted mutual information score=0.950), which was expected given that both methods utilize cgMLST, but have different methods for defining an individual cluster and different core genome schema. However, the existence of differences between the two methods shows that the selection of a core genome schema can introduce inconsistencies between studies. GPSC and HierCC assignments were also highly concordant (AMI=0.946), showing that k-mer-based methods which use the whole genome and do not require the careful selection of a core genome schema are just as effective at representing the population structure. Additionally, where there were differences in clustering between these methods, this could be explained by differences in the accessory genome that were not identified in cgMLST. We conclude that for S. pneumoniae, standardized and stable nomenclature is important as the number of genomes available expands. Furthermore, the research community should transition away from seven-locus MLST, whilst cgMLST, GPSC and LIN assignments should be used more widely. However, to allow for easy comparison between studies and to make previous literature relevant, the reporting of multiple clustering names should be standardized within the research.
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Genoma Bacteriano , Tipagem de Sequências Multilocus , Filogenia , Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/classificação , Tipagem de Sequências Multilocus/métodos , Análise por Conglomerados , Humanos , Genômica/métodosRESUMO
Studies of bacterial adaptation and evolution are hampered by the difficulty of measuring traits such as virulence, drug resistance, and transmissibility in large populations. In contrast, it is now feasible to obtain high-quality complete assemblies of many bacterial genomes thanks to scalable high-accuracy long-read sequencing technologies. To exploit this opportunity, we introduce a phenotype- and alignment-free method for discovering coselected and epistatically interacting genomic variation from genome assemblies covering both core and accessory parts of genomes. Our approach uses a compact colored de Bruijn graph to approximate the intragenome distances between pairs of loci for a collection of bacterial genomes to account for the impacts of linkage disequilibrium (LD). We demonstrate the versatility of our approach to efficiently identify associations between loci linked with drug resistance and adaptation to the hospital niche in the major human bacterial pathogens Streptococcus pneumoniae and Enterococcus faecalis.
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Enterococcus faecalis , Epistasia Genética , Genoma Bacteriano , Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Enterococcus faecalis/genética , Desequilíbrio de Ligação , Humanos , Genômica/métodosRESUMO
BACKGROUND: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan. METHODS: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates. RESULTS: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively. CONCLUSION: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes.
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Objectives: Certain Group B Streptococcus (GBS) genotypes are associated with invasive disease in neonates. We conducted a comparative genomic analysis of GBS isolates from neonatal disease and maternal carriage in the Netherlands to determine distribution of genetic markers between the two host groups. Methods: Whole genome sequencing was used to characterise 685 neonatal invasive isolates (2006-2021) and 733 maternal carriage isolates (2017-2021) collected in the Netherlands. Results: Clonal complex (CC) 17 and serotype III were significantly more common in disease while carriage isolates were associated with serotypes II, IV, V as well as CC1. Previously reported CC17-A1 sub-lineage was dominant among disease isolates and significantly less common in carriage. The phiStag1 phage, previously associated with expansion of invasive CC17 isolates in the Netherlands, was more common among disease isolates compared to carriage isolates overall, however it was equally distributed between CC17 isolates from carriage and disease. Prevalence of antimicrobial resistance genes was overall lower in disease compared to carriage isolates, but increased significantly over time, mediated by rise in prevalence of a multidrug resistance element ICESag37 among disease isolates. Conclusion: There is a stable association between certain GBS genotypes and invasive disease, which suggests opportunities for developing more precise disease prevention strategies based on GBS targeted screening. In contrast, GBS mobile genetic elements appear less likely to be correlated with carriage or disease, and instead are associated with clonal expansion events across the GBS population.
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Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.
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Aptidão Genética , Mapeamento Geográfico , Streptococcus pneumoniae , Humanos , Aptidão Genética/efeitos dos fármacos , Aptidão Genética/genética , Genoma Bacteriano/genética , Resistência às Penicilinas/efeitos dos fármacos , Resistência às Penicilinas/genética , Penicilinas/farmacologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/transmissão , Vacinas Pneumocócicas/imunologia , Sorogrupo , África do Sul/epidemiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Vacinas Conjugadas/imunologia , Vacina Pneumocócica Conjugada Heptavalente/imunologia , LocomoçãoRESUMO
The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% (n = 161 positive/499 participants). During NPIs, this fell to 19% (n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% (n = 15/46) [compared to NPIs period, χ2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% (n = 127/470) in 2019/2020 to 19% during the NPI period (n = 44/228) in 2020/2021 [χ2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% (n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCEStreptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon.
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COVID-19 , Portador Sadio , Infecções por Haemophilus , Haemophilus influenzae , Nasofaringe , Infecções Pneumocócicas , SARS-CoV-2 , Streptococcus pneumoniae , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pré-Escolar , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , SARS-CoV-2/isolamento & purificação , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/microbiologia , Masculino , Feminino , Streptococcus pneumoniae/isolamento & purificação , Estudos Transversais , Lactente , Haemophilus influenzae/isolamento & purificação , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/prevenção & controle , Infecções por Haemophilus/microbiologia , Nasofaringe/microbiologia , Nasofaringe/virologia , Reino Unido/epidemiologia , PrevalênciaRESUMO
BACKGROUND: Escherichia coli and Klebsiella pneumoniae rank among the primary bacterial culprits in neonatal infections and fatalities in sub-Saharan Africa. This study characterized the phenotypic and genotypic features of E coli and K pneumoniae in a labor ward in Yaoundé, Cameroon. METHODS: A prospective and cross-sectional study spanning 5months, from February 21, 2022 to June 30, 2022. Rectovaginal swabs were obtained from expectant mothers, and nasopharyngeal swabs were collected from their babies. Hand swabs of health care workers and environmental samples were also collected. The samples were cultured on eosin methylene blue agar. Extended-spectrum ß-lactamase (ESBL) production was assessed using CHROMAgar ESBL and the double-disk synergy test. A polymerase chain reaction was employed to detect ß-lactamase genes. RESULTS: A total of 93 mothers and 90 neonates were collected. Almost all pregnant women (90%) were colonized by one or more multidrug-resistant (MDR) isolates with 58% being concomitantly ESBL producers. Altogether, 14 of 22 (64%) neonates were colonized by MDR isolates, while out of the 5 workers positive to Enterobacterales, all were colonized by MDR isolates. E coli predominated in pregnant women (55%) and neonates (73%), while K pneumoniae (83%) predominated in health care workers. The blaCTX-M (75%) was the leading ß-lactamase gene detected. CONCLUSIONS: Our study suggests that drug-resistant E coli and K pneumoniae are circulating at high prevalence in the labor ward in Yaoundé and emphasizes the necessity for effective infection prevention and control along with antimicrobial stewardship measures.
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Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. Streptococcus pneumoniae (the pneumococcus) is a respiratory bacterium responsible for a large proportion of infectious disease morbidity and mortality globally. Even in the post-vaccination era, the rates of invasive pneumococcal disease (IPD) remain stable in most countries, including Israel. To understand the geographical spread of the pneumococcus in Israel, we analysed 1174 pneumococcal genomes from patients with IPD across multiple regions. We included the evolutionary distance between pairs of isolates inferred using whole-genome data within a relative risk (RR) ratio framework to capture the geographical structure of S. pneumoniae. While we could not find geographical structure at the overall lineage level, the extra granularity provided by whole-genome sequence data showed that it takes approximately 5 years for invasive pneumococcal isolates to become fully mixed across the country.This article contains data hosted by Microreact.
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Genoma Bacteriano , Infecções Pneumocócicas , Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Israel/epidemiologia , Humanos , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/epidemiologia , Sequenciamento Completo do Genoma/métodos , Filogenia , GenômicaRESUMO
Streptococcus dysgalactiae subspecies equisimilis (SDSE) and Streptococcus pyogenes share skin and throat niches with extensive genomic homology and horizontal gene transfer (HGT) possibly underlying shared disease phenotypes. It is unknown if cross-species transmission interaction occurs. Here, we conduct a genomic analysis of a longitudinal household survey in remote Australian First Nations communities for patterns of cross-species transmission interaction and HGT. Collected from 4547 person-consultations, we analyse 294 SDSE and 315 S. pyogenes genomes. We find SDSE and S. pyogenes transmission intersects extensively among households and show that patterns of co-occurrence and transmission links are consistent with independent transmission without inter-species interference. We identify at least one of three near-identical cross-species mobile genetic elements (MGEs) carrying antimicrobial resistance or streptodornase virulence genes in 55 (19%) SDSE and 23 (7%) S. pyogenes isolates. These findings demonstrate co-circulation of both pathogens and HGT in communities with a high burden of streptococcal disease, supporting a need to integrate SDSE and S. pyogenes surveillance and control efforts.
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Transferência Genética Horizontal , Sequências Repetitivas Dispersas , Infecções Estreptocócicas , Streptococcus pyogenes , Streptococcus , Streptococcus pyogenes/genética , Streptococcus pyogenes/isolamento & purificação , Streptococcus pyogenes/classificação , Infecções Estreptocócicas/transmissão , Infecções Estreptocócicas/microbiologia , Humanos , Streptococcus/genética , Streptococcus/isolamento & purificação , Sequências Repetitivas Dispersas/genética , Austrália , Genoma Bacteriano/genética , Feminino , Masculino , Criança , Características da Família , Adulto , Pré-Escolar , Adolescente , Estudos Longitudinais , Farmacorresistência Bacteriana/genética , Adulto JovemRESUMO
The nasopharynx is an important reservoir of disease-associated and antimicrobial-resistant bacterial species. This proof-of-concept study assessed the utility of a combined culture, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and targeted metagenomic sequencing workflow for the study of the pediatric nasopharyngeal bacterial microbiota. Nasopharyngeal swabs and clinical metadata were collected from Cambodian children during a hospital outpatient visit and then biweekly for 12 weeks. Swabs were cultured on chocolate and blood-gentamicin agar, and all colony morphotypes were identified by MALDI-TOF MS. Metagenomic sequencing was done on a scrape of all colonies from a chocolate agar culture and processed using the mSWEEP pipeline. One hundred one children were enrolled, yielding 620 swabs. MALDI-TOF MS identified 106 bacterial species/40 genera: 20 species accounted for 88.5% (2,190/2,474) of isolates. Colonization by Moraxella catarrhalis (92.1% of children on ≥1 swab), Haemophilus influenzae (87.1%), and Streptococcus pneumoniae (83.2%) was particularly common. In S. pneumoniae-colonized children, a median of two serotypes [inter-quartile range (IQR) 1-2, range 1-4] was detected. For the 21 bacterial species included in the mSWEEP database and identifiable by MALDI-TOF, detection by culture + MALDI-TOF MS and culture + mSWEEP was highly concordant with a median species-level agreement of 96.9% (IQR 86.8%-98.8%). mSWEEP revealed highly dynamic lineage-level colonization patterns for S. pneumoniae which were quite different to those for S. aureus. A combined culture, MALDI-TOF MS, targeted metagenomic sequencing approach for the exploration of the young child nasopharyngeal microbiome was technically feasible, and each component yielded complementary data. IMPORTANCE: The human upper respiratory tract is an important source of disease-causing and antibiotic-resistant bacteria. However, understanding the interactions and stability of these bacterial populations is technically challenging. We used a combination of approaches to determine colonization patterns over a 3-month period in 101 Cambodian children. The combined approach was feasible to implement, and each component gave complementary data to enable a better understanding of the complex patterns of bacterial colonization.
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Bactérias , Metagenômica , Microbiota , Nasofaringe , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Nasofaringe/microbiologia , Microbiota/genética , Pré-Escolar , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Feminino , Metagenômica/métodos , Criança , Lactente , Masculino , Camboja , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/classificaçãoRESUMO
Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.
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Infecções Estreptocócicas , Streptococcus , Vacinas , Humanos , Streptococcus pyogenes/genética , Fluxo GênicoRESUMO
Streptococcus pneumoniae (the pneumococcus) is a globally distributed, human obligate opportunistic bacterial pathogen which, although often carried commensally, is also a significant cause of invasive disease. Apart from multi-drug resistant and virulent clones, the rate and direction of pneumococcal dissemination between different countries remains largely unknown. The ability for the pneumococcus to take a foothold in a country depends on existing population configuration, the extent of vaccine implementation, as well as human mobility since it is a human obligate bacterium. To shed light on its international movement, we used extensive genome data from the Global Pneumococcal Sequencing project and estimated migration parameters between multiple countries in Africa. Data on allele frequencies of polymorphisms at housekeeping-like loci for multiple different lineages circulating in the populations of South Africa, Malawi, Kenya, and The Gambia were used to calculate the fixation index (Fst) between countries. We then further used these summaries to fit migration coalescent models with the likelihood-free inference algorithms available in the ELFI software package. Synthetic datawere additionally used to validate the inference approach. Our results demonstrate country-pair specific migration patterns and heterogeneity in the extent of migration between different lineages. Our approach demonstrates that coalescent models can be effectively used for inferring migration rates for bacterial species and lineages provided sufficiently granular population genomics surveillance data. Further, it can demonstrate the connectivity of respiratory disease agents between countries to inform intervention policy in the longer term.
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Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Humanos , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/epidemiologia , Frequência do Gene , África , Quênia/epidemiologiaRESUMO
BACKGROUND: Streptococcus agalactiae, commonly known as Group B Streptococcus (GBS), exhibits a broad host range, manifesting as both a beneficial commensal and an opportunistic pathogen across various species. In humans, it poses significant risks, causing neonatal sepsis and meningitis, along with severe infections in adults. Additionally, it impacts livestock by inducing mastitis in bovines and contributing to epidemic mortality in fish populations. Despite its wide host spectrum, the mechanisms enabling GBS to adapt to specific hosts remain inadequately elucidated. Therefore, the development of a rapid and accurate method differentiates GBS strains associated with particular animal hosts based on genome-wide information holds immense potential. Such a tool would not only bolster the identification and containment efforts during GBS outbreaks but also deepen our comprehension of the bacteria's host adaptations spanning humans, livestock, and other natural animal reservoirs. METHODS AND RESULTS: Here, we developed three machine learning models-random forest (RF), logistic regression (LR), and support vector machine (SVM) based on genome-wide mutation data. These models enabled precise prediction of the host origin of GBS, accurately distinguishing between human, bovine, fish, and pig hosts. Moreover, we conducted an interpretable machine learning using SHapley Additive exPlanations (SHAP) and variant annotation to uncover the most influential genomic features and associated genes for each host. Additionally, by meticulously examining misclassified samples, we gained valuable insights into the dynamics of host transmission and the potential for zoonotic infections. CONCLUSIONS: Our study underscores the effectiveness of random forest (RF) and logistic regression (LR) models based on mutation data for accurately predicting GBS host origins. Additionally, we identify the key features associated with each GBS host, thereby enhancing our understanding of the bacteria's host-specific adaptations.
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Infecções Estreptocócicas , Streptococcus agalactiae , Feminino , Adulto , Animais , Humanos , Bovinos , Suínos , Streptococcus agalactiae/genética , Infecções Estreptocócicas/veterinária , Genômica , Peixes , Aprendizado de MáquinaRESUMO
Pakistan is amongst the four countries with the highest number of pneumococcal deaths. While the PCV10 vaccine was introduced in Pakistan in October 2012, data regarding the impact of the vaccine on the population dynamics of Streptococcus pneumoniae in Pakistan remain obscure. Using whole genome sequencing of 190 isolates (nasopharyngeal carriage=75, disease=113, unknown sites=2) collected between 2002 and 2020, this study presents characteristics of pneumococcal strains in Pakistan in the pre- and post-vaccine era. The isolates were characterized on the basis of serotype distribution, genetic lineages (or Global Pneumococcal Sequence Cluster, GPSC) and antibiotic resistance. A high level of diversity in serotype and genetic lineages of pneumococci was observed in Pakistan. Among 190 isolates, we identified 54 serotypes, 67 GPSCs and 116 sequence types (STs) including 23 new STs. The most prevalent GPSCs and their associated serotypes in nasopharyngeal carriage were GPSC54 (expressing serotype 9V), GPSC5 (15A and 7B, and serogroup 24), GPSC25 (15B/15C), GPSC67 (18C) and GPSC376 (6A and 6D). Similarly, among 113 disease-causing isolates, the most prevalent GPSC/serotype combinations were GPSC2 (serotype 1), GPSC10 (serotypes 14, 10A, 19A and 19F), GPSC43 (serotypes 13, 11A, 23B, 35A and 9V), GPSC67 (serotypes 18A and 18C) and GPSC642 (serotype 11A). Of the 190 isolates, the highest levels of resistance were observed against penicillin (58.9â%, n=122), erythromycin (29.5â%, n=56), clindamycin (13.2â%, n=25), co-trimoxazole (94.2â%, n=179) and tetracycline/doxycycline (53.2â%, n=101). A higher proportion of disease-causing isolates were multidrug resistant as compared to carriage isolates (54â% vs 25â%). Our data suggest limited coverage of PCV10 in nasopharyngeal (21.6â%, 16/74) as well as disease-causing (38.1â%, 16/42) isolates among children ≤5 years old; however, higher valent vaccine PCV13 would increase the coverage rates to 33.8 % in nasopharyngeal and 54.8â% in disease-causing isolates, whereas PCV24/25 would offer the highest coverage rates. Owing to the diversity of serotypes observed during the post-vaccine period, the suggested inclusion of serotype in future vaccine formulations will require investigations with larger data sets with an extended temporal window. This article contains data hosted by Microreact.
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Vacinas Pneumocócicas , Streptococcus pneumoniae , Criança , Humanos , Pré-Escolar , Paquistão/epidemiologia , Streptococcus pneumoniae/genética , Antibacterianos/farmacologiaRESUMO
Streptococcus pneumoniae (pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. This study characterises the immunoglobulin G (IgG) repertoire recognising pneumococci from birth to 24 months old (mo) in a prospectively-sampled cohort of 63 children using a panproteome array. IgG levels are highest at birth, due to transplacental transmission of maternal antibodies. The subsequent emergence of responses to individual antigens exhibit distinct kinetics across the cohort. Stable differences in the strength of individuals' responses, correlating with maternal IgG concentrations, are established by 6 mo. By 12 mo, children develop unique antibody profiles that are boosted by re-exposure. However, some proteins only stimulate substantial responses in adults. Integrating genomic data on nasopharyngeal colonisation demonstrates rare pneumococcal antigens can elicit strong IgG levels post-exposure. Quantifying such responses to the diverse core loci (DCL) proteins is complicated by cross-immunity between variants. In particular, the conserved N terminus of DCL protein zinc metalloprotease B provokes the strongest early IgG responses. DCL proteins' ability to inhibit mucosal immunity likely explains continued pneumococcal carriage despite hosts' polyvalent antibody repertoire. Yet higher IgG levels are associated with reduced incidence, and severity, of pneumonia, demonstrating the importance of the heterogeneity in response strength and kinetics across antigens and individuals.
Assuntos
Genômica , Streptococcus pneumoniae , Adulto , Recém-Nascido , Criança , Lactente , Humanos , Pré-Escolar , Streptococcus pneumoniae/genética , Imunoglobulina G , Imunidade nas Mucosas , Antígenos de BactériasRESUMO
IMPORTANCE: Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen with the greatest burden of disease in Asia and Africa. The pneumococcal capsular polysaccharide has biological relevance as a major virulence factor as well as public health importance as it is the target for currently licensed vaccines. These vaccines have limited valency, covering up to 23 of the >100 known capsular types (serotypes) with higher valency vaccines in development. Here, we have characterized a new pneumococcal serotype, which we have named 33G. We detected serotype 33G in nasopharyngeal swabs (n = 20) from children and adults hospitalized with pneumonia, as well as healthy children in Mongolia. We show that the genetic, serological, and biochemical properties of 33G differ from existing serotypes, satisfying the criteria to be designated as a new serotype. Future studies should focus on the geographical distribution of 33G and any changes in prevalence following vaccine introduction.
Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Humanos , Streptococcus pneumoniae/genética , Infecções Pneumocócicas/microbiologia , Sorogrupo , Vacinas Pneumocócicas , ÁsiaRESUMO
Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10â923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19â607, collected from 49 countries across 5 continents, 1995-2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2â%(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26â% (346/1353) and 53â% (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95â% CI) 0.24 (0.09-0.66); P=0.003], while GPSC46 was associated with disease [OR (95â% CI) 19.9 (2.56-906.50); P=0.0004]. Ten per cent (37/346) and 15â% (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18â% (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.