Genomic insights into the antimicrobial resistance and virulence of Helicobacter pylori isolates from gastritis patients in Pereira, Colombia.

BACKGROUND: Helicobacter pylori infects the stomach and/or small intestines in more than half of the human population. Infection with H. pylori is the most common cause of chronic gastritis, which can lead to more severe gastroduodenal pathologies such as peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. H. pylori infection is particularly concerning in Colombia in South America, where > 80% of the population is estimated to be infected with H. pylori and the rate of stomach cancer is one of the highest in the continent. RESULTS: We compared the antimicrobial susceptibility profiles and short-read genome sequences of five H. pylori isolates obtained from patients diagnosed with gastritis of varying severity (chronic gastritis, antral erosive gastritis, superficial gastritis) in Pereira, Colombia sampled in 2015. Antimicrobial susceptibility tests revealed the isolates to be resistant to at least one of the five antimicrobials tested: four isolates were resistant to metronidazole, two to clarithromycin, two to levofloxacin, and one to rifampin. All isolates were susceptible to tetracycline and amoxicillin. Comparative genome analyses revealed the presence of genes associated with efflux pump, restriction modification systems, phages and insertion sequences, and virulence genes including the cytotoxin genes cagA and vacA. The five genomes represent three novel sequence types. In the context of the Colombian and global populations, the five H. pylori isolates from Pereira were phylogenetically distant to each other but were closely related to other lineages circulating in the country. CONCLUSIONS: H. pylori from gastritis of different severity varied in their antimicrobial susceptibility profiles and genome content. This knowledge will be useful in implementing appropriate eradication treatment regimens for specific types of gastritis. Understanding the genetic and phenotypic heterogeneity in H. pylori across the geographical landscape is critical in informing health policies for effective disease prevention and management that is most effective at local and country-wide scales. This is especially important in Colombia and other South American countries that are poorly represented in global genomic surveillance studies of bacterial pathogens.

Establishing a national reference laboratory for antimicrobial resistance using a whole-genome sequencing framework: Nigeria's experience.

Whole-genome sequencing (WGS) is finding important applications in the surveillance of antimicrobial resistance (AMR), providing the most granular data and broadening the scope of niches and locations that can be surveilled. A common but often overlooked application of WGS is to replace or augment reference laboratory services for AMR surveillance. WGS has supplanted traditional strain subtyping in many comprehensive reference laboratories and is now the gold standard for rapidly ruling isolates into or out of suspected outbreak clusters. These and other properties give WGS the potential to serve in AMR reference functioning where a reference laboratory did not hitherto exist. In this perspective, we describe how we have employed a WGS approach, and an academic-public health system collaboration, to provide AMR reference laboratory services in Nigeria, as a model for leapfrogging to national AMR surveillance.

Evolutionary dynamics of the accessory genomes of Staphylococcus aureus.

Staphylococcus aureus is a ubiquitous commensal and opportunistic bacterial pathogen that can cause a wide gamut of infections, which are exacerbated by the presence of multidrug-resistant and methicillin-resistant S. aureus. S. aureus is genetically heterogeneous and consists of numerous distinct lineages. Using 558 complete genomes of S. aureus, we aim to determine how the accessory genome content among phylogenetic lineages of S. aureus is structured and has evolved. Bayesian hierarchical clustering identified 10 sequence clusters, of which seven contained major sequence types (ST 1, 5, 8, 30, 59, 239, and 398). The seven sequence clusters differed in their accessory gene content, including genes associated with antimicrobial resistance and virulence. Focusing on the two largest clusters, BAPS8 and BAPS10, and each consisting mostly of ST5 and ST8, respectively, we found that the structure and connected components in the co-occurrence networks of accessory genomes varied between them. These differences are explained, in part, by the variation in the rates at which the two sequence clusters gained and lost accessory genes, with the highest rate of gene accumulation occurring recently in their evolutionary histories. We also identified a divergent group within BAPS10 that has experienced high gene gain and loss early in its history. Together, our results show highly variable and dynamic accessory genomes in S. aureus that are structured by the history of the specific lineages that carry them.IMPORTANCEStaphylococcus aureus is an opportunistic, multi-host pathogen that can cause a variety of benign and life-threatening infections. Our results revealed considerable differences in the structure and evolution of the accessory genomes of major lineages within S. aureus. Such genomic variation within a species can have important implications on disease epidemiology, pathogenesis of infection, and interactions with the vertebrate host. Our findings provide important insights into the underlying genetic basis for the success of S. aureus as a highly adaptable and resistant pathogen, which will inform current efforts to control and treat staphylococcal diseases.

Assessing the risk of exposure to antimicrobial resistance at public beaches: Genome-based insights into the resistomes, mobilomes and virulomes of beta-lactams resistant Enterobacteriaceae from recreational beaches in Lagos, Nigeria.

The role of recreational water use in the acquisition and transmission of antimicrobial resistance (AMR) is under-explored in low- and middle-income countries (LMICs). We used whole genome sequence analysis to provide insights into the resistomes, mobilomes and virulomes of 14 beta-lactams resistant Enterobacterales isolated from water and wet-sand at four recreational beaches in Lagos, Nigeria. Carriage of multiple beta-lactamase genes was detected in all isolates except two, including six isolates carrying blaNDM-1. Most detected antibiotic resistance genes (ARGs) were located within a diverse landscape of plasmids, insertion sequences and transposons including the presence of ISKpn14 upstream of blaNDM-1 in a first report in Africa. Virulence genes involved in adhesion and motility as well as secretion systems are particularly abundant in the genomes of the isolates. Our results confirmed the four beaches are contaminated with bacteria carrying clinically relevant ARGs associated with mobile genetic elements (MGE) which could promote the transmission of ARGs at the recreational water-human interface.

Clonal background and routes of plasmid transmission underlie antimicrobial resistance features of bloodstream Klebsiella pneumoniae.

Bloodstream infections caused by the opportunistic pathogen Klebsiella pneumoniae are associated with adverse health complications and high mortality rates. Antimicrobial resistance (AMR) limits available treatment options, thus exacerbating its public health and clinical burden. Here, we aim to elucidate the population structure of K. pneumoniae in bloodstream infections from a single medical center and the drivers that facilitate the dissemination of AMR. Analysis of 136 short-read genome sequences complemented with 12 long-read sequences shows the population consisting of 94 sequence types (STs) and 99 clonal groups, including globally distributed multidrug resistant and hypervirulent clones. In vitro antimicrobial susceptibility testing and in silico identification of AMR determinants reveal high concordance (90.44-100%) for aminoglycosides, beta-lactams, carbapenems, cephalosporins, quinolones, and sulfonamides. IncF plasmids mediate the clonal (within the same lineage) and horizontal (between lineages) transmission of the extended-spectrum beta-lactamase gene blaCTX-M-15. Nearly identical plasmids are recovered from isolates over a span of two years indicating long-term persistence. The genetic determinants for hypervirulence are carried on plasmids exhibiting genomic rearrangement, loss, and/or truncation. Our findings highlight the importance of considering both the genetic background of host strains and the routes of plasmid transmission in understanding the spread of AMR in bloodstream infections.

Long-term persistence of diverse clones shapes the transmission landscape of invasive Listeria monocytogenes.

BACKGROUND: The foodborne bacterium Listeria monocytogenes (Lm) causes a range of diseases, from mild gastroenteritis to invasive infections that have high fatality rate in vulnerable individuals. Understanding the population genomic structure of invasive Lm is critical to informing public health interventions and infection control policies that will be most effective especially in local and regional communities. METHODS: We sequenced the whole draft genomes of 936 Lm isolates from human clinical samples obtained in a two-decade active surveillance program across 58 counties in New York State, USA. Samples came mostly from blood and cerebrospinal fluid. We characterized the phylogenetic relationships, population structure, antimicrobial resistance genes, virulence genes, and mobile genetic elements. RESULTS: The population is genetically heterogenous, consisting of lineages I-IV, 89 clonal complexes, 200 sequence types, and six known serogroups. In addition to intrinsic antimicrobial resistance genes (fosX, lin, norB, and sul), other resistance genes tetM, tetS, ermG, msrD, and mefA were sparsely distributed in the population. Within each lineage, we identified clusters of isolates with ≤ 20 single nucleotide polymorphisms in the core genome alignment. These clusters may represent isolates that share a most recent common ancestor, e.g., they are derived from the same contamination source or demonstrate evidence of transmission or outbreak. We identified 38 epidemiologically linked clusters of isolates, confirming eight previously reported disease outbreaks and the discovery of cryptic outbreaks and undetected chains of transmission, even in the rarely reported Lm lineage III (ST3171). The presence of animal-associated lineages III and IV may suggest a possible spillover of animal-restricted strains to humans. Many transmissible clones persisted over several years and traversed distant sites across the state. CONCLUSIONS: Our findings revealed the bacterial determinants of invasive listeriosis, driven mainly by the diversity of locally circulating lineages, intrinsic and mobile antimicrobial resistance and virulence genes, and persistence across geographical and temporal scales. Our findings will inform public health efforts to reduce the burden of invasive listeriosis, including the design of food safety measures, source traceback, and outbreak detection.

Genotypic Characterisation and Antimicrobial Resistance of Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Humans, Animals, and the Environment from Lusaka, Zambia: Public Health Implications and One Health Surveillance.

BACKGROUND: Extended-spectrum ß-lactamases (ESBL) in Escherichia coli are a serious concern due to their role in developing multidrug resistance (MDR) and difficult-to-treat infections. OBJECTIVE: This study aimed to identify ESBL-carrying E. coli strains from both clinical and environmental sources in Lusaka District, Zambia. METHODS: This cross-sectional study included 58 ESBL-producing E. coli strains from hospital inpatients, outpatients, and non-hospital environments. Antimicrobial susceptibility was assessed using the Kirby-Bauer disk diffusion method and the VITEK® 2 Compact System, while genotypic analyses utilised the Illumina NextSeq 2000 sequencing platform. RESULTS: Among the strains isolated strains, phylogroup B2 was the most common, with resistant MLST sequence types including ST131, ST167, ST156, and ST69. ESBL genes such as blaTEM-1B, blaCTX-M,blaOXA-1, blaNDM-5, and blaCMY were identified, with ST131 and ST410 being the most common. ST131 exhibited a high prevalence of blaCTX-M-15 and resistance to fluoroquinolones. Clinical and environmental isolates carried blaNDM-5 (3.4%), with clinical isolates showing a higher risk of carbapenemase resistance genes and the frequent occurrence of blaCTX-M and blaTEM variants, especially blaCTX-M-15 in ST131. CONCLUSIONS: This study underscores the public health risks of blaCTX-M-15- and blaNDM-5-carrying E. coli. The strengthening antimicrobial stewardship programmes and the continuous surveillance of AMR in clinical and environmental settings are recommended to mitigate the spread of resistant pathogens.

Ecology shapes the genomic and biosynthetic diversification of Streptomyces bacteria from insectivorous bats.

Streptomyces are prolific producers of secondary metabolites from which many clinically useful compounds have been derived. They inhabit diverse habitats but have rarely been reported in vertebrates. Here, we aim to determine to what extent the ecological source (bat host species and cave sites) influence the genomic and biosynthetic diversity of Streptomyces bacteria. We analysed draft genomes of 132 Streptomyces isolates sampled from 11 species of insectivorous bats from six cave sites in Arizona and New Mexico, USA. We delineated 55 species based on the genome-wide average nucleotide identity and core genome phylogenetic tree. Streptomyces isolates that colonize the same bat species or inhabit the same site exhibit greater overall genomic similarity than they do with Streptomyces from other bat species or sites. However, when considering biosynthetic gene clusters (BGCs) alone, BGC distribution is not structured by the ecological or geographical source of the Streptomyces that carry them. Each genome carried between 19-65 BGCs (median=42.5) and varied even among members of the same Streptomyces species. Nine major classes of BGCs were detected in ten of the 11 bat species and in all sites: terpene, non-ribosomal peptide synthetase, polyketide synthase, siderophore, RiPP-like, butyrolactone, lanthipeptide, ectoine, melanin. Finally, Streptomyces genomes carry multiple hybrid BGCs consisting of signature domains from two to seven distinct BGC classes. Taken together, our results bring critical insights to understanding Streptomyces-bat ecology and BGC diversity that may contribute to bat health and in augmenting current efforts in natural product discovery, especially from underexplored or overlooked environments.

Five centuries of genome evolution and multi-host adaptation of Campylobacter jejuni in Brazil.

Consumption of raw, undercooked or contaminated animal food products is a frequent cause of Campylobacter jejuni infection. Brazil is the world's third largest producer and a major exporter of chicken meat, yet population-level genomic investigations of C. jejuni in the country remain scarce. Analysis of 221 C. jejuni genomes from Brazil shows that the overall core and accessory genomic features of C. jejuni are influenced by the identity of the human or animal source. Of the 60 sequence types detected, ST353 is the most prevalent and consists of samples from chicken and human sources. Notably, we identified the presence of diverse bla genes from the OXA-61 and OXA-184 families that confer beta-lactam resistance as well as the operon cmeABCR related to multidrug efflux pump, which contributes to resistance against tetracyclines, macrolides and quinolones. Based on limited data, we estimated the most recent common ancestor of ST353 to the late 1500s, coinciding with the time the Portuguese first arrived in Brazil and introduced domesticated chickens into the country. We identified at least two instances of ancestral chicken-to-human infections in ST353. The evolution of C. jejuni in Brazil was driven by the confluence of clinically relevant genetic elements, multi-host adaptation and clonal population growth that coincided with major socio-economic changes in poultry farming.

Predictive identification and design of potent inhibitors targeting resistance-inducing candidate genes from E. coli whole-genome sequences.

Introduction: This work utilizes predictive modeling in drug discovery to unravel potential candidate genes from Escherichia coli that are implicated in antimicrobial resistance; we subsequently target the gidB, MacB, and KatG genes with some compounds from plants with reported antibacterial potentials. Method: The resistance genes and plasmids were identified from 10 whole-genome sequence datasets of E. coli; forty two plant compounds were selected, and their 3D structures were retrieved and optimized for docking. The 3D crystal structures of KatG, MacB, and gidB were retrieved and prepared for molecular docking, molecular dynamics simulations, and ADMET profiling. Result: Hesperidin showed the least binding energy (kcal/mol) against KatG (-9.3), MacB (-10.7), and gidB (-6.7); additionally, good pharmacokinetic profiles and structure-dynamics integrity with their respective protein complexes were observed. Conclusion: Although these findings suggest hesperidin as a potential inhibitor against MacB, gidB, and KatG in E. coli, further validations through in vitro and in vivo experiments are needed. This research is expected to provide an alternative avenue for addressing existing antimicrobial resistances associated with E. coli's MacB, gidB, and KatG.

Diversity, functional classification and genotyping of SHV ß-lactamases in Klebsiella pneumoniae.

Interpreting the phenotypes of bla SHV alleles in Klebsiella pneumoniae genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal bla SHV alleles or additional plasmid-borne bla SHV alleles that have extended-spectrum ß-lactamase (ESBL) activity and/or ß-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood. This has led to confusion in the literature and in antimicrobial resistance (AMR) gene databases [e.g. the National Center for Biotechnology Information (NCBI) Reference Gene Catalog and the ß-lactamase database (BLDB)] over the specific functionality of individual sulfhydryl variable (SHV) protein variants. Therefore, the identification of ESBL-producing strains from K. pneumoniae genome data is complicated. Here, we reviewed the experimental evidence for the expansion of SHV enzyme function associated with specific aa substitutions. We then systematically assigned SHV alleles to functional classes (WT, ESBL and BLI resistant) based on the presence of these mutations. This resulted in the re-classification of 37 SHV alleles compared with the current assignments in the NCBI's Reference Gene Catalog and/or BLDB (21 to WT, 12 to ESBL and 4 to BLI resistant). Phylogenetic and comparative genomic analyses support that (i) SHV-1 (encoded by bla SHV-1) is the ancestral chromosomal variant, (ii) ESBL- and BLI-resistant variants have evolved multiple times through parallel substitution mutations, (iii) ESBL variants are mostly mobilized to plasmids and (iv) BLI-resistant variants mostly result from mutations in chromosomal bla SHV. We used matched genome-phenotype data from the KlebNET-GSP AMR Genotype-Phenotype Group to identify 3999 K. pneumoniae isolates carrying one or more bla SHV alleles but no other acquired ß-lactamases to assess genotype-phenotype relationships for bla SHV. This collection includes human, animal and environmental isolates collected between 2001 and 2021 from 24 countries. Our analysis supports that mutations at Ambler sites 238 and 179 confer ESBL activity, whilst most omega-loop substitutions do not. Our data also provide support for the WT assignment of 67 protein variants, including 8 that were noted in public databases as ESBL. These eight variants were reclassified as WT because they lack ESBL-associated mutations, and our phenotype data support susceptibility to third-generation cephalosporins (SHV-27, SHV-38, SHV-40, SHV-41, SHV-42, SHV-65, SHV-164 and SHV-187). The approach and results outlined here have been implemented in Kleborate v2.4.1 (a software tool for genotyping K. pneumoniae), whereby known and novel bla SHV alleles are classified based on causative mutations. Kleborate v2.4.1 was updated to include ten novel protein variants from the KlebNET-GSP dataset and all alleles in public databases as of November 2023. This study demonstrates the power of sharing AMR phenotypes alongside genome data to improve the understanding of resistance mechanisms.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.

A snapshot survey of antimicrobial resistance in food-animals in low and middle-income countries.

Antimicrobial resistance remains a threat to global public health. Low-and middle-income countries carry a greater burden of resistance because of higher rates of infection as well as, potentially, location-specific risk factors. Food animals occupy a critical crossover point for the spread of antimicrobial resistance to humans and the environment. However, this domain remains poorly surveilled outside high-income settings. We used point surveillance from 191 studies reporting phenotypic AMR in food animals across 38 African, Middle Eastern, Asian and South and Central American countries to depict antimicrobial resistance trend in food animals. By computing Multiple Antibiotic Resistance indices and finding an overall mean of 0.34 ± 0.16, which is above the 0.2 index associated with multidrug resistance and high risk, we show that multidrug resistance in bacteria from food animal sources is worryingly high. MAR indexes from food animals were overall higher than those previously computed from aquaculture but, unlike aquaculture-computed MAR indices, did not track closely with those of human-associated bacteria in the same countries. Food animals are an important reservoir for rising antimicrobial resistance in bacteria, and hence improved surveillance in this sector is highly recommended.

Phylogenetic lineages and antimicrobial resistance determinants of clinical Klebsiella oxytoca spanning local to global scales.

Klebsiella oxytoca is an opportunistic pathogen causing serious nosocomial infections. Knowledge about the population structure and diversity of healthcare-associated K. oxytoca from a genomic standpoint remains limited. Here, we characterized the phylogenetic relationships and genomic characteristics of 20 K. oxytoca sensu stricto isolates recovered from bloodstream infections at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA from 2017 to 2021. Results revealed a diverse population consisting of 15 sequence types (STs) that together harbored 10 variants of the intrinsic beta-lactamase gene bla OXY-2, conferring resistance to penicillins. Similar sets of antimicrobial resistance (AMR) determinants reside in multiple distinct lineages, with no one lineage dominating the local population. To place the New Hampshire K. oxytoca in a broader context, we compared them to 304 publicly available genomes of clinical isolates from 18 countries. This global clinical K. oxytoca sensu stricto population is represented by over 65 STs that together harbored resistance genes against 14 antimicrobial classes, including eight bla OXY-2 variants. Three dominant STs in the global population (ST2, ST176, ST199) circulate across multiple countries and were also present in the New Hampshire population. The global K. oxytoca population is genetically diverse, but there is evidence for broad dissemination of a few lineages carrying distinct set of AMR determinants. Our findings reveal the clinical diversity of K. oxytoca sensu stricto and its importance in surveillance efforts aimed at monitoring the evolution of this drug-resistant nosocomial pathogen. IMPORTANCE The opportunistic pathogen Klebsiella oxytoca has been increasingly implicated in patient morbidity and mortality worldwide, including several outbreaks in healthcare settings. The emergence and spread of antimicrobial resistant strains exacerbate the disease burden caused by this species. Our study showed that clinical K. oxytoca sensu stricto is phylogenetically diverse, harboring various antimicrobial resistance determinants and bla OXY-2 variants. Understanding the genomic and population structure of K. oxytoca is important for international initiatives and local epidemiological efforts for surveillance and control of drug-resistant K. oxytoca.

Proteus mirabilis isolated from untreated hospital wastewater, Ibadan, Southwestern Nigeria showed low-level resistance to fluoroquinolone and carried qnrD3 on Col3M plasmids.

Untreated wastewater emanating from healthcare facilities are risk factors for the spread of antimicrobial resistance (AMR) at the human-environment interface. In this study, we investigated the determinants of resistance in three multidrug resistant strains of Proteus mirabilis isolated from untreated wastewater collected from three government owned hospitals in Ibadan, Nigeria. Despite showing low-level resistance to ciprofloxacin, whole genome sequencing revealed the transferable mechanism of quinolone resistance (TMQR) gene qnrD3 carried on Col3M plasmids in all the isolates. Core genome phylogenetic analysis showed the isolates are closely related differing from each other by ≤ 23 single nucleotide polymorphisms (SNP). Further, they shared the closest evolutionary relationship with isolates from China. Similarly, the Col3M plasmids is most closely related to p3M-2A found in P. vulgaris 3 M isolated from the intestine of shrimps in China. This to the best of our knowledge is the first report of Col3M plasmids carrying qnrD3 in environmental bacterial isolates. Our results indicate a possible silent spread of this important plasmid associated with the dissemination of qnrD3 in Nigeria, and further highlights the important role played by untreated wastewater from healthcare facilities in the spread of AMR in low- and middle-income countries.

Leaky barriers to gene sharing between locally co-existing coagulase-negative Staphylococcus species.

Coagulase-negative Staphylococcus (CoNS) are opportunistic pathogens implicated in many human and animal infections. The evolutionary history of CoNS remains obscure because of the historical lack of recognition for their clinical importance and poor taxonomic sampling. Here, we sequenced the genomes of 191 CoNS isolates representing 15 species sampled from diseased animals diagnosed in a veterinary diagnostic laboratory. We found that CoNS are important reservoirs of diverse phages, plasmids and mobilizable genes encoding antimicrobial resistance, heavy metal resistance, and virulence. Frequent exchange of DNA between certain donor-recipient partners suggests that specific lineages act as hubs of gene sharing. We also detected frequent recombination between CoNS regardless of their animal host species, indicating that ecological barriers to horizontal gene transfer can be surmounted in co-circulating lineages. Our findings reveal frequent but structured patterns of transfer that exist within and between CoNS species, which are driven by their overlapping ecology and geographical proximity.

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium's analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps.

A bottom-up view of antimicrobial resistance transmission in developing countries.

Antimicrobial resistance (AMR) is tracked most closely in clinical settings and high-income countries. However, resistant organisms thrive globally and are transmitted to and from healthy humans, animals and the environment, particularly in many low- and middle-income settings. The overall public health and clinical significance of these transmission opportunities remain to be completely clarified. There is thus considerable global interest in promoting a One Health view of AMR to enable a more realistic understanding of its ecology. In reality, AMR surveillance outside hospitals remains insufficient and it has been very challenging to convincingly document transmission at the interfaces between clinical specimens and other niches. In this Review, we describe AMR and its transmission in low- and middle-income-country settings, emphasizing high-risk transmission points such as urban settings and food-animal handling. In urban and food production settings, top-down and infrastructure-dependent interventions against AMR that require strong regulatory oversight are less likely to curtail transmission when used alone and should be combined with bottom-up AMR-containment approaches. We observe that the power of genomics to expose transmission channels and hotspots is largely unharnessed, and that existing and upcoming technological innovations need to be exploited towards containing AMR in low- and middle-income settings.

Draft Genome Sequences of Multidrug-Resistant Shiga Toxin-Producing Escherichia coli O116:H25 Strains from Ready-to-Eat Foods Sold in Lagos, Nigeria.

Draft genomes of multidrug-resistant Shiga toxin-producing Escherichia coli (STEC) strains IPK9(1) and IKS1(2), which were isolated from ready-to-eat foods (kokoro and shawarma) sold in Lagos, Nigeria, are reported. The genomes possessed genetic determinants for virulence and the antibiotic resistance gene for macrolide-associated resistance mdf(A). Ready-to-eat foods increase public health threats in Nigeria.

Genome Sequencing of Methicillin-Resistant and Methicillin-Susceptible Mammaliicoccus sciuri from Diseased Animals.

Mammaliicoccus sciuri (previously Staphylococcus sciuri) is a frequent colonizer of mammals. We report the draft genomes of a methicillin-resistant strain (2254A) isolated from an armadillo and a methicillin-susceptible strain (6942A) from a cow. Genomes were sequenced using long-read Nanopore sequencing.