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As other European countries, France is experiencing a resurgence of pertussis in 2024. Between 1 January and 31 May 2024, 5,616 (24.9%) positive Bordetella pertussis qPCR tests were identified, following a 3-year period of almost null incidence. Of 67 cultured and whole genome sequenced B. pertussis isolates, 66 produced pertactin and 56 produced FIM2, in contrast to pre-COVID-19 years. One isolate of genotype Bp-AgST4 was resistant to macrolides. Pertussis resurgence may favour isolates that produce FIM2 and pertactin.
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Antibacterianos , Bordetella pertussis , Macrólidos , Tos Ferina , Bordetella pertussis/genética , Bordetella pertussis/aislamiento & purificación , Bordetella pertussis/efectos de los fármacos , Humanos , Francia/epidemiología , Macrólidos/farmacología , Tos Ferina/epidemiología , Tos Ferina/microbiología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Proteínas de la Membrana Bacteriana Externa/genética , Secuenciación Completa del Genoma , Factores de Virulencia de Bordetella/genética , Genotipo , Adulto , Niño , Incidencia , PreescolarRESUMEN
Whole genome sequencing (WGS) has become a vital tool in clinical microbiology, playing an important role in outbreak investigations, molecular surveillance, and identification of bacterial species, resistance mechanisms and virulence factors. However, the complexity of WGS data presents challenges in interpretation and reporting, requiring tailored strategies to enhance efficiency and impact. This study explores the diverse needs of key stakeholders in healthcare, including clinical management, laboratory work, public surveillance and epidemiology, infection prevention and control, and academic research, regarding WGS-based reporting of clinically relevant bacterial species. In order to determine preferences regarding WGS reports, human-centered design approach was employed, involving an online survey and a subsequent workshop with stakeholders. The survey gathered responses from 64 participants representing the above mentioned healthcare sectors across geographical regions. Key findings include the identification of barriers related to data accessibility, integration with patient records, and the complexity of interpreting WGS results. As the participants designed their ideal report using nine pre-defined sections of a typical WGS report, differences in needs regarding report structure and content across stakeholders became evident. The workshop discussions further highlighted the need to feature critical findings and quality metrics prominently in reports, as well as the demand for flexible report designs. Commonalities were observed across stakeholder-specific reporting templates, such as the uniform ranking of certain report sections, but preferences regarding the depth of content within these sections varied. Using these findings, we suggest stakeholder-specific structures which should be considered when designing customized reporting templates. In conclusion, this study underscores the importance of tailoring WGS-based reports of clinically relevant bacteria to meet the distinct needs of diverse healthcare stakeholders. The evolving landscape of digital reporting increases the opportunities with respect to WGS reporting and its utility in managing infectious diseases and public health surveillance.
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Secuenciación Completa del Genoma , Humanos , Genoma Bacteriano/genética , Encuestas y CuestionariosRESUMEN
Between March and October 2022, a peak of detection of Bordetella parapertussis by qPCR, real-time PCR was observed in France.Hypothesis/Gap Statement. Whether this peak was due to resurgence from previous circulating lineages or reintroduction into the country was unknown.Objective. The objective of this study is to understand B. parapertussis-transient increase observed in France in 2022 whereas it had virtually stopped being reported since the start of the COVID-19 pandemic in 2020.Methods. We analysed real-time PCR (qPCR) data from the two largest French outpatient laboratories performing whooping cough diagnosis and characterized all B. parapertussis isolates collected in the 2016-2022 period by the French National Reference Centre for Whooping Cough.Results. Microbiological analyses reveal that 13 of 18 bacterial isolates collected in 2022 produce the vaccine antigen pertactin, whereas none of the 22 isolates collected in the 2016-2021 period did.Conclusion. We hypothesize a re-introduction of B. parapertussis from regions of the world where whole-cell vaccines are still in use.
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Bordetella parapertussis , Tos Ferina , Francia/epidemiología , Humanos , Bordetella parapertussis/genética , Bordetella parapertussis/aislamiento & purificación , Tos Ferina/epidemiología , Tos Ferina/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas de la Membrana Bacteriana Externa/genética , Infecciones por Bordetella/microbiología , Infecciones por Bordetella/epidemiología , Niño , Preescolar , Adulto , Factores de Virulencia de Bordetella/genética , Femenino , COVID-19/epidemiología , Adolescente , Lactante , Masculino , Adulto JovenRESUMEN
Human infections with Corynebacterium diphtheriae species complex (CdSC) bacteria were rare in French Guiana until 2016, when the number of cases diagnosed increased. We conducted an epidemiologic, multicenter, retrospective study of all human CdSC infections diagnosed in French Guiana during January 1, 2016-December 31, 2021. A total of 64 infectious episodes were observed in 60 patients; 61 infections were caused by C. diphtheriae and 3 by C. ulcerans. Estimated incidence increased from 0.7 cases/100,000 population in 2016 to 7.7 cases/100,000 population in 2021. The mean patient age was 30.4 (+23.7) years, and male-to-female ratio was 1.7:1 (38/22). Of the 61 C. diphtheriae isolates, 5 tested positive for the diphtheria toxin gene, and all results were negative by Elek test; 95% (61/64) of cases were cutaneous, including the C. ulcerans cases. The increase in reported human infections underscores the need to raise awareness among frontline healthcare practitioners to improve prevention.
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Corynebacterium diphtheriae , Difteria , Humanos , Guyana Francesa/epidemiología , Estudios Retrospectivos , Femenino , Masculino , Corynebacterium diphtheriae/aislamiento & purificación , Corynebacterium diphtheriae/genética , Adulto , Persona de Mediana Edad , Adolescente , Niño , Adulto Joven , Preescolar , Difteria/epidemiología , Difteria/microbiología , Anciano , Incidencia , Lactante , Historia del Siglo XXI , Infecciones por Corynebacterium/epidemiología , Infecciones por Corynebacterium/microbiologíaRESUMEN
We report a case of Klebsiella pneumoniae bacteraemia in an 80-year-old man in France with no history of travel to Asia, complicated by endogenous endophthalmitis, multiple cerebral microbleeds and hepatic microabscesses, associated with a Bentall endocarditis. Hypervirulence pathotype was suggested based on clinical picture, bacterial isolate genomic sequence and hypermucoidy. Interestingly, the isolate had the non-K1/K2-capsular serotype locus KL113-like, carried a KpVP-1-like virulence plasmid, and belonged to the emerging sublineage SL660 (comprising the sequence type ST660).
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Bacteriemia , Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/patogenicidad , Masculino , Anciano de 80 o más Años , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/diagnóstico , Bacteriemia/microbiología , Endoftalmitis/microbiología , Endoftalmitis/diagnóstico , Francia , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/diagnóstico , Hemorragia Cerebral/microbiologíaRESUMEN
CRISPR-Cas systems can be utilized as programmable-spectrum antimicrobials to combat bacterial infections. However, how CRISPR nucleases perform as antimicrobials across target sites and strains remains poorly explored. Here, we address this knowledge gap by systematically interrogating the use of CRISPR antimicrobials using multidrug-resistant and hypervirulent strains of Klebsiella pneumoniae as models. Comparing different Cas nucleases, DNA-targeting nucleases outperformed RNA-targeting nucleases based on the tested targets. Focusing on AsCas12a that exhibited robust targeting across different strains, we found that the elucidated modes of escape varied widely, restraining opportunities to enhance killing. We also encountered individual guide RNAs yielding different extents of clearance across strains, which were linked to an interplay between improper gRNA folding and strain-specific DNA repair and survival. To explore features that could improve targeting across strains, we performed a genome-wide screen in different K. pneumoniae strains that yielded guide design rules and trained an algorithm for predicting guide efficiency. Finally, we showed that Cas12a antimicrobials can be exploited to eliminate K. pneumoniae when encoded in phagemids delivered by T7-like phages. Altogether, our results highlight the importance of evaluating antimicrobial activity of CRISPR antimicrobials across relevant strains and define critical parameters for efficient CRISPR-based targeting.
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Sistemas CRISPR-Cas , Klebsiella pneumoniae , ARN Guía de Sistemas CRISPR-Cas , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , ARN Guía de Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/genética , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Asociadas a CRISPR/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Genoma Bacteriano/genética , Edición Génica/métodos , HumanosRESUMEN
Background: Microbial culture collections are valuable repositories for qualified and diverse microorganisms, playing a pivotal role in research, education, innovation, as well as in our response to current and emerging public health and societal challenges. However, such precious holdings, when not integrated in professional biobank infrastructures, may be vulnerable to major risks such as staff retirement, changes in the institutional strategy, or natural disasters. The process of preserving and rescuing "historical" collections can be long and treacherous with a loss of a part of the collection. At the Biological Resource Center of Institut Pasteur, we undertook the challenge of rescuing the dormant legacy fungal collection. Materials and Methods: A total of 64 freeze-dried strains, including yeasts and filamentous fungi, were characterized by using a polyphasic approach combining morphological features and molecular data. We assessed the viability, purity, and authenticity of selected strains isolated from multiple sources and stored for more than 20 years. Results: Our preliminary results show long-term stability of the selected strains and successful qualification in terms of purity and authentication. Moreover, based on the most recent taxonomic revisions, we updated and revised the nomenclature, where applicable. Conclusion: Our findings demonstrated the potential value of reviving historical microbial collections for biobanking and research activities and reassure us about the collection's future reopening.
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BACKGROUND: Evidence-based clinical susceptibility breakpoints have been lacking for antimicrobial agents used for diphtheria. OBJECTIVES: We aimed to evaluate broth microdilution and disc diffusion methods and create a dataset of MIC values and inhibition zone diameters (ZDs) from which breakpoints could be determined. METHODS: We included 400 recent clinical isolates equally distributed by species (Corynebacterium diphtheriae and Corynebacterium ulcerans) and by national surveillance programmes (France and Germany). Non-duplicate toxigenic and non-toxigenic isolates were chosen to enable the inclusion of a diversity of susceptibility levels for the 13 agents tested. Broth microdilution and disc diffusion, using EUCAST methodology for fastidious organisms, were used. RESULTS: The distributions of MIC and ZD values were largely in agreement among methods and countries. Breakpoints to allow categorization of WT isolates as susceptible, i.e. susceptible (S) or susceptible, increased exposure (I) were determined for 12 agents. The data supported a breakpoint for benzylpenicillin and amoxicillin of resistant (R)â>â1 mg/L since WT isolates were inhibited by 1 mg/L or less. WT isolates were categorized as I (Sâ≤â0.001 mg/L) for benzylpenicillin, emphasizing the need for increased exposure, and S (Sâ≤â1 mg/L) for amoxicillin. Erythromycin breakpoints were set at Sâ≤â0.06 mg/L and Râ>â0.06 mg/L. The corresponding ZD breakpoints were determined for all agents except amoxicillin, for which categorization was based on benzylpenicillin results. CONCLUSIONS: This work provided a large set of antimicrobial susceptibility data for C. diphtheriae and C. ulcerans, using a harmonized methodology. The dataset allowed EUCAST and experts in the diphtheria field to develop evidence-based breakpoints in January 2023.
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Antibacterianos , Corynebacterium diphtheriae , Corynebacterium , Pruebas de Sensibilidad Microbiana , Pruebas de Sensibilidad Microbiana/métodos , Humanos , Corynebacterium/efectos de los fármacos , Corynebacterium/aislamiento & purificación , Antibacterianos/farmacología , Corynebacterium diphtheriae/efectos de los fármacos , Corynebacterium diphtheriae/aislamiento & purificación , Corynebacterium diphtheriae/genética , Alemania , Infecciones por Corynebacterium/microbiología , Difteria/microbiología , FranciaRESUMEN
The Klebsiella pneumoniae species complex (KpSC) is a major source of nosocomial infections globally with high rates of resistance to antimicrobials. Consequently, there is growing interest in understanding virulence factors and their association with cellular metabolic processes for developing novel anti-KpSC therapeutics. Phenotypic assays have revealed metabolic diversity within the KpSC, but metabolism research has been neglected due to experiments being difficult and cost-intensive. Genome-scale metabolic models (GSMMs) represent a rapid and scalable in silico approach for exploring metabolic diversity, which compile genomic and biochemical data to reconstruct the metabolic network of an organism. Here we use a diverse collection of 507 KpSC isolates, including representatives of globally distributed clinically relevant lineages, to construct the most comprehensive KpSC pan-metabolic model to date, KpSC pan v2. Candidate metabolic reactions were identified using gene orthology to known metabolic genes, prior to manual curation via extensive literature and database searches. The final model comprised a total of 3550 reactions, 2403 genes and can simulate growth on 360 unique substrates. We used KpSC pan v2 as a reference to derive strain-specific GSMMs for all 507 KpSC isolates, and compared these to GSMMs generated using a prior KpSC pan-reference (KpSC pan v1) and two single-strain references. We show that KpSC pan v2 includes a greater proportion of accessory reactions (8.8â%) than KpSC pan v1 (2.5â%). GSMMs derived from KpSC pan v2 also generate more accurate growth predictions, with high median accuracies of 95.4â% (aerobic, n=37 isolates) and 78.8â% (anaerobic, n=36 isolates) for 124 matched carbon substrates. KpSC pan v2 is freely available at https://github.com/kelwyres/KpSC-pan-metabolic-model, representing a valuable resource for the scientific community, both as a source of curated metabolic information and as a reference to derive accurate strain-specific GSMMs. The latter can be used to investigate the relationship between KpSC metabolism and traits of interest, such as reservoirs, epidemiology, drug resistance or virulence, and ultimately to inform novel KpSC control strategies.
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Infección Hospitalaria , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Carbono , Bases de Datos Factuales , Genómica , KlebsiellaRESUMEN
Extensively drug-resistant (XDR) Klebsiella pneumoniae inflict a notable burden on healthcare worldwide. Of specific concern are strains producing carbapenem-hydrolyzing enzymes, as the therapeutic options for these strains are still very limited. Specific sequence types of K. pneumoniae have been noted for their epidemic occurrence globally, but the mechanisms behind the success of specific clones remain unclear. Herein, we have characterized 20 high-risk clones (HiRCs) and 10 non-HiRCs of XDR K. pneumoniae, exploring factors connected to the epidemiological success of some clones. Isolates were subjected to core genome multilocus sequence typing analysis to determine the clonal relationships of the isolates and subsequently characterized with regard to features known to be linked to overall bacterial fitness and virulence. The genomes were analyzed in silico for capsule types, O antigens, virulence factors, antimicrobial resistance genes, prophages, and CRISPR-Cas loci. In vitro growth experiments were conducted to retrieve proxies for absolute and relative fitness for 11 HiRC and 9 non-HiRC isolates selected based on the clonal groups they belonged to, and infections in a Galleria mellonella insect model were used to evaluate the virulence of the isolates in vivo. This study did not find evidence that virulence factors, prophages, CRISPR-Cas loci, or fitness measured in vitro alone would contribute to the global epidemiological success of specific clones of carbapenemase-producing XDR K. pneumoniae. However, this study did find the HiRC group to be more virulent than the non-HiRC group when measured in vivo in a model with G. mellonella. This suggests that the virulence and epidemiological success of certain clones of K. pneumoniae cannot be explained by individual traits investigated in this study and thus warrant further experiments in the future.IMPORTANCEHerein, we explored potential explanations for the successfulness of some epidemic or high-risk clones of carbapenemase-producing Klebsiella pneumoniae. We found differences in mortality in a larva model but found no clear genomic differences in known virulence markers. Most of the research on virulence in K. pneumoniae has been focused on hypervirulent strains, but here, we try to understand differences within the group of highly resistant strains. The results from the larva virulence model could be used to design experiments in higher animals. Moreover, the data could provide further support to a differentiated infection control approach against extensively drug-resistant strains, based on their classification as high-risk clones.
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Infecciones por Klebsiella , Klebsiella pneumoniae , Animales , Virulencia/genética , Klebsiella pneumoniae/genética , Infecciones por Klebsiella/microbiología , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Factores de Virulencia/genética , Larva , Células Clonales , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad MicrobianaRESUMEN
Introduction: Non-baumannii Acinetobacter species are increasingly isolated in the clinical setting and the environment. The aim of the present study was to analyze a genome database of 837 Acinetobacter spp. isolates, which included 798 non-baumannii Acinetobacter genomes, in order to define the concordance of classification and discriminatory power of 7-gene MLST, 53-gene MLST, and single-nucleotide polymorphism (SNPs) phylogenies. Methods: Phylogenies were performed on Pasteur Multilocus Sequence Typing (MLST) or ribosomal Multilocus Sequence Typing (rMLST) concatenated alleles, or SNPs extracted from core genome alignment. Results: The Pasteur MLST scheme was able to identify and genotype 72 species in the Acinetobacter genus, with classification results concordant with the ribosomal MLST scheme. The discriminatory power and genotyping reliability of the Pasteur MLST scheme were assessed in comparison to genome-wide SNP phylogeny on 535 non-baumannii Acinetobacter genomes assigned to Acinetobacter pittii, Acinetobacter nosocomialis, Acinetobacter seifertii, and Acinetobacter lactucae (heterotypic synonym of Acinetobacter dijkshoorniae), which were the most clinically relevant non-baumannii species of the A. baumannii group. The Pasteur MLST and SNP phylogenies were congruent at Robinson-Fould and Matching cluster tests and grouped genomes into four and three clusters in A. pittii, respectively, and one each in A. seifertii. Furthermore, A. lactucae genomes were grouped into one cluster within A. pittii genomes. The SNP phylogeny of A. nosocomialis genomes showed a heterogeneous population and did not correspond to the Pasteur MLST phylogeny, which identified two recombinant clusters. The antimicrobial resistance genes belonging to at least three different antimicrobial classes were identified in 91 isolates assigned to 17 distinct species in the Acinetobacter genus. Moreover, the presence of a class D oxacillinase, which is a naturally occurring enzyme in several Acinetobacter species, was found in 503 isolates assigned to 35 Acinetobacter species. Conclusion: In conclusion, Pasteur MLST phylogeny of non-baumannii Acinetobacter isolates coupled with in silico detection of antimicrobial resistance makes it important to study the population structure and epidemiology of Acinetobacter spp. isolates.
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We describe 10 unlinked cases of Corynebacterium diphtheriae infection (nine cutaneous, one respiratory) in France in 2023 in persons travelling from Guinea, Mali, Senegal, Niger or Nigeria and Central African Republic. Four isolates were toxigenic. Seven genomically unrelated isolates were multidrug-resistant, including a toxigenic respiratory isolate with high-level resistance to macrolides and beta-lactams. The high rates of resistance, including against first-line agents, call for further microbiological investigations to guide clinical management and public health response in ongoing West African outbreaks.
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Corynebacterium diphtheriae , Difteria , Humanos , Corynebacterium diphtheriae/genética , Difteria/diagnóstico , Difteria/tratamiento farmacológico , Difteria/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Francia/epidemiología , MalíRESUMEN
The Corynebacterium diphtheriae species complex comprises seven bacterial species, including Corynebacterium ulcerans, a zoonotic pathogen from multiple animal species. In this work, we characterise phenotypically and genotypically isolates belonging to two C. ulcerans lineages. Results from phylogenetic analyses, in silico DNA-DNA hybridization (DDH) and MALDI-TOF spectra differentiate lineage 2 from C. ulcerans lineage 1, which, together with their distinct transmission dynamics (probable human-to-human vs animal-to-human), indicates that lineage 2 is a separate Corynebacterium species, which we propose to name Corynebacterium ramonii. This species is of particular medical interest considering that its human-to-human transmission is likely, and that some C. ramonii isolates carry the diphtheria toxin gene.
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Clinical, epidemiologic, and microbiologic analyses revealed emergence of 26 cases of Corynebacterium diphtheriae species complex infections on Réunion Island, France, during 2015-2020. Isolates were genetically diverse, indicating circulation and local transmission of several diphtheria sublineages. Clinicians should remain aware of the risk for diphtheria and improve diagnostic methods and patient management.
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Infecciones por Corynebacterium , Corynebacterium diphtheriae , Difteria , Humanos , Difteria/microbiología , Toxina Diftérica , Infecciones por Corynebacterium/microbiología , Reunión/epidemiología , Corynebacterium , Francia/epidemiologíaRESUMEN
Increasing reports on K. pneumoniae strains with antimicrobial resistance and virulence traits from food and farm animals are raising concerns about the potential role of Klebsiella spp. as a foodborne pathogen. This study aimed to report and characterize Klebsiella spp. isolates from two artisanal ready-to-eat food (soft cheese and salami) producing facilities, and to track similar genotypes in different ecological niches. Over 1170 samples were collected during the whole production chain of different food batches. The overall Klebsiella prevalence was 6%. Strains were classified into the three Klebsiella species complexes: K. pneumoniae (KpSC, n = 17), K. oxytoca (KoSC, n = 38) and K. planticola (KplaSC, n = 18). Despite high genetic diversity we found in terms of known and new sequence types (STs), core genome phylogeny revealed clonal strains persisting in the same processing setting for over 14 months, isolated from the environment, raw materials and end-products. Strains showed a natural antimicrobial resistance phenotype-genotype. K. pneumoniae strains showed the highest virulence potential, with sequence types ST4242 and ST107 strains carrying yersiniabactin ybt16 and aerobactin iuc3. The latter was detected in all K. pneumoniae from salami and was located on a large conjugative plasmid highly similar (97% identity) to iuc3+ plasmids from human and pig strains circulating in nearby regions of Italy. While identical genotypes may persist along the whole food production process, different genotypes from distinct sources in the same facility shared an iuc3-plasmid. Surveillance in the food chain will be crucial to obtain a more comprehensive picture of the circulation of Klebsiella strains with pathogenic potential.
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Infecciones por Klebsiella , Klebsiella , Humanos , Animales , Porcinos , Klebsiella/genética , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae , Plásmidos , Genómica , Klebsiella oxytoca , Antibacterianos/farmacología , beta-Lactamasas/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-Kd phages). We show that anti-Kd phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-Kd phages induce a lower rate of resistance emergence in vitro and provide increased killing efficiency when in combination with anti-K phages. In vivo, anti-Kd phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development. IMPORTANCE Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-Kd phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants.
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Bacteriófagos , Infecciones por Klebsiella , Animales , Humanos , Ratones , Klebsiella pneumoniae/genética , Bacteriófagos/genética , Especificidad del Huésped , Antibacterianos/farmacología , Klebsiella , Infecciones por Klebsiella/terapia , Infecciones por Klebsiella/microbiologíaRESUMEN
INTRODUCTION: Bordetella pertussis still circulates worldwide despite vaccination. Fimbriae are components of some acellular pertussis vaccines. Population fluctuations of B. pertussis fimbrial serotypes (FIM2 and FIM3) are observed, and fim3 alleles (fim3-1 [clade 1] and fim3-2 [clade 2]) mark a major phylogenetic subdivision of B. pertussis. OBJECTIVES: To compare microbiological characteristics and expressed protein profiles between fimbrial serotypes FIM2 and FIM3 and genomic clades. METHODS: A total of 19 isolates were selected. Absolute protein abundance of the main virulence factors, autoagglutination and biofilm formation, bacterial survival in whole blood, induced blood cell cytokine secretion, and global proteome profiles were assessed. RESULTS: Compared to FIM3, FIM2 isolates produced more fimbriae, less cellular pertussis toxin subunit 1 and more biofilm, but auto-agglutinated less. FIM2 isolates had a lower survival rate in cord blood, but induced higher levels of IL-4, IL-8 and IL-1ß secretion. Global proteome comparisons uncovered 15 differentially produced proteins between FIM2 and FIM3 isolates, involved in adhesion and metabolism of metals. FIM3 isolates of clade 2 produced more FIM3 and more biofilm compared to clade 1. CONCLUSION: FIM serotype and fim3 clades are associated with proteomic and other biological differences, which may have implications on pathogenesis and epidemiological emergence.
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Bordetella pertussis , Tos Ferina , Humanos , Serogrupo , Proteínas Fimbrias/genética , Filogenia , Proteoma/genética , Proteómica , Factores de Virulencia de Bordetella/genética , Vacuna contra la Tos Ferina , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismoRESUMEN
Corynebacteria of the diphtheriae species complex (CdSC) can cause diphtheria in humans and have been reported from companion animals. We aimed to describe animal infection cases caused by CdSC isolates. A total of 18,308 animals (dogs, cats, horses, and small mammals) with rhinitis, dermatitis, nonhealing wounds, and otitis were sampled in metropolitan France (August 2019 to August 2021). Data on symptoms, age, breed, and the administrative region of origin were collected. Cultured bacteria were analyzed for tox gene presence, production of the diphtheria toxin, and antimicrobial susceptibility and were genotyped by multilocus sequence typing. Corynebacterium ulcerans was identified in 51 cases, 24 of which were toxigenic. Rhinitis was the most frequent presentation (18/51). Eleven cases (6 cats, 4 dogs, and 1 rat) were monoinfections. Large-breed dogs, especially German shepherds (9 of 28 dogs; P < 0.00001), were overrepresented. C. ulcerans isolates were susceptible to all tested antibiotics. tox-positive C. diphtheriae was identified in 2 horses. Last, 11 infections cases (9 dogs and 2 cats; mostly chronic otitis and 2 sores) had tox-negative C. rouxii, a recently defined species. C. rouxii and C. diphtheriae isolates were susceptible to most antibiotics tested, and almost all of these infections were polymicrobial. Monoinfections with C. ulcerans point toward a primary pathogenic potential to animals. C. ulcerans represents an important zoonotic risk, and C. rouxii may represent a novel zoonotic agent. This case series provides novel clinical and microbiological data on CdSC infections and underlines the need for management of animals and their human contacts. IMPORTANCE We report on the occurrence and clinical and microbiological characteristics of infections caused by members of the CdSC in companion animals. This is the first study based on the systematic analysis of a very large animal cohort (18,308 samples), which provides data on the frequency of CdSC isolates in various types of clinical samples from animals. Awareness of this zoonotic bacterial group remains low among veterinarians and veterinary laboratories, among which it is often considered commensal in animals. We suggest that in the case of CdSC detection in animals, the veterinary laboratories should be encouraged to send the samples to a reference laboratory for analysis of the presence of the tox gene. This work is relevant to the development of guidelines in the case of CdSC infections in animals and underlines their public health relevance given the zoonotic transmission risk.