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Genomic epidemiology of clinical ESBL-producing Enterobacteriaceae in a German hospital suggests infections are primarily community- and regionally-acquired

Article

作者: Oravcova, Katarina ; Forde, Taya L. ; Köhler, Ute ; Tomasch, Jürgen ; Neffe, Lisa ; Bautsch, Wilfried ; Häussler, Susanne

Clinical

Enterobacteriaceae

isolates that produce extended-spectrum β-lactamases (ESBLs) have been increasingly reported at a global scale. However, comprehensive data on the molecular epidemiology of ESBL-producing strains are limited and few studies have been conducted in non-outbreak situations.We used whole-genome sequencing to describe the population structure of 294 ESBL-producing

Escherichia coli

and

Klebsiella pneumoniae

isolates that were recovered from a German community hospital throughout a 1 year sampling period in a non-outbreak situation.We found a high proportion of

E. coli

isolates (61.5 %) belonged to the globally disseminated extraintestinal pathogenic ST131, whereas a wider diversity of STs was observed among

K. pneumoniae

isolates. The

E. coli

ST131 population in this study was shaped by multiple introductions of strains as demonstrated by contextual genomic analysis including ST131 strains from other geographical sources. While no recent common ancestor of the isolates of the current study and other international isolates was found, our clinical isolates clustered with those previously recovered in the region. Furthermore, we found that the isolation of ESBL-producing clinical strains in hospitalized patients could only rarely be associated with likely patient-to-patient transmission, indicating primarily a community and regional acquisition of strains.Further genomic analyses of clinical, carriage and environmental isolates is needed to uncover hidden transmissions and thus discover the most common sources of ESBL-producing pathogen infections in our hospitals.

2021-08-01·EBioMedicine1区 · 医学

Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis

1区 · 医学

ArticleOA

作者: Kaiser, Philipp D ; Becker, Matthias ; Behrens, Georg M N ; Dulovic, Alex ; Ramos, Gema Morillas ; Lürken, Karsten ; Cossmann, Anne ; Beigel, Andrea ; Juengling, Jennifer ; Wrenger, Eike ; Dopfer-Jablonka, Alexandra ; Schneiderhan-Marra, Nicole ; Strengert, Monika ; Gruber, Jens ; Lonnemann, Gerhard ; Rothbauer, Ulrich ; Krause, Gérard ; Stankov, Metodi V ; Traenkle, Bjoern

BACKGROUNDPatients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population.METHODSWe assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay.FINDINGSPatients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished.INTERPRETATIONQuantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity.FUNDINGInitiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.

2021-01-01·Nature Immunology1区 · 医学

SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition

1区 · 医学

Article

作者: Peter, Andreas ; Kaiser, Philipp D ; Kowalewski, Daniel J ; Wacker, Marcel ; Walz, Juliane S ; Graf, Michael ; Märklin, Melanie ; Becker, Matthias ; Rabsteyn, Armin ; Preuß, Beate ; Schneiderhan-Marra, Nicole ; Lübke, Maren ; Salih, Helmut R ; Jäger, Elke ; Karbach, Julia ; Bauer, Jens ; Strengert, Monika ; Klein, Reinhild ; Kohlbacher, Oliver ; Maringer, Yacine ; Rachfalski, David ; Joos, Thomas O ; Fehr, Michael ; Rothbauer, Ulrich ; Rammensee, Hans-Georg ; Bilich, Tatjana ; Stevanović, Stefan ; Stos-Zweifel, Vlatka ; Rieth, Jonas ; Roerden, Malte ; Gruber, Lena-Christin ; Bakchoul, Tamam ; Hörber, Sebastian ; Junker, Daniel ; Mirakaj, Valbona ; Nelde, Annika ; Traenkle, Bjoern ; Krause, Gérard ; Templin, Markus F ; Gouttefangeas, Cécile ; Hagelstein, Ilona ; Heitmann, Jonas S

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.

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