Markedly decreasing azithromycin susceptibility of Neisseria gonorrhoeae, Germany, 2014 to 2021

We monitored antimicrobial susceptibility developments of Neisseria gonorrhoeae in Germany from January 2014 to May 2021. The proportion of isolates with azithromycin minimum inhibitory concentrations above the epidemiological cut-off increased substantially, from 1.3% in 2014 to 12.2% in 2020. Preliminary data from 2021 showed a further rise (January to May: 20.7%). Therefore, azithromycin as part of the recommended dual therapy in Germany for non-adherent patients is challenged. Antimicrobial susceptibility testing in clinical practice is crucial and continuous susceptibility surveillance indispensable.Peer Reviewe

Epidemiologie und Resistenzlage der Gonorrhö in Deutschland im Jahr 2022

Das gramnegative Bakterium Neisseria gonorrhoeae (NG) ist der Erreger der Gonorrhö und wird durch direkten Schleimhautkontakt, z. B. beim Geschlechtsverkehr oder während der Geburt über-tragen. Infektionen mit NG können ein vielgestaltiges klinisches Bild zeigen und sind eine wesentliche Ursache von chronischen Entzündungen des kleinen Beckens, Unfruchtbarkeit, Fehlgeburten im ersten Trimenon und extrauterinen Schwangerschaften. Zusätzlich können Infektionen mit NG die Empfänglichkeit für HIV sowie das HIV-Übertragungsrisiko erhöhen. Innerhalb der letzten Jahrzehnte entwickelte NG zunehmend Resistenzen gegen alle wesentlichen Antibiotikaklassen, darunter Penicilline, Tetracycline, Makrolide sowie Fluorchinolone und seit einigen Jahren auch gegen Cephalosporine der dritten Generation. In der aktuell gültigen Leitlinie für Deutschland werden die Antibiotika Azithromycin, Cefixim und Ceftriaxon zur Behandlung der Gonorrhö empfohlen. Seit dem 1. März 2021 ist die nicht-namentliche Meldung von Infektionen mit NG mit verminderter Empfindlichkeit gegenüber mindestens einem dieser drei Antibiotika gemäß § 7 Abs. 3 des Infektionsschutzgesetztes verpflichtend. Der Beitrag gibt einen Überblick über die aktuelle Epidemiologie und Resistenzlage der Gonorrhö in Deutschland

Strategische Personalplanung und -entwicklung in der Berliner Verwaltung

STRATEGISCHE PERSONALPLANUNG UND -ENTWICKLUNG IN DER BERLINER VERWALTUNG Strategische Personalplanung und -entwicklung in der Berliner Verwaltung / Bluhm, Carola (Rights reserved) ( -

Targeting of a Chlamydial Protease Impedes Intracellular Bacterial Growth

Chlamydiae are obligate intracellular bacteria that propagate in a cytosolic vacuole. Recent work has shown that growth of Chlamydia induces the fragmentation of the Golgi apparatus (GA) into ministacks, which facilitates the acquisition of host lipids into the growing inclusion. GA fragmentation results from infection-associated cleavage of the integral GA protein, golgin-84. Golgin-84-cleavage, GA fragmentation and growth of Chlamydia trachomatis can be blocked by the peptide inhibitor WEHD-fmk. Here we identify the bacterial protease chlamydial protease-like activity factor (CPAF) as the factor mediating cleavage of golgin-84 and as the target of WEHD-fmk-inhibition. WEHD-fmk blocked cleavage of golgin-84 as well as cleavage of known CPAF targets during infection with C. trachomatis and C. pneumoniae. The same effect was seen when active CPAF was expressed in non-infected cells and in a cell-free system. Ectopic expression of active CPAF in non-infected cells was sufficient for GA fragmentation. GA fragmentation required the small GTPases Rab6 and Rab11 downstream of CPAF-activity. These results define CPAF as the first protein that is essential for replication of Chlamydia. We suggest that this role makes CPAF a potential anti-infective therapeutic target

Rab6 and Rab11 Regulate Chlamydia trachomatis Development and Golgin-84-Dependent Golgi Fragmentation

Many intracellular pathogens that replicate in special membrane bound compartments exploit cellular trafficking pathways by targeting small GTPases, including Rab proteins. Members of the Chlamydiaceae recruit a subset of Rab proteins to their inclusions, but the significance of these interactions is uncertain. Using RNA interference, we identified Rab6 and Rab11 as important regulators of Chlamydia infections. Depletion of either Rab6 or Rab11, but not the other Rab proteins tested, decreased the formation of infectious particles. We further examined the interplay between these Rab proteins and the Golgi matrix components golgin-84 and p115 with regard to Chlamydia-induced Golgi fragmentation. Silencing of the Rab proteins blocked Chlamydia-induced and golgin-84 knockdown-stimulated Golgi disruption, whereas Golgi fragmentation was unaffected in p115 depleted cells. Interestingly, p115-induced Golgi fragmentation could rescue Chlamydia propagation in Rab6 and Rab11 knockdown cells. Furthermore, transport of nutrients to Chlamydia, as monitored by BODIPY-Ceramide, was inhibited by Rab6 and Rab11 knockdown. Taken together, our results demonstrate that Rab6 and Rab11 are key regulators of Golgi stability and further support the notion that Chlamydia subverts Golgi structure to enhance its intracellular development

Drei Fälle von Gonorrhö mit ausgeprägter Antibiotika-Resistenz und Therapieversagen in Australien und Großbritannien

Im Februar 2018 wurde eine Infektion mit extensiv-resistenten Gonokokken (XDR-NG) in Großbritannien diagnostiziert, zwei weitere Fälle traten in Australien auf, wie WHO und ECDC berichten. Die Standardtherapeutika Ceftriaxon und Azithromycin waren in diesen Fällen mit Multiresistenz nicht mehr wirksam. Zudem waren die Isolate gegen die meisten anderen alternativ einsetzbaren Antibiotika (weitere Cephalosporine der 3. Generation, Chinolone, Tetracycline) ebenfalls resistent. Autoren aus dem RKI und dem Konsiliarlabor für Gonokokken erläutern im Epidemiologischen Bulletin 24/2018, worauf Ärzte und Labore in Deutschland achten sollten

CD46-Independent Binding of Neisserial Type IV Pili and the Major Pilus Adhesin, PilC, to Human Epithelial Cells

Neisseria gonorrhoeae is a gram-negative bacterial pathogen which infects the human mucosal epithelium. An early critical event in neisserial infection is the type IV pilus-mediated adherence to the host cell. The PilC protein, located on the pilus tip, has earlier been identified as the major pilus adhesin. Previous studies suggested that the cell surface protein CD46 is a pilus receptor for Neisseria. We investigated the role of CD46 in pilus-mediated gonococcal infection of epithelial cells. Differences in binding efficiencies of piliated gonococci as well as purified pilus adhesin PilC2 on human epithelial cell lines did not correlate to the level of surface-expressed CD46. Additionally, no binding of piliated gonococci or PilC2 protein was observed on CD46-transfected CHO and MDCK cells. Furthermore, specific down-regulation of CD46 expression in human epithelial cell lines by RNA interference did not alter the binding efficiency of piliated gonococci or purified PilC2 protein, although other CD46-dependent processes, such as measles virus infection and C3b cleavage, were significantly reduced. These data support the notion that pilus-mediated gonococcal infection of epithelial cells can occur in a CD46-independent manner, thus questioning the function of CD46 as an essential pilus receptor for pathogenic neisseriae

Is the hoopla over CPAF justified?

It may be worth asking whether all the hoopla over CPAF is justified. Our view is: yes, it is. As in any active scientific area, not every proposal regarding CPAF function has held up. The recent developments are very encouraging: we now have a much better idea of what CPAF can do, but also what it does not do. Our current knowledge can be summarized as follows: Chlamydiae produce a potent protease with unusual characteristics that is made by both pathogenic and environmental Chlamydiae, which likely transfers from the chlamydial inclusion into the cytosol, and which has the potential to cleave both bacterial and host proteins. We have recently and in more detailed fashion contributed to the discussion on CPAF in two commentaries (Conrad et al., 2013; Hacker, 2014) and will limit our comments here to several issues that have come up recently, which we think are important