Gastrointestinal infections

Clostridioides difficile

Clostridioides difficile is a spore-forming, anerobic, Gram-positive bacterium that colonizes the gastrointestinal tract of humans and animals. In humans, Clostridioides difficile is the primary cause of the clinical picture of antibiotic-associated colitis (pseudomembranous colitis). This life-threatening disease is one of the most common hospital-acquired infections in Germany, with several hundred to a thousand deaths per year.

Infection occurs through oral ingestion of spores that are characterized by high environmental resistance, especially to disinfectants. Patients whose intestinal microbiome has been damaged by previous treatment with antibiotics are particularly at risk. In this situation, known as dysbiosis, C. difficile finds ideal conditions to multiply in the intestine. An important pathogenicity factor is the production of toxins (toxin A and B, binary toxin), which damage the cells of the intestinal epithelium. Therapy is possible with selected antibiotics, such as metronidazole, vancomycin, or the newer fidaxomicin, which is more selective and less damaging to the endogenous gut microbiome.

Current research topics on C. difficile:

Flagella-based motility and chemotaxis of C. difficile.

Most C. difficile strains have flagella and are motile. To track and quantify the motility of single cells, we use video microscopy in combination with an in-house developed tracking program. Furthermore, we are investigating the components of the chemotaxis system and the factors that influence the chemotactic behavior of C. difficle.

Antibiotic resistance of C. difficile.

Commonly used antibiotics against C. difficile are vancomycin, metronidazole, and fidaxomicin. We are studying C. difficile strains of different origins for the presence of resistance to these antibiotics, exploring the mechanisms leading to antibiotic resistance and analyzing their impact on the general fitness of the bacterium.

Diversity of C. difficile strains

We characterize C. difficile isolates from different origins, e.g. isolates from different countries and regions, or isolates obtained from different age groups. In particular, we are interested in differences in pathogenic properties, such as toxin formation. Through this, we would like to be able to draw conclusions about the spreading behavior of individual C. difficile strains and explain different courses of disease.

Campylobacter jejuni and Campylobacter coli

Infections with the Gram-negative bacteria Campylobacter jejuni and Campylobacter coli are the main causes of bacterial diarrhea worldwide. Infection often occurs through consumption of contaminated food, such as poultry, as chickens are commonly colonized with Campylobacter species. Symptoms of C. jejuni infection can range from mild episodes of diarrhea, to bloody diarrhea with abdominal cramps. A feared late consequence of C. jejuni infection is Guillain-Barré syndrome, a serious neurologic disorder. Despite the high prevalence, the molecular mechanisms of the pathogenesis of campylobacteriosis, as well as the interaction of the pathogen with the gut microbiome, are poorly understood. 

Current research topics on Campylobacter:
Diversity of chemotactic behavior in different Campylobacter species and strains.

The chemotactic behavior of bacteria is critically determined by their repertoire of chemoreceptors. C. jejuni and C. coli are characterized by a large heterogeneity in the expression of chemoreceptors with different substrate specificities. We characterize the substrate specificities of chemoreceptors using molecular techniques and investigate the chemotactic behavior of Campylobacter strains. Our working hypothesis is that differences in chemotactic behavior are adaptations to different environmental conditions, such as preference for different hosts (humans, cattle, birds, etc.).   

Adaptation of C. jejuni to stress situations (e.g. bile salt stress).

The presence of bile salts represents a particular stress factor for intestinal bacteria due to their amphipathic character, to which they must be adapted. We investigate the change in the proteome caused by bile salts using mass spectrometric methods in order to understand adaptation mechanisms to this stress situation. 

Interaction of Campylobacter jejuni with the gut microbiome.

Campylobacter species must interact with the natural gut microbiome during the course of infection. We investigate a particular aspect of this microbial interaction by co-culturing C. jejuni with different representatives of Gram-positive intestinal bacteria. In the course of this cocultivation, changes in physiological properties occur, such as increased resistance to bile salts, the molecular causes of which we are investigating. 

Significance of the type 6 secretion system in C. jejuni.

Type-6 secretion systems enable bacteria to secrete effector proteins into target cells, such as other bacterial cells or eukaryotic cells, and thereby manipulate them in a targeted manner. The importance of the type-6 secretion system of C. jejuni is poorly understood and is being investigated by molecular techniques.

Publications on C. difficile

  1. Zimmermann O, Kochel H, Bohne W, Pollok-Kopp B, Passenberg P, Gross U. 2022. A Case Report and Review of the Literature: Reactive Arthritis Caused by Clostridioides difficile ribotype 027. Front Microbiol 13:837422.
  2. Schwanbeck J, Oehmig I, Gross U, Zautner AE, Bohne W. 2021. clostridioides difficile single cell swimming strategy: a novel motility pattern regulated by viscoelastic properties of the environment. Front Microbiol 12:715220.
  3. Tilkorn F, Frickmann H, Simon IS, Schwanbeck J, Horn S, Zimmermann O, Gross U, Bohne W, Zautner AE. 2020. antimicrobial resistance patterns in Clostridioides difficile strains isolated from neonates in Germany. Antibiotics (Basel) 9.
  4. Seugendo M, Hokororo A, Kabyemera R, Msanga DR, Mirambo MM, Silago V, Gross U, Mshana SE. 2020.High Clostridium difficile Infection among HIV-Infected Children with Diarrhea in a Tertiary Hospital in Mwanza, Tanzania. Int J Pediatr 2020:3264923.
  5. Riedel T, Neumann-Schaal M, Wittmann J, Schober I, Hofmann JD, Lu CW, Dannheim A, Zimmermann O, Lochner M, Gross U, Overmann J. 2020. characterization of Clostridioides difficile DSM 101085 with A-B-CDT+ phenotype from a Late Recurrent Colonization. Genome Biol Evol 12:566-577.
  6.  Frentrup M, Zhou Z, Steglich M, Meier-Kolthoff JP, Goker M, Riedel T, Bunk B, Sproer C, Overmann J, Blaschitz M, Indra A, von Muller L, Kohl TA, Niemann S, Seyboldt C, Klawonn F, Kumar N, Lawley TD, Garcia-Fernandez S, Canton R, Del Campo R, Zimmermann O, Gross U, Achtman M, Nubel U. 2020.A publicly accessible database for Clostridioides difficile genome sequences supports tracing of transmission chains and epidemics. Microb Genome 6.
  7.  Schwanbeck J, Riedel T, Laukien F, Schober I, Oehmig I, Zimmermann O, Overmann J, Gross U, Zautner AE, Bohne W. 2019. Characterization of a clinical Clostridioides difficile isolate with markedly reduced fidaxomicin susceptibility and a V1143D mutation in rpoB. J Antimicrob Chemother 74:6-10.
  8. Emele MF, Joppe FM, Riedel T, Overmann J, Rupnik M, Cooper P, Kusumawati RL, Berger FK, Laukien F, Zimmermann O, Bohne W, Gross U, Bader O, Zautner AE. 2019. proteotyping of Clostridioides difficile as Alternate Typing Method to Ribotyping Is Able to Distinguish the Ribotypes RT027 and RT176 From Other Ribotypes. Front Microbiol 10:2087.
  9. Seugendo M, Janssen I, Lang V, Hasibuan I, Bohne W, Cooper P, Daniel R, Gunka K, Kusumawati RL, Mshana SE, von Muller L, Okamo B, Ortlepp JR, Overmann J, Riedel T, Rupnik M, Zimmermann O, Gross U. 2018. Prevalence and Strain Characterization of Clostridioides (Clostridium) difficile in Representative Regions of Germany, Ghana, Tanzania and Indonesia - A Comparative Multi-Center Cross-Sectional Study. Front Microbiol 9:1843.
  10. Sachsenheimer FE, Yang I, Zimmermann O, Wrede C, Muller LV, Gunka K, Gross U, Suerbaum S. 2018. Genomic and phenotypic diversity of Clostridium difficile during long-term sequential recurrences of infection. Int J Med Microbiol 308:364-377.
  11. Gross U, Brzuszkiewicz E, Gunka K, Starke J, Riedel T, Bunk B, Sproer C, Wetzel D, Poehlein A, Chibani C, Bohne W, Overmann J, Zimmermann O, Daniel R, Liesegang H. 2018. Comparative genome and phenotypic analysis of three Clostridioides difficile strains isolated from a single patient provide insight into multiple infections of C. difficile. BMC Genomics 19:1.
  12. Schneider D, Thurmer A, Gollnow K, Lugert R, Gunka K, Gross U, Daniel R. 2017. Gut bacterial communities of diarrheic patients with indications of Clostridioides difficile infection. Sci Data 4:170152.
  13. Riedel T, Wetzel D, Hofmann JD, Plorin S, Dannheim H, Berges M, Zimmermann O, Bunk B, Schober I, Sproer C, Liesegang H, Jahn D, Overmann J, Gross U, Neumann-Schaal M. 2017. High metabolic versatility of different toxigenic and non-toxigenic Clostridioides difficile isolates. Int J Med Microbiol 307:311-320.
  14. Janssen I, Cooper P, Gunka K, Rupnik M, Wetzel D, Zimmermann O, Gross U. 2016. High prevalence of nontoxigenic Clostridium difficile isolated from hospitalized and non-hospitalized individuals in rural Ghana. Int J Med Microbiol 306:652-656.
  15. Seugendo M, Mshana SE, Hokororo A, Okamo B, Mirambo MM, von Muller L, Gunka K, Zimmermann O, Gross U. 2015. Clostridium difficile infections among adults and children in Mwanza/Tanzania: is it an underappreciated pathogen among immunocompromised patients in sub-Saharan Africa? New Microbes New Infect 8:99-102.

Campylobacter publications:

  1. Dieckmann AL, Riedel T, Bunk B, Sproer C, Overmann J, Gross U, Bader O, Bohne W, Morgenstern B, Hosseini M, Zautner AE. 2021. Genome and methylome analysis of a phylogenetically novel Campylobacter coli cluster with C. jejuni introgression. Microb Genome 7.
  2. Grade M, Gross U, Zautner AE. 2020. campylobacter enteritis. Journal of Gastroenterology 58:25-+.
  3. Masanta WO, Zautner AE, Lugert R, Bohne W, Gross U, Leha A, Dakna M, Lenz C. 2019. proteome profiling by label-free mass spectrometry reveals differentiated response of Campylobacter jejuni 81-176 to sublethal concentrations of bile acids. Proteomics Clinical Applications 13.
  4. Emele MF, Mozina SS, Lugert R, Bohne W, Masanta WO, Riedel T, Gross U, Bader O, Zautner AE. 2019. proteotyping as alternate typing method to differentiate Campylobacter coli clades. Scientific Reports 9.
  5. Lubke AL, Minatelli S, Riedel T, Lugert R, Schober I, Sproer C, Overmann J, Gross U, Zautner AE, Bohne W. 2018. The transducer-like protein Tlp12 of Campylobacter jejuni is involved in glutamate and pyruvate chemotaxis. Bmc Microbiology 18.
  6. Karg M, Frickmann H, Hotzel H, Lugert R, Gross U, Hagen RM, Tomaso H, Poppert S, Zautner AE. 2018. identification of Campylobacter fetus by fluorescence in situ hybridization (FISH). Journal of Microbiological Methods 151:44-47.
  7. Zautner AE, Lugert R, Masanta WO, Weig M, Gross U, Bader O. 2016. subtyping of Campylobacter jejuni ssp doylei isolates Using Mass Spectrometry-based PhyloProteomics (MSPP). Jove Journal of Visualized Experiments doi:ARTN e54165.
  8. Mund NL, Masanta WO, Goldschmidt AM, Lugert R, Gross U, Zautner AE. 2016. association of Campylobacter Jejuni ssp. Jejuni chemotaxis receptor genes with multilocus sequence types and source of isolation. Eur J Microbiol Immunol (Bp) 6:162-177.
  9. Lugert R, Gross U, Zautner AE. 2015. campylobacter jejuni: cornponents for adherence to and invasion of eukaryotic cells. Berliner Und Munchener Tierarztliche Wochenschrift 128:90-97.
  10.  Tareen AM, Luder CGK, Zautner AE, Gross U, Heimesaat MM, Bereswill S, Lugert R. 2013. The Campylobacter jejuni Cj0268c Protein Is Required for Adhesion and Invasion In Vitro. Plos One 8.
  11.  Zautner AE, Tareen AM, Gross U, Lugert R. 2012. chemotaxis in Campylobacter jejuni. Eur J Microbiol Immunol (Bp) 2:24-31.
  12.  Lugert R, Tareen AM, Dasti JI, Zautner AE, Gross U. 2011. characterization of new virulence factors of Campylobacter jejuni. International Journal of Medical Microbiology 301:61-61.
  13. Tareen AM, Dasti JI, Zautner AE, Gross U, Lugert R. 2010. Campylobacter jejuni proteins Cj0952c and Cj0951c affect chemotactic behaviour towards formic acid and are important for invasion of host cells. Microbiology 156:3123-3135.

 

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