Dr Katrin Schilcher

Bacterial Interactions & Regulatory Networks

Research Highlights

Bacterial lipoproteins; Linear peptides; Signalling-Crosstalk and Interference; Polymicrobial Infections; Horizontal Gene transfer; Antibiotic Resistance

Research Summary

Society faces a significant challenge as the emergence and spread of multidrug-resistant bacteria continues to threaten our ability to treat bacterial infections. Lipoproteins of the opportunistic pathogen Staphylococcus aureus play a crucial role in various cellular processes and host interactions. We have identified several secreted linear peptides derived from the secretion signal sequences of staphylococcal lipoproteins and demonstrated that S. aureus lipoproteins not only consist of two functional components - a lipid moiety and a protein moiety - but also a small, secreted linear peptide. We provided the first evidence of distinct biological functions for the protein moiety and its associated linear peptide of a specific lipoprotein. While the protein component of the S. aureus lipoprotein CamS acts as an important repressor of toxins, the corresponding linear peptide can promote interspecies horizontal gene transfer (HGT), possibly contributing to the transmission of antimicrobial resistance (AMR) within a bacterial community.

In my research lab, we aim to understand how bacterial regulatory networks control lipoproteins and their corresponding peptides and affect bacterial physiology and cell-cell signalling. Exploring S. aureus linear peptide-mediated responses is intriguing due to their potential for cross-talk and interference within the species and other co-infecting pathogens. Bacterial interactions in polymicrobial infections can profoundly affect infecting microbes and lead to alterations in gene expression, virulence factor production, bacterial metabolism and antibiotic resistance. We seek to decipher changes in the gene transcription profile of S. aureus during interactions with co-infecting microbes, elucidate determinants that drive bacterial competition and co-existence in polymicrobial infections and analyse how bacterial interactions influences staphylococcal virulence and AMR. With this approach we will determine how co-infecting bacteria from polymicrobial infections influence bacterial infection dynamics and antibiotic resistance at the molecular level.

selected Publications:

Schilcher K*, Severn MM, Jenul C, Avina YC, Keogh RA, Horswill AR*. 2024. The Staphylococcus aureus CamS lipoprotein is a repressor of toxin production that shapes host-pathogen interaction. PLoS Biol 22:e3002451. doi: 10.1371/journal.pbio.3002451. *co-corresponding authors

Jenul C, Keim KC, Jens JN, Zeiler MJ, Schilcher K, Schurr MJ, Melander C, Phelan VV, Horswill AR. 2023. Pyochelin biotransformation by Staphylococcus aureus shapes bacterial competition with Pseudomonas aeruginosa in polymicrobial infections. Cell Rep 42:112540. doi: 10.1016/j.celrep.2023.112540.

Schilcher K, Horswill AR. 2020. Staphylococcal Biofilm Development: Structure, Regulation, and Treatment Strategies. Microbiol Mol Biol Rev 84: :e00026-19. doi: 10.1128/MMBR.00026-19.

Schilcher K*, Caesar LK, Cech NB, Horswill AR*. 2020. Processing, Export, and Identification of Novel Linear Peptides from Staphylococcus aureus. mBio 11:e00112-20. doi: 10.1128/mBio.00112-20. *co-corresponding authors

Schilcher K*, Andreoni F, Dengler Haunreiter V, Seidl K, Hasse B, Zinkernagel AS*. 2016. Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin. Antimicrob Agents Chemother 60:5957-67. doi: 10.1128/AAC.00463-16. *co-corresponding authors

Schilcher K, Andreoni F, Uchiyama S, Ogawa T, Schuepbach RA, Zinkernagel AS. 2014. Increased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin. J Infect Dis 210:473-82. doi: 10.1093/infdis/jiu091.