Ph.D.
Nguyen Thi Khanh Nhu
Institute for Molecular Bioscience, The University of Queensland
Title: Roles of extracellular matrix in Uropathogenic Escherichia coli
Nhu Nguyen, Chitra Ravi, Steven J Hancock, Minh-Duy Phan, Mark A Schembri.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Uropathogenic Escherichia coli (UPEC) is the major cause of urinary tract infection (UTI). UPEC forms biofilms during UTI, leading to enhanced resistance to antibiotics and host immune factors. UPEC biofilm adhesins and production of an extracellular matrix comprising different combinations of curli amyloid fibres and the polysaccharide cellulose. These matrix components have different properties that influence infection outcomes, necessitating a need to understand their regulation and function.
In this study, we show that UPEC infection severity is associated with changes in the composition of the biofilm matrix, with UPEC strains that make curli (but not cellulose) causing augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of UTI. Using transposon-directed insertion site sequencing (TraDIS), we defined sets of genes required for curli and cellulose biosynthesis, including a new repressor gene referred to as rcpA that attenuates curli and cellulose biosynthesis when over-expressed. The rcpA gene encodes a small 93 amino acid protein predicted to localise to the inner membrane. Using RNAseq, we identified a signature of adaptation to stress and altered metabolism when RcpA over-expression. A second round of TraDIS was performed in an RcpA over-expression UPEC strain and showed its repression function is mediated via the CsgD master regulator that controls the transcription of curli and the c-di-GMP synthase DgcC required for cellulose production. We show this occurs via altered activity of the EnvZ sensor histidine kinase that works in partnership with the OmpR response regulator to control UPEC adaptation to stresses.
Overall, this study revealed diverse functions of UPEC biofilm matrix components during infection and identified a novel mechanism to switch off biofilm lifestyles.
Biography of the presenting author
Dr Nhu Nguyen completed her PhD in 2018 and is currently a Research Fellow at the Institute for Molecular Bioscience, The University of Queensland. She has expertise in molecular microbiology, bacterial genetics, genomics, and bioinformatics Her research focuses on the pathogenesis, antimicrobial resistance, and genomics of Escherichia coli responsible for extra-intestinal infections, including urinary tract infections, bloodstream infections, and neonatal meningitis.
Dr Nguyen has established a strong, rapidly emerging research profile, publishing 36 papers in high-impact journals including Nature Microbiology, Nature Communications, PNAS, and mBio. Her publications have attracted more than 3,500 citations, with an H-index of 27. She served as a member of the Early Career Editorial Board for mBio during 2024–2025 and is a frequent reviewer for several international journals.
Presenting author details
Full name: Dr. Nguyen Thi Khanh Nhu
Contact number:
Email: kn.nguyen@uq.edu.au
Google Scholar: http://scholar.google.com.au/citations?user=LZelUbcAAAAJ
ORCID: http://orcid.org/0000-0002-0158-850X
Website: http://about.uq.edu.au/experts/21831
Session name/ number: 4. Pathogenesis and infection
Category: Oral presentation