Helen Wang research group

Plasmid Dynamics in Bacterial Pathogens

Plasmids in Enterobacteriaceae often encode virulence determinants and multi-antibiotic resistance that contribute to bacterial fitness during infection and antimicrobial treatments. Our prior research established that up-regulation of the plasmid copy number is an essential virulence mechanism in human pathogen Yersinia pseudotuberculosis. This newly-discovered regulatory strategy is most likely widespread amongst plasmid-carrying bacteria, enabling rapid adjustments of plasmid-encoded functions in response to environmental cues. Using genetic and biochemical tools, as well as both in vitro and in vivo models, we are identifying and dissecting key components involved in controlling plasmid copy number.

Plasmid Copy Number in Antibiotic Resistance

We recently demonstrated that increased gene dosage via plasmid copy number elevation is a prevalent and widespread mechanism for generating transient antibiotic resistance. Notably, the high instability and fitness costs associated with increased plasmid copy number lead to a rapid reversion to antibiotic susceptibility in the absence of antibiotics. This phenomenon is often overlooked in clinical settings, and likely contributes to failures in antibiotic treatments. By employing a systems biology approach that integrates in vitro, in vivo and clinical data from various clinically relevant bacterial species, we aim to gain a comprehensive understanding of the complex interplay between host bacteria, plasmids and resistance genes.

Polymicrobial Biofilms on UTI Catheters

Our research focuses on the virulence mechanisms of bacterial pathogens that pose significant challenges in clinical settings. One aspect of our work tracks infection patterns and investigates how antibiotic treatment impacts the bladder microbiome, often promoting resistant bacteria or contributing to recurrent urinary tract infections (UTI). We study the heterogeneity within bacterial populations, exploring genetic and phenotypic differences that affect their pathogenic potential, including the role of plasmids carrying antibiotic resistance genes or virulence factors. Grounded in clinical data, our primary focus is biofilm formation on urinary catheters, a critical issue in hospitals due to biofilms’ resistance to antibiotics and host immune responses. A key area of our research is polymicrobial biofilms, particularly those involving Enterococcus and E. coli, which are frequently found together in UTI. By investigating their interactions, we aim to uncover novel strategies for disrupting or preventing these biofilms, ultimately improving patient outcomes.

We are grateful to the Swedish Society for Medical Research (SSMF), the Swedish Research Council (VR), the Carl Tryggers Foundation, the Petrus och Augusta Hedlunds foundation, the Clas Groschinskys Foudation, the Ollie och Elof Ericssons Foundation, and others, for their generous support of our research.