ORCID Profile
0000-0002-4161-5007
Current Organisations
University of Basel
,
Monash University
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Publisher: Public Library of Science (PLoS)
Date: 07-04-2022
DOI: 10.1371/JOURNAL.PBIO.3001608
Abstract: Virulence gene expression can represent a substantial fitness cost to pathogenic bacteria. In the model entero-pathogen Salmonella Typhimurium ( S .Tm), such cost favors emergence of attenuated variants during infections that harbor mutations in transcriptional activators of virulence genes (e.g., hilD and hilC ). Therefore, understanding the cost of virulence and how it relates to virulence regulation could allow the identification and modulation of ecological factors to drive the evolution of S .Tm toward attenuation. In this study, investigations of membrane status and stress resistance demonstrate that the wild-type (WT) expression level of virulence factors embedded in the envelope increases membrane permeability and sensitizes S .Tm to membrane stress. This is independent from a previously described growth defect associated with virulence gene expression in S .Tm. Pretreating the bacteria with sublethal stress inhibited virulence expression and increased stress resistance. This trade-off between virulence and stress resistance could explain the repression of virulence expression in response to harsh environments in S .Tm. Moreover, we show that virulence-associated stress sensitivity is a burden during infection in mice, contributing to the inherent instability of S .Tm virulence. As most bacterial pathogens critically rely on deploying virulence factors in their membrane, our findings could have a broad impact toward the development of antivirulence strategies.
Publisher: Microbiology Society
Date: 10-2020
Abstract: During March 2017, a neonatal patient with severe diarrhoea subsequently developed septicaemia and died, with Klebsiella isolated as the causative microorganism. In keeping with infection control protocols, the coincident illness of an attending staff member and three other neonates with Klebsiella infection triggered an outbreak response, leading to microbiological assessment of isolates collected from the staff member and all 21 co-housed neonates. Multilocus sequence typing and genomic sequencing identified that the isolates from the 21 neonates were of a new Klebsiella sequence type, ST2727, and taxonomically belonged to K. quasipneumoniae subsp. similipneumoniae (formerly referred to as KpIIB). Genomic characterization showed that the isolated ST2727 strains had erged from other K. quasipneumoniae subsp. similipneumoniae strains at least 90 years ago, whereas the neonatal s les were highly similar with a genomic ergence of 3.6 months. There was no relationship to the Klebsiella isolate from the staff member. This demonstrates that no transmission occurred from staff to patient or between patients. Rather, the data suggest that ST2727 colonized each neonate from a common hospital source. Sequence-based analysis of the genomes revealed several genes for antimicrobial resistance and some virulence features, but suggest that ST2727 is neither extremely-drug resistant nor hypervirulent. Our results highlight the clinical significance and genomic properties of ST2727 and urge genome-based measures be implemented for diagnostics and surveillance within hospital environments. Additionally, the present study demonstrates the need to scale the power of genomic analysis in retrospective studies where relatively few s les are available.
Publisher: Cold Spring Harbor Laboratory
Date: 12-03-2020
DOI: 10.1101/2020.03.07.20032706
Abstract: During March of 2017 a neonate patient suffered severe diarrhea and subsequently developed septicemia and died, with Klebsiella isolated as the causative microorganism. Coincident illness of an attending staff member and three other neonates with Klebsiella triggered a response, leading to a detailed microbiological and genomics investigation of isolates collected from the staff member and all 21 co-housed neonates. Multilocus sequence typing and genomic sequencing identified that the Klebsiella from all 21 neonates was a new MLST ST2727, and belonged to a less frequently detected subspecies K. quasipneumoniae subsp. similipneumoniae (KpIIB). Genomic characterization showed that the isolated ST2727 strains had erged from other KpIIB strains at least years ago, whereas the neonate s les were highly similar with a genomic ergence of 3.6 months and not related to the staff member, indicating that transmission did not occur from staff to patient or between patient to patient, but were acquired from a common hospital source. The genomes revealed that the isolates contained the ubiquitous H gene responsible for resistance to penicillin G, cefoxitin and cephalosporin C, and all Kp-IIB strains were competent for host cell adhesion. Our results highlight the clinical significance and genomic properties of relatively mild, but persistent MLST types such as ST2727, and urges for genomic surveillance and eradication within hospital environments. Genome sequences generated in this study are available in NCBI under BioProject ID PRJNA610124. All bioinformatic protocols used to process the genomic data are available at jlab/KpIIB_ST2727 .
No related grants have been discovered for Andrea Rocker.