: Typhimurium ST313 exhibits signatures of adaptation to invasive human infection, including higher resistance to humoral immune responses than gastrointestinal isolates. Full resistance to antibody-mediated complement killing (serum resistance) among nontyphoidal is uncommon, but selection of highly resistant strains could compromise vaccine-induced antibody immunity. Here, we address the hypothesis that serum resistance is due to a distinct genotype or transcriptome response in . Typhimurium ST313. : Six . Typhimurium ST313 bloodstream isolates, three of which were antibody resistant, were studied. Genomic content (single nucleotide polymorphisms and larger chromosomal modifications) of the strains was determined by Illumina and PACBIO sequencing, and functionally characterized using RNA-seq, transposon directed insertion site sequencing (TraDIS), targeted gene deletion and transfer of selected point mutations in an attempt to identify features associated with serum resistance. : Sequence polymorphisms in genes from strains with atypical serum susceptibility when transferred from strains that were highly resistant or susceptible to a strain that exhibited intermediate susceptibility did not significantly alter serum killing phenotype. No large chromosomal modifications typified serum resistance or susceptibility. Genes required for resistance to serum identified by TraDIS and RNA-seq included those involved in exopolysaccharide synthesis, iron scavenging and metabolism. Most of the down-regulated genes were associated with membrane proteins. Resistant and susceptible strains had distinct transcriptional responses to serum, particularly related to genes responsible for polysaccharide biosynthesis. There was higher upregulation of locus genes, involved in the biosynthesis of colanic acid exopolysaccharide, in susceptible strains and increased expression of , a regulator of very long-chain lipopolysaccharide in resistant strains. : Clinical isolates of . Typhimurium ST313 exhibit distinct antibody susceptibility phenotypes that may be associated with changes in gene expression on exposure to serum.
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http://dx.doi.org/10.12688/wellcomeopenres.15059.1 | DOI Listing |
Microbiol Spectr
June 2024
Department of Food Science & Technology, School of Agriculture and Biology, State Key Lab of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai, China.
Unlabelled: serovar Typhimurium is an important foodborne pathogen associated with human salmonellosis worldwide. A retrospective screening was performed to elucidate the prevalence, antimicrobial resistance, and phylogenomic characterization of this pathogen in Shanghai, China. .
View Article and Find Full Text PDFGut Microbes
May 2024
Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA.
The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant .
View Article and Find Full Text PDFMicrolife
March 2024
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.
Invasive non-typhoidal (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa. serovar Typhimurium ST313 causes the majority of iNTS in Malawi. We performed an intensive comparative genomic analysis of 608 .
View Article and Find Full Text PDFBMJ Open
January 2024
Department of Infectious Disease, Imperial College London, London, UK
Introduction: Invasive non-typhoidal (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%-20%. Several iNTS vaccine candidates are in early-stage assessment which-if found effective-would provide a valuable public health tool to reduce iNTS disease burden.
View Article and Find Full Text PDFFront Microbiol
November 2023
Department of Microbiology, National Institute for Biomedical Research, Kinshasa, Democratic Republic of Congo.
Invasive non-typhoidal (iNTS) (serotypes Typhimurium and Enteritidis) are major causes of bloodstream infections in sub-Saharan Africa, but their reservoir is unknown. Aiming to demonstrate human carriers as a reservoir, we assessed an iNTS disease endemic rural community (Kikonka health area, Democratic Republic of the Congo) for intestinal carriage of iNTS. After a census, healthy subjects from randomly selected households provided three successive stool samples for culture.
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