Cargando…

Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis

Clonal bacterial cells can give rise to functionally heterogeneous subpopulations. This diversification is considered an adaptation strategy that has been demonstrated for several bacterial species, including Salmonella enterica serovar Typhimurium. In previous studies on mouse models infected orall...

Descripción completa

Detalles Bibliográficos
Autores principales: Gebremichael, Yismashoa, Crandall, John, Mukhopadhyay, Rituparna, Xu, Fengfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927314/
https://www.ncbi.nlm.nih.gov/pubmed/36507668
http://dx.doi.org/10.1128/spectrum.01679-22
_version_ 1784888455852982272
author Gebremichael, Yismashoa
Crandall, John
Mukhopadhyay, Rituparna
Xu, Fengfeng
author_facet Gebremichael, Yismashoa
Crandall, John
Mukhopadhyay, Rituparna
Xu, Fengfeng
author_sort Gebremichael, Yismashoa
collection PubMed
description Clonal bacterial cells can give rise to functionally heterogeneous subpopulations. This diversification is considered an adaptation strategy that has been demonstrated for several bacterial species, including Salmonella enterica serovar Typhimurium. In previous studies on mouse models infected orally with pure Salmonella cultures, derived bacterial cells collected from animal tissues were found to express heterogenous phenotypes. Here, we show mixed Salmonella populations, apparently derived from the same progenitor, present in human specimens collected at a single disease time point, and in a long-term-infected patient, these Salmonella were no longer expressing surface-exposed antigen epitopes by isolates collected at earlier days of the disease. The subpopulations express different phenotypes related to cell surface antigen expression, motility, biofilm formation, biochemical metabolism, and antibiotic resistance, which can all contribute to pathogenicity. Some of the phenotypes correlate with single nucleotide polymorphisms or other sequence changes in bacterial genomes. These genetic variations can alter synthesis of cell membrane-associated molecules such as lipopolysaccharides and lipoproteins, leading to changes in bacterial surface structure and function. This study demonstrates the limitation of Salmonella diagnostic methods that are based on a single-cell population which may not represent the heterogenous bacterial community in infected humans. IMPORTANCE In animal model systems, heterogenous Salmonella phenotypes were found previously to regulate bacterial infections. We describe in this communication that different Salmonella phenotypes also exist in infected humans at a single disease time point and that their phenotypic and molecular traits are associated with different aspects of pathogenicity. Notably, variation in genes encoding antibiotic resistance and two-component systems were observed from the subpopulations of a patient suffering from persistent salmonellosis. Therefore, clinical and public health interventions of the disease that are based on diagnosis of a single-cell population may miss other subpopulations that can cause residual human infections.
format Online
Article
Text
id pubmed-9927314
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-99273142023-02-15 Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis Gebremichael, Yismashoa Crandall, John Mukhopadhyay, Rituparna Xu, Fengfeng Microbiol Spectr Research Article Clonal bacterial cells can give rise to functionally heterogeneous subpopulations. This diversification is considered an adaptation strategy that has been demonstrated for several bacterial species, including Salmonella enterica serovar Typhimurium. In previous studies on mouse models infected orally with pure Salmonella cultures, derived bacterial cells collected from animal tissues were found to express heterogenous phenotypes. Here, we show mixed Salmonella populations, apparently derived from the same progenitor, present in human specimens collected at a single disease time point, and in a long-term-infected patient, these Salmonella were no longer expressing surface-exposed antigen epitopes by isolates collected at earlier days of the disease. The subpopulations express different phenotypes related to cell surface antigen expression, motility, biofilm formation, biochemical metabolism, and antibiotic resistance, which can all contribute to pathogenicity. Some of the phenotypes correlate with single nucleotide polymorphisms or other sequence changes in bacterial genomes. These genetic variations can alter synthesis of cell membrane-associated molecules such as lipopolysaccharides and lipoproteins, leading to changes in bacterial surface structure and function. This study demonstrates the limitation of Salmonella diagnostic methods that are based on a single-cell population which may not represent the heterogenous bacterial community in infected humans. IMPORTANCE In animal model systems, heterogenous Salmonella phenotypes were found previously to regulate bacterial infections. We describe in this communication that different Salmonella phenotypes also exist in infected humans at a single disease time point and that their phenotypic and molecular traits are associated with different aspects of pathogenicity. Notably, variation in genes encoding antibiotic resistance and two-component systems were observed from the subpopulations of a patient suffering from persistent salmonellosis. Therefore, clinical and public health interventions of the disease that are based on diagnosis of a single-cell population may miss other subpopulations that can cause residual human infections. American Society for Microbiology 2022-12-12 /pmc/articles/PMC9927314/ /pubmed/36507668 http://dx.doi.org/10.1128/spectrum.01679-22 Text en Copyright © 2022 Gebremichael et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Gebremichael, Yismashoa
Crandall, John
Mukhopadhyay, Rituparna
Xu, Fengfeng
Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis
title Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis
title_full Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis
title_fullStr Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis
title_full_unstemmed Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis
title_short Salmonella Subpopulations Identified from Human Specimens Express Heterogenous Phenotypes That Are Relevant to Clinical Diagnosis
title_sort salmonella subpopulations identified from human specimens express heterogenous phenotypes that are relevant to clinical diagnosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927314/
https://www.ncbi.nlm.nih.gov/pubmed/36507668
http://dx.doi.org/10.1128/spectrum.01679-22
work_keys_str_mv AT gebremichaelyismashoa salmonellasubpopulationsidentifiedfromhumanspecimensexpressheterogenousphenotypesthatarerelevanttoclinicaldiagnosis
AT crandalljohn salmonellasubpopulationsidentifiedfromhumanspecimensexpressheterogenousphenotypesthatarerelevanttoclinicaldiagnosis
AT mukhopadhyayrituparna salmonellasubpopulationsidentifiedfromhumanspecimensexpressheterogenousphenotypesthatarerelevanttoclinicaldiagnosis
AT xufengfeng salmonellasubpopulationsidentifiedfromhumanspecimensexpressheterogenousphenotypesthatarerelevanttoclinicaldiagnosis