Editorial

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Open AccessEditorial

Special Issue “Salmonella: Pathogenesis and Host Restriction”

by France Daigle

Microorganisms 2021, 9(2), 325; https://doi.org/10.3390/microorganisms9020325 - 05 Feb 2021

Cited by 1 | Viewed by 1855

Bacteria of the Salmonella genus include several serovars that are closely related, although they can colonize different ecological niches, different hosts, and cause different diseases [...] Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

Research

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18 pages, 2124 KiB

Open AccessArticle

The Salmonella enterica Plasmidome as a Reservoir of Antibiotic Resistance

by Jean-Guillaume Emond-Rheault, Jérémie Hamel, Julie Jeukens, Luca Freschi, Irena Kukavica-Ibrulj, Brian Boyle, Sandeep Tamber, Danielle Malo, Eelco Franz, Elton Burnett, France Daigle, Gitanjali Arya, Kenneth Sanderson, Martin Wiedmann, Robin M. Slawson, Joel T. Weadge, Roger Stephan, Sadjia Bekal, Samantha Gruenheid, Lawrence D. Goodridge and Roger C. Levesque Show full author list Hide full author list

Microorganisms 2020, 8(7), 1016; https://doi.org/10.3390/microorganisms8071016 - 08 Jul 2020

Cited by 19 | Viewed by 5061

Abstract

The emergence of multidrug-resistant bacterial strains worldwide has become a serious problem for public health over recent decades. The increase in antimicrobial resistance has been expanding via plasmids as mobile genetic elements encoding antimicrobial resistance (AMR) genes that are transferred vertically and horizontally. [...] Read more.

The emergence of multidrug-resistant bacterial strains worldwide has become a serious problem for public health over recent decades. The increase in antimicrobial resistance has been expanding via plasmids as mobile genetic elements encoding antimicrobial resistance (AMR) genes that are transferred vertically and horizontally. This study focuses on Salmonella enterica, one of the leading foodborne pathogens in industrialized countries. S. enterica is known to carry several plasmids involved not only in virulence but also in AMR. In the current paper, we present an integrated strategy to detect plasmid scaffolds in whole genome sequencing (WGS) assemblies. We developed a two-step procedure to predict plasmids based on i) the presence of essential elements for plasmid replication and mobility, as well as ii) sequence similarity to a reference plasmid. Next, to confirm the accuracy of the prediction in 1750 S. enterica short-read sequencing data, we combined Oxford Nanopore MinION long-read sequencing with Illumina MiSeq short-read sequencing in hybrid assemblies for 84 isolates to evaluate the proportion of plasmid that has been detected. At least one scaffold with an origin of replication (ORI) was predicted in 61.3% of the Salmonella isolates tested. The results indicated that IncFII and IncI1 ORIs were distributed in many S. enterica serotypes and were the most prevalent AMR genes carrier, whereas IncHI2A/IncHI2 and IncA/C2 were more serotype restricted but bore several AMR genes. Comparison between hybrid and short-read assemblies revealed that 81.1% of plasmids were found in the short-read sequencing using our pipeline. Through this process, we established that plasmids are prevalent in S. enterica and we also substantially expand the AMR genes in the resistome of this species. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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25 pages, 4640 KiB

Open AccessArticle

Metabolic Activation of CsgD in the Regulation of Salmonella Biofilms

by Akosiererem S. Sokaribo, Elizabeth G. Hansen, Madeline McCarthy, Taseen S. Desin, Landon L. Waldner, Keith D. MacKenzie, George Mutwiri, Jr., Nancy J. Herman, Dakoda J. Herman, Yejun Wang and Aaron P. White

Microorganisms 2020, 8(7), 964; https://doi.org/10.3390/microorganisms8070964 - 27 Jun 2020

Cited by 15 | Viewed by 4049

Abstract

Among human food-borne pathogens, gastroenteritis-causing Salmonella strains have the most real-world impact. Like all pathogens, their success relies on efficient transmission. Biofilm formation, a specialized physiology characterized by multicellular aggregation and persistence, is proposed to play an important role in the Salmonella transmission [...] Read more.

Among human food-borne pathogens, gastroenteritis-causing Salmonella strains have the most real-world impact. Like all pathogens, their success relies on efficient transmission. Biofilm formation, a specialized physiology characterized by multicellular aggregation and persistence, is proposed to play an important role in the Salmonella transmission cycle. In this manuscript, we used luciferase reporters to examine the expression of csgD, which encodes the master biofilm regulator. We observed that the CsgD-regulated biofilm system responds differently to regulatory inputs once it is activated. Notably, the CsgD system became unresponsive to repression by Cpx and H-NS in high osmolarity conditions and less responsive to the addition of amino acids. Temperature-mediated regulation of csgD on agar was altered by intracellular levels of RpoS and cyclic-di-GMP. In contrast, the addition of glucose repressed CsgD biofilms seemingly independent of other signals. Understanding the fine-tuned regulation of csgD can help us to piece together how regulation occurs in natural environments, knowing that all Salmonella strains face strong selection pressures both within and outside their hosts. Ultimately, we can use this information to better control Salmonella and develop strategies to break the transmission cycle. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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17 pages, 2916 KiB

Open AccessArticle

New Roles for Two-Component System Response Regulators of Salmonella enterica Serovar Typhi during Host Cell Interactions

by Claudie Murret-Labarthe, Maud Kerhoas, Karine Dufresne and France Daigle

Microorganisms 2020, 8(5), 722; https://doi.org/10.3390/microorganisms8050722 - 13 May 2020

Cited by 17 | Viewed by 3839

Abstract

In order to survive external stresses, bacteria need to adapt quickly to changes in their environment. One adaptive mechanism is to coordinate and alter their gene expression by using two-component systems (TCS). TCS are composed of a sensor kinase that activates a transcriptional [...] Read more.

In order to survive external stresses, bacteria need to adapt quickly to changes in their environment. One adaptive mechanism is to coordinate and alter their gene expression by using two-component systems (TCS). TCS are composed of a sensor kinase that activates a transcriptional response regulator by phosphorylation. TCS are involved in motility, virulence, nutrient acquisition, and envelope stress in many bacteria. The pathogenic bacteria Salmonella enterica serovar Typhi (S. Typhi) possess 30 TCSs, is specific to humans, and causes typhoid fever. Here, we have individually deleted each of the 30 response regulators. We have determined their role during interaction with host cells (epithelial cells and macrophages). Deletion of most of the systems (24 out of 30) resulted in a significant change during infection. We have identified 32 new phenotypes associated with TCS of S. Typhi. Some previously known phenotypes associated with TCSs in Salmonella were also confirmed. We have also uncovered phenotypic divergence between Salmonella serovars, as distinct phenotypes between S. Typhi and S. Typhimurium were identified for cpxR. This finding highlights the importance of specifically studying S. Typhi to understand its pathogenesis mechanisms and to develop strategies to potentially reduce typhoid infections. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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10 pages, 975 KiB

Open AccessArticle

Genetic Markers in S. Paratyphi C Reveal Primary Adaptation to Pigs

by Satheesh Nair, Maria Fookes, Craig Corton, Nicholas R. Thomson, John Wain and Gemma C. Langridge

Microorganisms 2020, 8(5), 657; https://doi.org/10.3390/microorganisms8050657 - 30 Apr 2020

Cited by 4 | Viewed by 2477

Abstract

Salmonella enterica with the identical antigenic formula 6,7:c:1,5 can be differentiated biochemically and by disease syndrome. One grouping, Salmonella Paratyphi C, is currently considered a typhoidal serovar, responsible for enteric fever in humans. The human-restricted typhoidal serovars (S. Typhi and Paratyphi A, [...] Read more.

Salmonella enterica with the identical antigenic formula 6,7:c:1,5 can be differentiated biochemically and by disease syndrome. One grouping, Salmonella Paratyphi C, is currently considered a typhoidal serovar, responsible for enteric fever in humans. The human-restricted typhoidal serovars (S. Typhi and Paratyphi A, B and C) typically display high levels of genome degradation and are cited as an example of convergent evolution for host adaptation in humans. However, S. Paratyphi C presents a different clinical picture to S. Typhi/Paratyphi A, in a patient group with predisposition, raising the possibility that its natural history is different, and that infection is invasive salmonellosis rather than enteric fever. Using whole genome sequencing and metabolic pathway analysis, we compared the genomes of 17 S. Paratyphi C strains to other members of the 6,7:c:1,5 group and to two typhoidal serovars: S. Typhi and Paratyphi A. The genome degradation observed in S. Paratyphi C was much lower than S. Typhi/Paratyphi A, but similar to the other 6,7:c:1,5 strains. Genomic and metabolic comparisons revealed little to no overlap between S. Paratyphi C and the other typhoidal serovars, arguing against convergent evolution and instead providing evidence of a primary adaptation to pigs in accordance with the 6,7:c:1.5 strains. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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22 pages, 3513 KiB

Open AccessArticle

Salmonella Pathogenicity Island 1 (SPI-1): The Evolution and Stabilization of a Core Genomic Type Three Secretion System

by Nicole A. Lerminiaux, Keith D. MacKenzie and Andrew D. S. Cameron

Microorganisms 2020, 8(4), 576; https://doi.org/10.3390/microorganisms8040576 - 16 Apr 2020

Cited by 22 | Viewed by 6965

Abstract

Salmonella Pathogenicity Island 1 (SPI-1) encodes a type three secretion system (T3SS), effector proteins, and associated transcription factors that together enable invasion of epithelial cells in animal intestines. The horizontal acquisition of SPI-1 by the common ancestor of all Salmonella is considered a [...] Read more.

Salmonella Pathogenicity Island 1 (SPI-1) encodes a type three secretion system (T3SS), effector proteins, and associated transcription factors that together enable invasion of epithelial cells in animal intestines. The horizontal acquisition of SPI-1 by the common ancestor of all Salmonella is considered a prime example of how gene islands potentiate the emergence of new pathogens with expanded niche ranges. However, the evolutionary history of SPI-1 has attracted little attention. Here, we apply phylogenetic comparisons across the family Enterobacteriaceae to examine the history of SPI-1, improving the resolution of its boundaries and unique architecture by identifying its composite gene modules. SPI-1 is located between the core genes fhlA and mutS, a hotspot for the gain and loss of horizontally acquired genes. Despite the plasticity of this locus, SPI-1 demonstrates stable residency of many tens of millions of years in a host genome, unlike short-lived homologous T3SS and effector islands including Escherichia ETT2, Yersinia YSA, Pantoea PSI-2, Sodalis SSR2, and Chromobacterium CPI-1. SPI-1 employs a unique series of regulatory switches, starting with the dedicated transcription factors HilC and HilD, and flowing through the central SPI-1 regulator HilA. HilA is shared with other T3SS, but HilC and HilD may have their evolutionary origins in Salmonella. The hilA, hilC, and hilD gene promoters are the most AT-rich DNA in SPI-1, placing them under tight control by the transcriptional repressor H-NS. In all Salmonella lineages, these three promoters resist amelioration towards the genomic average, ensuring strong repression by H-NS. Hence, early development of a robust and well-integrated regulatory network may explain the evolutionary stability of SPI-1 compared to T3SS gene islands in other species. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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14 pages, 3162 KiB

Open AccessArticle

The Not so Good, the Bad and the Ugly: Differential Bacterial Adhesion and Invasion Mediated by Salmonella PagN Allelic Variants

by Yanping Wu, Qiaoyun Hu, Ruchika Dehinwal, Alexey V. Rakov, Nicholas Grams, Erin C. Clemens, Jennifer Hofmann, Iruka N. Okeke and Dieter M. Schifferli

Microorganisms 2020, 8(4), 489; https://doi.org/10.3390/microorganisms8040489 - 30 Mar 2020

Cited by 8 | Viewed by 3465

Abstract

While advances in genomic sequencing have highlighted significant strain variability between and within Salmonella serovars, only a few protein variants have been directly related to evolutionary adaptation for survival, such as host specificity or differential virulence. The current study investigated whether allelic variation [...] Read more.

While advances in genomic sequencing have highlighted significant strain variability between and within Salmonella serovars, only a few protein variants have been directly related to evolutionary adaptation for survival, such as host specificity or differential virulence. The current study investigated whether allelic variation of the Salmonella adhesin/invasin PagN influences bacterial interaction with their receptors. The Salmonella enterica, subspecies enterica serovar Typhi (S. Typhi) allelic variant of PagN was found to bind significantly better to different enterocytes as well as to the extracellular matrix protein laminin than did the major Salmonella enterica, subspecies enterica serovar Typhimurium (S. Typhimurium) allele. The two alleles differed at amino acid residues 49 and 109 in two of the four predicted PagN surface loops, and residue substitution analysis revealed that a glutamic acid at residue 49 increased the adhesive and invasive properties of S. Typhi PagN. PagN sequence comparisons from 542 Salmonella strains for six representative S. enterica serovars and S. diarizonae further supported the role of glutamic acid at residues 49 and 109 in optimizing adhesion to cells and laminin, as well as for cell invasion. In summary, this study characterized unique residues in allelic variants of a virulence factor that participates in the colonization and invasive properties of different Salmonella stains, subspecies and serovars. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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19 pages, 3445 KiB

Open AccessArticle

Salmonella Extracellular Polymeric Substances Modulate Innate Phagocyte Activity and Enhance Tolerance of Biofilm-Associated Bacteria to Oxidative Stress

by Mark M. Hahn and John S. Gunn

Microorganisms 2020, 8(2), 253; https://doi.org/10.3390/microorganisms8020253 - 13 Feb 2020

Cited by 21 | Viewed by 3352

Abstract

Salmonella enterica serovar Typhi causes 14.3 million acute cases of typhoid fever that are responsible for 136,000 deaths each year. Chronic infections occur in 3%–5% of those infected and S. Typhi persists primarily in the gallbladder by forming biofilms on cholesterol gallstones, but [...] Read more.

Salmonella enterica serovar Typhi causes 14.3 million acute cases of typhoid fever that are responsible for 136,000 deaths each year. Chronic infections occur in 3%–5% of those infected and S. Typhi persists primarily in the gallbladder by forming biofilms on cholesterol gallstones, but how these bacterial communities evade host immunity is not known. Salmonella biofilms produce several extracellular polymeric substances (EPSs) during chronic infection, which are hypothesized to prevent pathogen clearance either by protecting biofilm-associated bacteria from direct humoral attack or by modulating innate phagocyte interaction with biofilms. Using wild-type and EPS-deficient planktonic and biofilm Salmonella, the direct attack hypothesis was tested by challenging biofilms with human serum and antimicrobial peptides. Biofilms were found to be tolerant to these molecules, but these phenotypes were independent of the tested EPSs. By examining macrophage and neutrophil responses, new roles for biofilm-associated capsular polysaccharides and slime polysaccharides were identified. The S. Typhi Vi antigen was found to modulate innate immunity by reducing macrophage nitric oxide production and neutrophil reactive oxygen species (ROS) production. The slime polysaccharides colanic acid and cellulose were found to be immune-stimulating and represent a key difference between non-typhoidal serovars and typhoidal serovars, which do not express colanic acid. Furthermore, biofilm tolerance to the exogenously-supplied ROS intermediates hydrogen peroxide (H₂O₂) and hypochlorite (ClO⁻) indicated an additional role of the capsular polysaccharides for both serovars in recalcitrance to H₂O₂ but not ClO⁻, providing new understanding of the stalemate that arises during chronic infections and offering new directions for mechanistic and clinical studies. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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Review

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25 pages, 1860 KiB

Open AccessReview

Iron-Uptake Systems of Chicken-Associated Salmonella Serovars and Their Role in Colonizing the Avian Host

by Dinesh H. Wellawa, Brenda Allan, Aaron P. White and Wolfgang Köster

Microorganisms 2020, 8(8), 1203; https://doi.org/10.3390/microorganisms8081203 - 07 Aug 2020

Cited by 13 | Viewed by 5846

Abstract

Iron is an essential micronutrient for most bacteria. Salmonella enterica strains, representing human and animal pathogens, have adopted several mechanisms to sequester iron from the environment depending on availability and source. Chickens act as a major reservoir for Salmonella enterica strains which can [...] Read more.

Iron is an essential micronutrient for most bacteria. Salmonella enterica strains, representing human and animal pathogens, have adopted several mechanisms to sequester iron from the environment depending on availability and source. Chickens act as a major reservoir for Salmonella enterica strains which can lead to outbreaks of human salmonellosis. In this review article we summarize the current understanding of the contribution of iron-uptake systems to the virulence of non-typhoidal S. enterica strains in colonizing chickens. We aim to address the gap in knowledge in this field, to help understand and define the interactions between S. enterica and these important hosts, in comparison to mammalian models. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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23 pages, 2023 KiB

Open AccessReview

Spheres of Influence: Insights into Salmonella Pathogenesis from Intestinal Organoids

by Smriti Verma, Stefania Senger, Bobby J. Cherayil and Christina S. Faherty

Microorganisms 2020, 8(4), 504; https://doi.org/10.3390/microorganisms8040504 - 01 Apr 2020

Cited by 16 | Viewed by 6241

Abstract

The molecular complexity of host-pathogen interactions remains poorly understood in many infectious diseases, particularly in humans due to the limited availability of reliable and specific experimental models. To bridge the gap between classical two-dimensional culture systems, which often involve transformed cell lines that [...] Read more.

The molecular complexity of host-pathogen interactions remains poorly understood in many infectious diseases, particularly in humans due to the limited availability of reliable and specific experimental models. To bridge the gap between classical two-dimensional culture systems, which often involve transformed cell lines that may not have all the physiologic properties of primary cells, and in vivo animal studies, researchers have developed the organoid model system. Organoids are complex three-dimensional structures that are generated in vitro from primary cells and can recapitulate key in vivo properties of an organ such as structural organization, multicellularity, and function. In this review, we discuss how organoids have been deployed in exploring Salmonella infection in mice and humans. In addition, we summarize the recent advancements that hold promise to elevate our understanding of the interactions and crosstalk between multiple cell types and the microbiota with Salmonella. These models have the potential for improving clinical outcomes and future prophylactic and therapeutic intervention strategies. Full article

(This article belongs to the Special Issue Salmonella: Pathogenesis and Host Restriction)

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