Draft Genome Sequences of Salmonella enterica Serovar Typhimurium LT2 with Deleted Chitinases That Are Emerging Virulence Factors

Arabyan, Narine; Huang, Bihua C.; Weimer, Bart C.

doi:10.1128/genomea.00659-17

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…However, for this analysis to succeed, a substantial genome sequence database, of isolates collected across time and geographic location, was needed to enable placement in a phylogenetic context 28 , 29 . As outbreaks are bound to happen in the future, investment in cataloguing the genomic space of pathogens is even more important than previously appreciated so that populations of appropriate size can be examined as systematically examined in bacteria 30 , 31 . It is critical to obtain COVID-19 sequences from humans as well as other animals that have zoonotic potential.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of SARS-CoV-2 genomic epidemiology reveals disease transmission coupled to variant emergence and allelic variation

Bandoy

Weimer

2021

Sci Rep

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The spread of SARS-CoV-2 created a pandemic crisis with > 150,000 cumulative cases in > 65 countries within a few months. The reproductive number (R) is a metric to estimate the transmission of a pathogen during an outbreak. Preliminary published estimates were based on the initial outbreak in China. Whole genome sequences (WGS) analysis found mutational variations in the viral genome; however, previous comparisons failed to show a direct relationship between viral genome diversity, transmission, and the epidemic severity. COVID-19 incidences from different countries were modeled over the epidemic curve. Estimates of the instantaneous R (Wallinga and Teunis method) with a short and standard serial interval were done. WGS were used to determine the populations genomic variation and that underpinned creation of the pathogen genome identity (GENI) score, which was merged with the outbreak curve in four distinct phases. Inference of transmission time was based on a mutation rate of 2 mutations/month. R estimates revealed differences in the transmission and variable infection dynamics between and within outbreak progression for each country examined. Outside China, our R estimates observed propagating dynamics indicating that other countries were poised to move to the takeoff and exponential stages. Population density and local temperatures had no clear relationship to the outbreak progression. Integration of incidence data with the GENI score directly predicted increases in cases as the genome variation increased that led to new variants. Integrating the outbreak curve, dynamic R, and SNP variation found a direct association between increasing cases and transmission genome evolution. By defining the epidemic curve into four stages and integrating the instantaneous country-specific R with the GENI score, we directly connected changes in individual outbreaks based on changes in the virus genome via SNPs. This resulted in the ability to forecast potential increases in cases as well as mutations that may defeat PCR screening and the infection process. By using instantaneous R estimations and WGS, outbreak dynamics were defined to be linked to viral mutations, indicating that WGS, as a surveillance tool, is required to predict shifts in each outbreak that will provide actionable decision making information. Integrating epidemiology with genome sequencing and modeling allows for evidence-based disease outbreak tracking with predictive therapeutically valuable insights in near real time.

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Section: Discussionmentioning

confidence: 99%

“…This was demonstrated previously with zoonotic Campylobacter species 32 , 33 that enabled disease in a variety of host species. Creating sequence repositories for pathogens is critical and underway for various pathogens 31 as well as SARS-CoV-2 21 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of SARS-CoV-2 genomic epidemiology reveals disease transmission coupled to variant emergence and allelic variation

Bandoy

Weimer

2021

Sci Rep

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“…Two chitinases present in the genome of S . Typhimurium LT2 (NCBI: NC_003197.2), STM0018 (ChiA; GeneID:1251536) and STM0233 (GeneID: 1251751), have been recently proposed as potential virulence factors [ 7 ]. Our study uses the ATCC 14028 strain of S .…”

Section: Introductionmentioning

confidence: 99%

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion

et al. 2022

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Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome.

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“…Many of these virulence factors have been studied in detail, while others are continuously being discovered. Two chitinases present in the genome of Salmonella LT2, STM0018 (ChiA) and STM0233, have been recently proposed as potential virulence factors [7]. Our study uses the ATCC 14028 strain of Salmonella, which has the genomic identifier STM14_0022 and STM14_0275 for chiA and STM0233, respectively.…”

Section: Introductionmentioning

confidence: 99%

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion

Devlin

Santus

Mendez

et al. 2021

Preprint

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Salmonella enterica serovar Typhimurium ( Salmonella ) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, Salmonella produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species and the Salmonella genome contains two annotated chitinases: STM0018 ( chiA ) and STM0233. However, the role of these chitinases during Salmonella pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. Salmonella lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinasedeficient Salmonella strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed Salmonella dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type Salmonella , suggesting that chitinases are secreted. By analyzing N -linked glycans of small intestinal cells, we identified specific N -acetylglucosamine-containing glycans as potential extracellular targets of Salmonella chitinases. This analysis also revealed differential abundance of Lewis X-containing glycans that is likely a result of host cell modulation due to the detection of Salmonella chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that Salmonella chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome.

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Draft Genome Sequences of Salmonella enterica Serovar Typhimurium LT2 with Deleted Chitinases That Are Emerging Virulence Factors

Cited by 4 publications

References 24 publications

Analysis of SARS-CoV-2 genomic epidemiology reveals disease transmission coupled to variant emergence and allelic variation

Analysis of SARS-CoV-2 genomic epidemiology reveals disease transmission coupled to variant emergence and allelic variation

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion

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