Biomaterial Database

Contribution of typhoid toxin in the pathogenesis of Salmonella Typhi. 2022

Reena Thakur, and Chander Raman Suri, and Praveen Rishi

Department of Microbiology, Panjab University, Chandigarh, India.

To persist and establish infection, Salmonella utilizes a battery of different virulence determinants at every stage of infection. Typhoid toxin, a newly identified toxin in Salmonella enterica serovar Typhi is recognized as one of the virulence factors that has been linked with Salmonella pathogenesis. In this study, we have further investigated the role of typhoid toxin in the symptomatology of typhoid fever through in-vivo and ex-vivo studies. In mice, administration of cloned and purified typhoid toxin induces similar symptoms observed during typhoid fever such as fever, weight loss with a decrease in peripheral leucocyte count along with an increase in levels of pro-inflammatory cytokines (Il-6, TNF-α). Results of DNA analysis, fluorescence microscopy and flow cytometry of typhoid toxin-treated macrophages (ex-vivo) altogether revealed the CdtB (subunit of typhoid toxin) mediated DNA damage that led to the apoptosis of cells. Furthermore, to validate CdtB's catalytic role, macrophages were treated with typhoid toxin preincubated with anti-CdtB antibodies (generated in mice). Re-assessment of macrophage DNA by gel electrophoresis and flow cytometry analysis indicated a significant decrease in DNA damage and cells undergoing apoptosis, respectively. Moreover, a significant reduction in in-vitro DNase activity of CdtB protein was also observed on preincubating holotoxin with anti-CdtB antibodies. In total, this study highlights the role of typhoid toxin in inducing typhoid fever-like symptomatology, which may be executed through the toxin's catalytic subunit CdtB.

UI	MeSH Term	Description	Entries
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012475	Salmonella	A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility.
D012485	Salmonella typhi	A serotype of SALMONELLA ENTERICA which is the etiologic agent of TYPHOID FEVER.	Salmonella enterica serovar Typhi,Salmonella typhosa
D014435	Typhoid Fever	An acute systemic febrile infection caused by SALMONELLA TYPHI, a serotype of SALMONELLA ENTERICA.	Enteric Fever,Typhus, Abdominal,Salmonella typhi Infection,Typhoid,Abdominal Typhus,Enteric Fevers,Fever, Enteric,Fever, Typhoid,Fevers, Enteric,Fevers, Typhoid,Infection, Salmonella typhi,Infections, Salmonella typhi,Salmonella typhi Infections,Typhoid Fevers,Typhoids
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D037521	Virulence Factors	Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486)	Pathogenicity Factor,Pathogenicity Factors,Virulence Factor,Factor, Pathogenicity,Factor, Virulence,Factors, Pathogenicity,Factors, Virulence