Chronic Salmonella Typhi carriage at sites other than the gallbladder

Hoffman, Seth A; Sikorski, Michael J.; Levine, Myron M.

doi:10.1371/journal.pntd.0011168

Cited by 8 publications

(2 citation statements)

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“…The gallbladder and the biliary tract are the primary sites in the human body for the chronic carriage of typhoidal serovars of S. enterica (Hoffman et al, 2023). The diagnosis of the majority of the individuals with chronic carriage of persistent S. Typhi with gallstones and cholecystitis (chronic inflammation of the gallbladder)…”

Section: Persistent Infection and Its Role In Amrmentioning

confidence: 99%

Defying the odds: Determinants of the antimicrobial response of Salmonella Typhi and their interplay

Chowdhury,

Mukherjee,

Chatterjee

et al. 2023

Molecular Microbiology

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Salmonella Typhi, the invasive serovar of S. enterica subspecies enterica, causes typhoid fever in healthy human hosts. The emergence of antibiotic‐resistant strains has consistently challenged the successful treatment of typhoid fever with conventional antibiotics. Antimicrobial resistance (AMR) in Salmonella is acquired either by mutations in the genomic DNA or by acquiring extrachromosomal DNA via horizontal gene transfer. In addition, Salmonella can form a subpopulation of antibiotic persistent (AP) cells that can survive at high concentrations of antibiotics. These have reduced the effectiveness of the first and second lines of antibiotics used to treat Salmonella infection. The recurrent and chronic carriage of S. Typhi in human hosts further complicates the treatment process, as a remarkable shift in the immune response from pro‐inflammatory Th1 to anti‐inflammatory Th2 is observed. Recent studies have also highlighted the overlap between AP, persistent infection (PI) and AMR. These incidents have revealed several areas of research. In this review, we have put forward a timeline for the evolution of antibiotic resistance in Salmonella and discussed the different mechanisms of the same availed by the pathogen at the genotypic and phenotypic levels. Further, we have presented a detailed discussion on Salmonella antibiotic persistence (AP), PI, the host and bacterial virulence factors that can influence PI, and how both AP and PI can lead to AMR.

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Section: Persistent Infection and Its Role In Amrmentioning

confidence: 99%

Defying the odds: Determinants of the antimicrobial response of Salmonella Typhi and their interplay

Chowdhury,

Mukherjee,

Chatterjee

et al. 2023

Molecular Microbiology

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“…S . Typhi also reach the gallbladder hematogenously during primary bacteremia or shortly thereafter through infected hepatic bile entering the gallbladder ( 11 , 12 ). S .…”

Section: Introductionmentioning

confidence: 99%

SalmonellaTyphi Haplotype 58 (H58) Biofilm Formation and Genetic Variation in Typhoid Fever Patients with Gallstones in an Endemic Setting in Kenya

Muturi,

Wachira,

Wagacha

et al. 2024

Preprint

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The causative agent of typhoid fever,Salmonella entericaserovar Typhi, is a human restricted pathogen. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, butS. Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify biofilm forming ability and the genetic differences in longitudinal clinicalS. Typhi isolates from asymptomatic carriers with gallstones in Nairobi, Kenya. Whole genome sequences were analyzed from 22S. Typhi isolates, 20 from stool and 2 from blood samples, all genotype 4.3.1 (H58). Nineteen strains were from four patients also diagnosed with gallstones, of whom, three had typhoid symptoms and continued to shedS. Typhi after treatment. All isolates had point mutations in the quinolone resistance determining region (QRDR) and only sub-lineage 4.3.1.2EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR), isolates formed significantly stronger biofilmsin vitrothan the MDR isolates, p<0.001. A point mutation within thetreBgene (treBA383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. Missense mutations in Vi capsular polysaccharide genes,tviEP263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes and genetic variations inS.Typhi from asymptomatic carriers.ImportanceAlthough typhoid fever has largely been eliminated in high income countries, it remains a major global public health concern especially among low- and middle-income countries. The bacteria responsible for this infectious disease,SalmonellaTyphi, has limited ability to replicate outside the human host and human carriers serve as a reservoir of infection. Typhoid is a common infection in parts of sub-Saharan Africa and Asia, and is endemic in our study setting. Our research findings on differences inS.Typhi strains causing typhoid fever and carriage will influence public health approaches aimed at reducing carriage and transmission ofS. Typhi.

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