Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Santander, Javier; Roland, Kenneth L.; Curtiss, Roy

doi:10.3855/jidc.154

Cited by 14 publications

(2 citation statements)

References 77 publications

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“…Although the location of the bands observed in the WB assay for IgG antibody isotypes was analogous, a clear diference in terms of the degree of antigenic intensity was demonstrated in the WB assay whereby PTS demonstrated a higher intensity of reaction compared to PHPS. In addition, a number of reports in the literature have delineated the presence and reactivity of Salmonella fagellin antigen with the expected molecular weight of 55 kDa [28][29][30]. In this study, the 55 kDa antigen was also detected in PTS-and PHPS-pooled serum against the IgG antibody isotype.…”

Section: Discussionsupporting

confidence: 50%

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Khan

Kader

2023

Interdisciplinary Perspectives on Infectious Diseases

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Typhoid fever is a multiorgan infectious disease caused by Salmonella typhi. It is transmitted through fecal oral route and can be fatal without proper treatment. Therefore, early diagnosis of typhoid fever is crucial. In the previous study, we have developed TYPHOIDYNE EIA, which showed excellent synergy between the genus conserved and species-specific antigens in the serodiagnosis of typhoid fever. TYPHOIDYNE EIA can effectively detect and differentiate typhoid patients, typhoid vaccinated subjects, healthy subjects, and subjects with other febrile illnesses. Following the successful development of TYPHOIDYNE EIA, in this report, we further characterize the antigenic components of differentially extracted S. typhi and S. spp recognized by IgM, IgG, and IgA antibody isotypes in typhoid patients and possible typhoid carrier by the western blot (WB) assay. The WB characterization revealed a dynamic pattern of recognition, with significant variations in the number of antigenic bands observed between the differentially extracted arrays of antigens. The reactivity of patient’s sera was divided into 3 regions, with region 1 (≥55 kDa) showing the strongest reactivity followed by region 2 (54 kDa–34 kDa) and region 3 (<34 kDa). Overall, the good synergy expressed in these bands suggests the potential role of these proteins in differentiating typhoid patients with possible typhoid carrier. The antigenic bands highlighted in this study are also identified as prospective biomarkers for diagnostic use and vaccine development.

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Section: Discussionsupporting

confidence: 50%

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Khan

Kader

2023

Interdisciplinary Perspectives on Infectious Diseases

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“…OmpR was first identified in E. coli as modulator of relative levels of major outer membrane proteins like OmpC and OmpF (Taylor et al, 1981) and, subsequently reported to be a positive regulator of the Salmonellapathogenicity island-2 (SPI-2) that modulates the S. Typhimurium intracellular lifestyle (Feng et al, 2003;Garmendia et al, 2003;Lee et al, 2000). OmpR has also been reported to control in a positive or negative manner the expression of virulence factors in other pathogens like enterohemorrhagic E. coli (Wang et al, 2021), S. Typhi (Santander et al, 2008), or Vibrio cholerae (Kunkle et al, 2020). Our findings extent this view and catalogue OmpR as a key regulator of PG metabolism and morphogenesis when S. Typhimurium colonizes the intracellular niche of eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

Salmonella exploits OmpR to switch essential morphogenetic peptidoglycan synthases in response to intracellular cues

López-Escarpa

Castanheira

Portillo

2021

Preprint

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Essential peptidoglycan synthases, like penicillin binding proteins 2 and 3 (PBP2/PBP3) of Escherichia coli, define shape by orchestrating cell elongation and division, respectively. Despite being intensively studied as drug targets, the regulatory rules governing their production remain poorly understood. During infection, the closely related pathogen Salmonella enterica serovar Typhimurium downregulates PBP2/PBP3 production and replace them with alternative peptidoglycan synthases, PBP2SAL/PBP3SAL, absent in E. coli. The bases for such switch in morphogenetic proteins are unknown. Here, we show that the S. Typhimurium regulator OmpR triggers PBP2SAL and PBP3SAL expression responding solely to acid pH and define a shared motif present in upstream regions of the PBP2SAL- and PBP3SAL-coding genes sufficient for such control. The elimination of PBP2/PBP3 in infection conditions is however multifactorial, requiring acidity, high osmolarity and being favoured by OmpR and the Prc protease. Remarkably, we found that E. coli loses the essential PBP3 required for cell division when exposed to both acidity and high osmolarity, the environmental cues encountered by intracellular S. Typhimurium. Therefore, OmpR played a central role in the evolution of this pathogen when co-opting the regulation of PBP2SAL/PBP3SAL and, consequently, promoting a new morphogenetic cycle that made possible increasing progeny inside acidic eukaryotic phagosomes.SignificanceSome enzymes that participate in peptidoglycan metabolism are present exclusively in bacterial pathogens and modify its structure to limit immune recognition. The intracellular pathogen Salmonella enterica serovar Typhimurium is the only example known to date in which a “substitution” of essential peptidoglycan enzymes involved in cell division and elongation takes place during infection. The data presented here support instability of PBP3 in environments with acidity and high osmolarity as a probable selective pressure that promoted the fixation of alternative morphogenetic enzymes. This was possible due to the control that OmpR exerted over these new foreign functions. The acquisition of enzymes like PBP2SAL and PBP3SAL therefore represent a “quantum leap” evolutionary event in S. Typhimurium that made possible the colonization of acidic intracellular niches.

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Reciprocal Regulation of OmpR and Hfq and Their Regulatory Actions on the Vi Polysaccharide Capsular Antigen in Salmonella enterica Serovar Typhi

et al. 2018

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Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of human typhoid fever. S. Typhi expresses a major virulence determinant called Vi polysaccharide capsular antigen, which is encoded by the viaB locus containing 10 consecutive genes including tviA and tviB. Expression of Vi antigen is regulated by the two-component regulatory system EnvZ/OmpR and the global RNA-binding factor Hfq. In this study, we show that OmpR coordinates with Hfq to regulate the transcription of Vi antigen genes under osmotic stress conditions. OmpR binds to the promoters of tviA and its own genes to activate their transcription; however, it positively regulates tviB and negatively regulates hfq in an indirect manner. Moreover, Hfq reversely inhibits ompR, tviA and tviB, and positively regulates its own gene expression. Thus, we report of a complex gene regulatory network involving the reciprocal regulation and autoregulation of OmpR and Hfq, and their regulatory actions on Vi polysaccharide capsular antigen genes in S. Typhi.

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Regulation of Vi Capsular Polysaccharide Synthesis in Salmonella enterica Serotype Typhi

Cited by 14 publications

References 77 publications

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Salmonella exploits OmpR to switch essential morphogenetic peptidoglycan synthases in response to intracellular cues

Reciprocal Regulation of OmpR and Hfq and Their Regulatory Actions on the Vi Polysaccharide Capsular Antigen in Salmonella enterica Serovar Typhi

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