Characterization of Anti-Salmonella enterica Serotype Typhi Antibody Responses in Bacteremic Bangladeshi Patients by an Immunoaffinity Proteomics-Based Technology

ABSTRACT Salmonella enterica serotype Typhi is the cause of typhoid fever and a human-restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform immunoaffinity proteomics-based technology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S. Typhi to capture S. Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S. Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S. Typhi and S. Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S. Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays.

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Typhoid Fever due to Extended Spectrum β-Lactamase-Producing Salmonella enterica Serovar Typhi: A Case Report and Literature Review

Case Reports in Infectious Diseases ◽

10.1155/2018/4610246 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Abdul Azeez Ahamed Riyaaz ◽

Vindya Perera ◽

Sabaratnam Sivakumaran ◽

Nelun de Silva

Keyword(s):

Case Report ◽

Sri Lanka ◽

Typhoid Fever ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhi ◽

Extended Spectrum ◽

Cephalosporin Resistance ◽

Resistant Strains ◽

Derivatives Of

Emergence of cephalosporin-resistant strains of Salmonella enterica serovar Typhi is a cause of concern in the management of enteric fever. Cephalosporin resistance in Salmonella species is mainly due to the production of extended-spectrum β-lactamases (ESBLs). The majority of ESBLs in Salmonella enterica serovar Typhi are derivatives of the TEM, SHV, and CTX-M β-lactamase families. Of these, CTX-M appears to be predominant. This paper discusses the detection and molecular characterization of an ESBL-producing Salmonella enterica serovar Typhi strain isolated from a patient who was admitted to a private hospital in Sri Lanka. The three main types of β-lactamases such as TEM, SHV, and CTX-M were identified in this isolate. This case report from Sri Lanka contributes to the knowledge of the increasingly reported cases of typhoid fever due to Salmonella enterica serovar Typhi resistant to β-lactamase by ESBL production.

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In silico secretome characterization of clinical Mycobacterium abscessus isolates provides insights into antigenic differences

10.1101/2020.10.22.349720 ◽

2020 ◽

Author(s):

Fernanda Cornejo-Granados ◽

Thomas A. Kohl ◽

Flor Vásquez Sotomayor ◽

Sönke Andres ◽

Rogelio Hernández-Pando ◽

...

Keyword(s):

Drug Targets ◽

Reference Strain ◽

Mycobacterium Abscessus ◽

Bioinformatics Pipeline ◽

Diagnostic Assays ◽

Essential Proteins ◽

Immunogenic Proteins ◽

Drugbank Database

AbstractMycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. ES proteins contain highly immunogenic proteins, which are of interest for novel diagnostic assays and vaccines. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and fifteen clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. We found that ~18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85 % of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independently of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php).

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A Review on Recent Developments for the Cure of Salmonella Enterica Serovar Typhi, the Causative Agent for Typhoid Fever

THE JOURNAL OF MICROBIOLOGY AND MOLECULAR GENETICS ◽

10.52700/jmmg.v1i2.13 ◽

2020 ◽

Vol 1 (2) ◽

pp. 1-8

Author(s):

Muqadas Kanwal ◽

Fadia Waheed ◽

Hafsa Shahzadi ◽

Muhammad Shahbaz ◽

Ahsan Noor

Keyword(s):

Typhoid Fever ◽

Salmonella Enterica ◽

Enteric Fever ◽

Ethical Issues ◽

Age Groups ◽

Human Infection ◽

Health Concern ◽

Typhoid Vaccine ◽

The World

Salmonella enterica typhi is typhoid or enteric fever agent which is a serious water-borne disease and is a human host restricted organism. So, an important cause of death in underdeveloped countries, typhoid fever is a public health concern. Worldwide, 15-30 million people suffer from this disease every year, causing more than 200,000 deaths. However, several lines of evidence suggest that the advent of multidrug-resistant non-typhoidal strains of Salmonella has an important impact on the effectiveness of current strategies, including reductions in the effectiveness of early empirical treatment for controlling and managing foodborne diseases. Recent studies show more than 2000 strains of salmonella bacteria with around 100 strains connected to human infection - with myriad common strains from Salmonella Heidelberg to Typhimurium to Salmonella infantis. The multi-medicinal strain S. Typhi H58 has developed into the main circulating strain in many parts of the world, and an extensively drug-resistant (XDR) subclade has been recently found. Most of the people agree that the most effective way to control infection is to vaccinate susceptible populations. The commercially available live attenuated (Ty21a) vaccine, on the other hand, is not recommendable for children under the age of six, whereas the poor long-term efficacy of Vi-polysaccharide-based vaccine against typhoid fever. Furthermore, there are no vaccines available to protect against S. para typhi infection. Subsequently, a new formulation is urgently needed that can provide long-term protection against both pathogens while healthy for all age groups. Pakistan is the first country in the world to incorporate the WHO-recommended conjugate vaccine into its routine typhoid immunization program (2019). As a result, the purpose of this review is to describe the various diagnostic procedures for typhoid fever diagnosis and cure development. This article addressed some of the elements and components required for the implementation of typhoid vaccine. With an analysis of past and current enteric fever vaccines in progress as well as the ethical issues relevant to CHIM in typhoid vaccine efficacy research, we have combined the new methods to predict typhoid burden and vaccines impact.

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Characterization of Basal Transcriptomes Identifies Potential Metabolic and Virulence-Associated Adaptations Among Diverse Nontyphoidal Salmonella enterica Serovars

Frontiers in Microbiology ◽

10.3389/fmicb.2021.730411 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alexa R. Cohn ◽

Renato H. Orsi ◽

Laura M. Carroll ◽

Ruixi Chen ◽

Martin Wiedmann ◽

...

Keyword(s):

Salmonella Enterica ◽

Luria Bertani ◽

Human Infection ◽

Whole Genome Sequence ◽

Rna Seq ◽

Late Exponential Phase ◽

Zoonotic Pathogen ◽

Severity Of Disease ◽

Core Genes

The zoonotic pathogen Salmonella enterica includes >2,600 serovars, which differ in the range of hosts they infect and the severity of disease they cause. To further elucidate the mechanisms behind these differences, we performed transcriptomic comparisons of nontyphoidal Salmonella (NTS) serovars with the model for NTS pathogenesis, S. Typhimurium. Specifically, we used RNA-seq to characterize the understudied NTS serovars S. Javiana and S. Cerro, representing a serovar frequently attributed to human infection via contact with amphibians and reptiles, and a serovar primarily associated with cattle, respectively. Whole-genome sequence (WGS) data were utilized to ensure that strains characterized with RNA-seq were representative of their respective serovars. RNA extracted from representative strains of each serovar grown to late exponential phase in Luria-Bertani (LB) broth showed that transcript abundances of core genes were significantly higher (p<0.001) than those of accessory genes for all three serovars. Inter-serovar comparisons identified that transcript abundances of genes in Salmonella Pathogenicity Island (SPI) 1 were significantly higher in both S. Javiana and S. Typhimurium compared to S. Cerro. Together, our data highlight potential transcriptional mechanisms that may facilitate S. Cerro and S. Javiana survival in and adaptation to their respective hosts and impact their ability to cause disease in others. Furthermore, our analyses demonstrate the utility of omics approaches in advancing our understanding of the diversity of metabolic and virulence mechanisms of different NTS serovars.

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Antibodies in Action: Role of Human Opsonins in Killing Salmonella enterica Serovar Typhi

Infection and Immunity ◽

10.1128/iai.05081-11 ◽

2011 ◽

Vol 79 (8) ◽

pp. 3188-3194 ◽

Cited By ~ 27

Author(s):

Janet C. Lindow ◽

Kelly A. Fimlaid ◽

Janice Y. Bunn ◽

Beth D. Kirkpatrick

Keyword(s):

Typhoid Fever ◽

Salmonella Enterica ◽

Functional Characterization ◽

Serum Samples ◽

Content Type ◽

Bactericidal Antibody ◽

Antibody Titers ◽

Future Work

ABSTRACTAlthough vaccines have been available for over a century, a correlate of protection for typhoid fever has yet to be identified. Antibodies are produced in response to typhoid infection and vaccination and are generally used as the gold standard for determining vaccine immunogenicity, even though their role in clearance ofSalmonella entericaserovar Typhi infections is poorly defined. Here, we describe the first functional characterization ofS.Typhi-specific antibodies following vaccination with a new vaccine, M01ZH09 (Ty2 ΔaroCΔssaV). We determined that postvaccination sera increased the uptake of wild-typeS.Typhi by human macrophages up to 2.3-fold relative to prevaccination (day 0) or placebo samples. These results were recapitulated using immunoglobulins purified from postvaccination serum, demonstrating that antibodies were largely responsible for increases in uptake. Imaging verified that macrophages internalized 2- to 9.5-fold moreS.Typhi when the bacteria were opsonized with postvaccination sera than when the bacteria were opsonized with day 0 or placebo sera. Once inside macrophages, the survival ofS.Typhi was reduced as much as 50% when opsonized with postvaccination sera relative to day 0 or placebo serum samples. Lastly, bactericidal assays indicated that antibodies generated postvaccination were recognized by complement factors and assisted in killingS.Typhi: mean postvaccination bactericidal antibody titers were higher at all time points than placebo and day 0 titers. These data clearly demonstrate that there are at least two mechanisms by which antibodies facilitate killing ofS.Typhi. Future work could lead to improved immunogenicity tests associated with vaccine efficacy and the identification of correlates of protection against typhoid fever.

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