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Annual Review of Microbiology 2014Salmonella enterica serovar Typhi, the cause of typhoid, is host restricted to humans. S. Typhi has a monophyletic population structure, indicating that typhoid in... (Review)
Review
Salmonella enterica serovar Typhi, the cause of typhoid, is host restricted to humans. S. Typhi has a monophyletic population structure, indicating that typhoid in humans is a relatively new disease. Antimicrobial usage is reshaping the current S. Typhi global population and may be driving the emergence of a specific haplotype, H58, that is well adapted to transmission in modern settings and is able to resist antimicrobial killing more efficiently than other S. Typhi. Evidence gathered through genomics and functional studies using the mouse and in vitro cell systems, together with clinical investigations, has provided insight into the mechanisms that underpin the pathogenesis of human typhoid and host restriction. Here we review the latest scientific advances in typhoid research and discuss how these novel approaches are changing our understanding of the disease.
Topics: Animals; Anti-Bacterial Agents; Humans; Salmonella typhi; Serogroup; Typhoid Fever
PubMed: 25208300
DOI: 10.1146/annurev-micro-091313-103739 -
Tropical Medicine & International... Aug 2017Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding... (Review)
Review
Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development.
Topics: Biological Evolution; Drug Resistance, Microbial; Genome, Bacterial; Humans; Phylogeny; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 28544285
DOI: 10.1111/tmi.12899 -
Advances in Experimental Medicine and... 2016Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening bacterial infection that is very common in the developing world. Recent... (Review)
Review
Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening bacterial infection that is very common in the developing world. Recent spread of antimicrobial resistant isolates of S. Typhi makes typhoid fever, a global public health risk. Despite being a common disease, still very little is known about the molecular mechanisms underlying typhoid fever and S. Typhi pathogenesis. In contrast to other Salmonellae, S. Typhi can only infect humans. The molecular bases of this human restriction are mostly unknown. Recent studies identified a novel pathway that contributes to S. Typhi human restriction and is required for killing S. Typhi in macrophages of nonsusceptible species. The small Rab GTPase Rab32 and its guanine nucleotide exchange factor BLOC-3 are the critical components of this pathway. These proteins were already well known as important regulators of intracellular membrane transport. In particular, they are central for the transport of enzymes that synthetize melanin in pigment cells. The recent findings that Rab32 and BLOC-3 are required for S. Typhi host restriction point out to a novel mechanism restricting the growth of bacterial pathogen, dependent on the transport of still unknown molecule(s) to the S. Typhi vacuole. The identification of this novel antimicrobial pathway constitutes a critical starting point to study molecular mechanisms killing bacterial pathogens and possibly identify novel antimicrobial molecules.
Topics: Animals; Guanine Nucleotide Exchange Factors; Host-Pathogen Interactions; Humans; Macrophages; Salmonella typhi; Signal Transduction; Typhoid Fever; Vacuoles; Virulence; rab GTP-Binding Proteins
PubMed: 27193549
DOI: 10.1007/978-3-319-32189-9_17 -
Advances in Experimental Medicine and... 2018Typhoid is a major global disease. The causative agent, Salmonella enterica serovar Typhi (S. Typhi) has a capsular antigen called Vi antigen which is traditionally... (Review)
Review
Typhoid is a major global disease. The causative agent, Salmonella enterica serovar Typhi (S. Typhi) has a capsular antigen called Vi antigen which is traditionally considered to be the main cause of virulence. All the current vaccines are based on Vi antigen. However, the realization of the fact that there are S. Typhi strains which lack Vi antigen but still exist naturally and can cause disease has stirred great scientific interest. It is also interesting to note that their relative prevalence is affected by climatic conditions. Now it is established that Vi positive and Vi negative S. Typhi have different modes of pathogenesis; and as recent studies suggest, different structure of polysaccharide antigens. This means that current vaccines are not effective against a significant number of S. Typhi strains which not only affect the success of vaccination programs but also help in rapid emergence of Vi negative S. Typhi due to natural selection. The focus should be on vaccines based on antigens which are universally present in all S. Typhi. One such candidate is O-specific polysaccharides (OSPs). Successful attempts have been made to prepare conjugate vaccines based on OSPs.
Topics: Animals; Bacterial Vaccines; Humans; Polysaccharides, Bacterial; Salmonella typhi; Typhoid Fever; Virulence
PubMed: 29785477
DOI: 10.1007/978-981-10-7572-8_2 -
The Journal of Infectious Diseases Dec 2021In 2016, a whole-genome sequence (WGS)-based genotyping framework (GenoTyphi) was developed and provided a phylogenetically informative nomenclature for lineages of... (Review)
Review
In 2016, a whole-genome sequence (WGS)-based genotyping framework (GenoTyphi) was developed and provided a phylogenetically informative nomenclature for lineages of Salmonella Typhi, the etiological agent of typhoid fever. Subsequent surveillance studies have revealed additional epidemiologically important subpopulations, which require the definition of new genotypes and extension of associated software to facilitate the detection of antimicrobial resistance (AMR) mutations. Analysis of 4632 WGS provide an updated overview of the global S Typhi population structure and genotyping framework, revealing the widespread nature of haplotype 58 ([H58] 4.3.1) genotypes and the diverse range of genotypes carrying AMR mutations.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Genotype; Haplotypes; Humans; Phylogeny; Polymorphism, Single Nucleotide; Salmonella typhi; Typhoid Fever; Whole Genome Sequencing
PubMed: 34453548
DOI: 10.1093/infdis/jiab414 -
Clinical Infectious Diseases : An... Jul 2007The generation of complete genome sequences provides a blueprint that facilitates the genetic characterization of pathogens and their hosts. The genome of Salmonella... (Review)
Review
The generation of complete genome sequences provides a blueprint that facilitates the genetic characterization of pathogens and their hosts. The genome of Salmonella enterica serovar Typhi (S. Typhi) harbors ~5 million base pairs encoding some 4000 genes, of which >200 are functionally inactive. Comparison of S. Typhi isolates from around the world indicates that they are highly related (clonal) and that they emerged from a single point of origin ~30,000-50,000 years ago. Evidence suggests that, as well as undergoing gene degradation, S. Typhi has also recently acquired genes, such as those encoding the Vi antigen, by horizontal transfer events.
Topics: Antigens, Bacterial; Escherichia coli; Genome, Bacterial; Host-Parasite Interactions; Humans; Polysaccharides, Bacterial; Salmonella typhi; Salmonella typhimurium; Sequence Alignment; Sequence Analysis, DNA; Virulence
PubMed: 17582565
DOI: 10.1086/518143 -
PLoS Neglected Tropical Diseases Mar 2020Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding...
Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region.
Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Child; Child, Preschool; Colombia; Drug Resistance, Bacterial; Epidemiological Monitoring; Female; Genetic Variation; Genotype; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Retrospective Studies; Salmonella typhi; Sex Distribution; Typhoid Fever; Young Adult
PubMed: 32155148
DOI: 10.1371/journal.pntd.0008040 -
PLoS Neglected Tropical Diseases 2012Drug resistance of Salmonella enterica serovar Typhi (Salmonella Typhi) to first-line antibiotics is emerging in Central Africa. Although increased use of...
BACKGROUND
Drug resistance of Salmonella enterica serovar Typhi (Salmonella Typhi) to first-line antibiotics is emerging in Central Africa. Although increased use of fluoroquinolones is associated with spread of resistance, Salmonella Typhi with decreased ciprofloxacin susceptibility (DCS) has rarely been reported in Central Africa.
METHODOLOGY/PRINCIPAL FINDINGS
As part of a microbiological surveillance study in the Democratic Republic of the Congo (DR Congo), Salmonella Typhi isolates from bloodstream infections were collected prospectively between 2007 and 2011. The genetic relationship of the Salmonella Typhi isolates was assessed by pulsed-field gel electrophoresis (PFGE). The antimicrobial resistance profile of the isolates was determined and mutations associated with DCS were studied. In total, 201 Salmonella Typhi isolates were collected. More than half of the Salmonella Typhi isolates originated from children and young adults aged 5-19. Thirty different PFGE profiles were identified, with 72% of the isolates showing a single profile. Multidrug resistance, DCS and azithromycin resistance were 30.3%, 15.4% and 1.0%, respectively. DCS was associated with point mutations in the gyrA gene at codons 83 and 87.
CONCLUSIONS/SIGNIFICANCE
Our study describes the first report of widespread multidrug resistance and DCS among Salmonella Typhi isolates from DR Congo. Our findings highlight the need for increased microbiological diagnosis and surveillance in DR Congo, being a prerequisite for rational use of antimicrobials and the development of standard treatment guidelines.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Blood; Child; Child, Preschool; Democratic Republic of the Congo; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Fluoroquinolones; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Prevalence; Salmonella typhi; Typhoid Fever; Young Adult
PubMed: 23166855
DOI: 10.1371/journal.pntd.0001921 -
Virulence 2011The ability of bacterial pathogens to sense their immediate environment plays a significant role on their capacity to survive and cause disease. Salmonella enterica... (Review)
Review
The ability of bacterial pathogens to sense their immediate environment plays a significant role on their capacity to survive and cause disease. Salmonella enterica serovar typhi (S. typhi) is an exclusively human pathogen that causes typhoid fever. In a recent study, we have shown that S. typhi senses and responds to host neuroendocrine stress hormones to release the toxin hemolysin E. Hormone-mediated hemolysis by S. typhi was inhibited by the β-blocker propranolol and was dependent on the presence of the CpxAR signal transduction system. Furthermore, we demonstrate that normal expression of the small RNA micA is necessary for the arbitration of the response to host neuroendocrine hormones. This leads to a significant decrease in the levels of the outer membrane protein OmpA and increased formation of membrane vesicles containing HlyE. The exploration of host pathogen interactions is of paramount importance in deciphering pathogen virulence and the discovery of novel treatments.
Topics: Animals; Bacterial Proteins; Hemolysin Proteins; Hormones; Host-Pathogen Interactions; Humans; Neurosecretory Systems; Salmonella typhi; Typhoid Fever; Virulence
PubMed: 21758008
DOI: 10.4161/viru.2.4.16810 -
Journal of Medical Microbiology May 2018Ceftriaxone is the drug of choice for typhoid fever and the emergence of resistant Salmonella Typhi raises major concerns for treatment. There are an increasing number...
PURPOSE
Ceftriaxone is the drug of choice for typhoid fever and the emergence of resistant Salmonella Typhi raises major concerns for treatment. There are an increasing number of sporadic reports of ceftriaxone-resistant S. Typhi and limiting the risk of treatment failure in the patient and outbreaks in the community must be prioritized. This study describes the use of whole genome sequencing to guide outbreak identification and case management.
METHODOLOGY
An isolate of ceftriaxone-resistant S. Typhi from the blood of a child taken in 2000 at the Popular Diagnostic Center, Dhaka, Bangladesh was subjected to whole genome sequencing, using an Illumina NextSeq 500 and analysis using Geneious software.Results/Key findings. Comparison with other ceftriaxone-resistant S. Typhi revealed an isolate from the Democratic Republic of the Congo in 2015 as the closest relative but no evidence of an outbreak. A plasmid belonging to incompatibility group I1 (IncI1-ST31) which included blaCTX-M-15 (ceftriaxone resistance) associated with ISEcp-1 was identified. High similarity (90 %) was seen with pS115, an IncI1 plasmid from S. Enteritidis, and with pESBL-EA11, an incI1 plasmid from E. coli (99 %) showing that S. Typhi has access to ceftriaxone resistance through the acquisition of common plasmids.
CONCLUSIONS
The transmission of ceftriaxone resistance from E. coli to S. Typhi is of concern because of clinical resistance to ceftriaxone, the main stay of typhoid treatment. Whole genome sequencing, albeit several years after the isolation, demonstrated the success of containment but clinical trials with alternative agents are urgently required.
Topics: Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Child; Disease Outbreaks; Drug Resistance, Bacterial; Humans; Phylogeny; Plasmids; Salmonella typhi; Typhoid Fever; Whole Genome Sequencing; beta-Lactamases
PubMed: 29616895
DOI: 10.1099/jmm.0.000727