scholarly journals Deciphering the Origins and Tracking the Evolution of Cholera Epidemics with Whole-Genome-Based Molecular Epidemiology

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Yonatan H. Grad ◽  
Matthew K. Waldor
Keyword(s):  
Point Mutations ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Cholera Outbreak ◽  
Outbreak Strain ◽  
Security Forces ◽  
Content Type ◽  
Cholera Epidemic ◽  
Genomic Analyses ◽  
The World

ABSTRACT The devastating Haitian cholera outbreak that began in October 2010 is the first known cholera epidemic in this island nation. Epidemiological and genomic data have provided strong evidence that United Nations security forces from Nepal introduced toxigenic Vibrio cholerae O1, the cause of epidemic cholera, to Haiti shortly before the outbreak arose. However, some have contended that indigenous V. cholerae contributed to the outbreak. In a recent paper (mBio 4:e00398-13, 2013), L. S. Katz et al. explored the nature and rate of changes in this ancient pathogen’s genome during an outbreak, based on whole-genome sequencing of 23 Haitian V. cholerae clinical isolates obtained over a 20-month period. Notably, they detected point mutations, deletions, and inversions but found no insertion of horizontally transmitted DNA, arguing strongly against the idea that autochthonous V. cholerae donated DNA to the outbreak strain. Furthermore, they found that Haitian epidemic V. cholerae isolates were virtually untransformable. Comparative genomic analyses revealed that the Haitian isolates were nearly identical to isolates from Nepal and that the Nepalese-Haitian isolates were distinguishable from isolates circulating elsewhere in the world. Reconstruction of the phylogeny of the Haitian isolates was consistent with a single introduction of V. cholerae to Haiti sometime between late July and late October 2010, dates remarkably concordant with epidemiological observations. In aggregate, this paper provides additional compelling evidence that the V. cholerae strain responsible for the Haitian cholera epidemic came from Nepal and illustrates the power of whole-genome-based analyses for epidemiology, pathogen evolution, and forensics.

scholarly journals Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Julia V. Bugrysheva ◽  
David Sue ◽  
Jay E. Gee ◽  
Mindy G. Elrod ◽  
Alex R. Hoffmaster ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Clavulanic Acid ◽  
Burkholderia Pseudomallei ◽  
Efflux Pump ◽  
Point Mutations ◽  
Comparative Genomic ◽  
Content Type ◽  
Reductase Gene ◽  
Amoxicillin Clavulanic Acid ◽  
Imipenem Resistance

ABSTRACT Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and β-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). We sequenced, assembled, and annotated the Bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A β-lactamase and was previously implicated in resistance to β-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance and T147A contributed to amoxicillin-clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei. Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely because of a frameshift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in the development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis.

scholarly journals Changing Molecular Epidemiology of Vibrio cholerae Outbreaks in Shanghai, China

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Dalong Hu ◽  
Zhiqiu Yin ◽  
Chao Yuan ◽  
Pan Yang ◽  
Chengqian Qian ◽  
...  
Keyword(s):  
Southeast Asia ◽  
East Asia ◽  
Vibrio Cholerae ◽  
Watery Diarrhea ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
The World ◽  
Pandemic Strains

ABSTRACT The 7th cholera pandemic began in 1961 in Sulawesi, Indonesia, and then spread around the world in at least three waves. However, the lack of genome sequences for Vibrio cholerae strains under long-term surveillance in East Asia, especially in China, has restricted our understanding of the dynamics of the intracountry and intercountry evolution and transmission of the 7th-pandemic clones. In this study, we obtained the genome sequences of 60 V. cholerae strains isolated in Shanghai, the largest port in the world and the largest city in China, from 1961 to 2011. Our whole-genome-based phylogeny of 7th-pandemic strains revealed that all but one fell into five “stages,” most of which are single clades and share independent ancestors. Each stage dominated in succession for a period, with little overlap between them. In addition, two near-identical Shanghai strains belonging to a pre-7th-pandemic precursor and 4 nontoxigenic O1/O139 strains attributed to independent recombination events at the O-antigen loci were present. The major lineages of the 7th pandemic in Shanghai appeared to be closely related to V. cholerae strains isolated from South or Southeast Asia. Stage succession was consistently related to changes in society and human activity, implying that human-caused niche change may play a vital role in the cholera dynamics in Shanghai. IMPORTANCE V. cholerae is the causative agent of cholera, a life-threatening disease characterized by severe, watery diarrhea. The 7th pandemic started in Indonesia in 1961 and spread globally, currently infecting 1.3 million to 4 million people annually. Here, we applied whole-genome sequencing to analyze a long-term collection of V. cholerae clinical strains to reveal the phylogenetic background and evolutionary dynamics of the 7th pandemic in Shanghai, which had undergone breathtakingly rapid development in the last half-century. All but one of the Shanghai 7th-pandemic strains fell into five “stages” that were dominant in Shanghai and appeared to be closely related to 7th-pandemic strains of South or Southeast Asia. Our findings extended the understanding of the dynamics of the evolution and transmission of the 7th-pandemic clones in East Asia and the relationship between social changes and cholera epidemiology.

scholarly journals Streptococcus gallolyticus subsp. gallolyticus from Human and Animal Origins: Genetic Diversity, Antimicrobial Susceptibility, and Characterization of a Vancomycin-Resistant Calf Isolate Carrying avanA-Tn1546-Like Element

2015 ◽  
Vol 59 (4) ◽  
pp. 2006-2015 ◽  
Author(s):  
Beatriz Romero-Hernández ◽  
Ana P. Tedim ◽  
José Francisco Sánchez-Herrero ◽  
Pablo Librado ◽  
Julio Rozas ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Antibiotic Susceptibility ◽  
Resistant Isolate ◽  
Comparative Genomic ◽  
Gene Gain ◽  
Whole Genome ◽  
Content Type ◽  
Streptococcus Gallolyticus

ABSTRACTThe aim of this work was to characterize the antibiotic susceptibility and genetic diversity of 41Streptococcus gallolyticussubsp.gallolyticusisolates: 18 isolates obtained from animals and 23 human clinical isolates. Antibiotic susceptibility was determined by the semiautomatic Wider system and genetic diversity by pulsed-field gel electrophoresis (PFGE) with SmaI. Animal isolates grouped separately in the PFGE analysis, but no statistical differences in antimicrobial resistance were found between the two groups. The LMG 17956 sequence type 28 (ST28) strain recovered from the feces of a calf exhibited high levels of resistance to vancomycin and teicoplanin (MIC, ≥256 mg/liter). Its glycopeptide resistance mechanism was characterized by Southern blot hybridization and a primer-walking strategy, and finally its genome, determined by whole-genome sequencing, was compared with four closely relatedS. gallolyticussubsp.gallolyticusgenomes. Hybridization experiments demonstrated that a Tn1546-like element was integrated into the bacterial chromosome. In agreement with this finding, whole-genome sequencing confirmed a partial deletion of thevanY-vanZregion and partial duplication of thevanHgene. The comparative genomic analyses revealed that the LMG 17956 ST28 strain had acquired an unusually high number of transposable elements and had experienced extensive chromosomal rearrangements, as well as gene gain and loss events. In conclusion,S. gallolyticussubsp.gallolyticusisolates from animals seem to belong to lineages separate from those infecting humans. In addition, we report a glycopeptide-resistant isolate from a calf carrying a Tn1546-like element integrated into its chromosome.

scholarly journals Whole-Genome Sequences and Classification of Streptococcus agalactiae Strains Isolated from Laboratory-Reared Long-Evans Rats (Rattus norvegicus)

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
C. Bodi Winn ◽  
J. Dzink-Fox ◽  
Y. Feng ◽  
Z. Shen ◽  
V. Bakthavatchalu ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Genomic Analysis ◽  
Opportunistic Pathogen ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
Long Evans ◽  
Fatal Septicemia

ABSTRACT In collaboration with the CDC’s Streptococcus Laboratory, we report here the whole-genome sequences of seven Streptococcus agalactiae bacteria isolated from laboratory-reared Long-Evans rats. Four of the S. agalactiae isolates were associated with morbidity accompanied by endocarditis, metritis, and fatal septicemia, providing an opportunity for comparative genomic analysis of this opportunistic pathogen.

Economic gloom portends instability in Zimbabwe

2016 ◽  
Keyword(s):  
South African ◽  
World Bank ◽  
Driving Force ◽  
Security Forces ◽  
Content Type ◽  
Regional Market ◽  
The World Bank ◽  
The World ◽  
The Government ◽  
South African Rand

Significance Mawarire is the founder of the 'This Flag' movement, which has been a driving force behind a wave of demonstrations and strikes earlier this month against graft, unemployment and economic mismanagement by President Robert Mugabe's government. Impacts Import bans will adversely affect South African exporters, for whom Zimbabwe is a key regional market. Use of the South African rand in Zimbabwe will remain unpopular, due to concerns about its weakness against the dollar. The government will prioritise cash for paying the salaries of the security forces, since these underpin the regime's survival. Loans from the African Export-Import Bank will help Harare to begin paying the World Bank some of its arrears.

scholarly journals Genomic Epidemiology of the Haitian Cholera Outbreak: a Single Introduction Followed by Rapid, Extensive, and Continued Spread Characterized the Onset of the Epidemic

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Mark Eppinger ◽  
Talima Pearson ◽  
Sara S. K. Koenig ◽  
Ofori Pearson ◽  
Nathan Hicks ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Whole Genome Sequence ◽  
Epidemiological Surveillance ◽  
Molecular Evidence ◽  
Whole Genome ◽  
Cholera Outbreak ◽  
Content Type ◽  
Genomic Epidemiology ◽  
Southern Asia ◽  
Strain Collection

ABSTRACT For centuries, cholera has been one of the most feared diseases. The causative agent Vibrio cholerae is a waterborne Gram-negative enteric pathogen eliciting a severe watery diarrheal disease. In October 2010, the seventh pandemic reached Haiti, a country that had not experienced cholera for more than a century. By using whole-genome sequence typing and mapping strategies of 116 serotype O1 strains from global sources, including 44 Haitian genomes, we present a detailed reconstructed evolutionary history of the seventh pandemic with a focus on the Haitian outbreak. We catalogued subtle genomic alterations at the nucleotide level in the genome core and architectural rearrangements from whole-genome map comparisons. Isolates closely related to the Haitian isolates caused several recent outbreaks in southern Asia. This study provides evidence for a single-source introduction of cholera from Nepal into Haiti followed by rapid, extensive, and continued clonal expansion. The phylogeographic patterns in both southern Asia and Haiti argue for the rapid dissemination of V. cholerae across the landscape necessitating real-time surveillance efforts to complement the whole-genome epidemiological analysis. As eradication efforts move forward, phylogeographic knowledge will be important for identifying persistent sources and monitoring success at regional levels. The results of molecular and epidemiological analyses of this outbreak suggest that an indigenous Haitian source of V. cholerae is unlikely and that an indigenous source has not contributed to the genomic evolution of this clade. IMPORTANCE In this genomic epidemiology study, we have applied high-resolution whole-genome-based sequence typing methodologies on a comprehensive set of genome sequences that have become available in the aftermath of the Haitian cholera epidemic. These sequence resources enabled us to reassess the degree of genomic heterogeneity within the Vibrio cholerae O1 serotype and to refine boundaries and evolutionary relationships. The established phylogenomic framework showed how outbreak isolates fit into the global phylogeographic patterns compared to a comprehensive globally and temporally diverse strain collection and provides strong molecular evidence that points to a nonindigenous source of the 2010 Haitian cholera outbreak and refines epidemiological standards used in outbreak investigations for outbreak inclusion/exclusion following the concept of genomic epidemiology. The generated phylogenomic data have major public health relevance in translating sequence-based information to assist in future diagnostic, epidemiological, surveillance, and forensic studies of cholera.

scholarly journals Diversity and Population Overlap between Avian and HumanEscherichia coliBelonging to Sequence Type 95

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Steffen L. Jørgensen ◽  
Marc Stegger ◽  
Eglé Kudirkiene ◽  
Berit Lilje ◽  
Louise L. Poulsen ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Large Scale ◽  
Sequence Type ◽  
Comparative Genomic ◽  
Avian Host ◽  
Whole Genome ◽  
Content Type ◽  
E Coli ◽  
Tract Infections

ABSTRACTAvian-pathogenicEscherichia coli(APEC) is a subgroup of extraintestinal pathogenicE.coli(ExPEC) presumed to be zoonotic and to represent an external reservoir for extraintestinal infections in humans, including uropathogenicE. coli(UPEC) causing urinary tract infections. Comparative genomics has previously been applied to investigate whether APEC and human ExPEC are distinct entities. Even so, whole-genome-based studies are limited, and large-scale comparisons focused on single sequence types (STs) are not available yet. In this study, comparative genomic analysis was performed on 323 APEC and human ExPEC genomes belonging to sequence type 95 (ST95) to investigate whether APEC and human ExPEC are distinct entities. Our study showed that APEC of ST95 did not constitute a unique ExPEC branch and was genetically diverse. A large genetic overlap between APEC and certain human ExPEC was observed, with APEC located on multiple branches together with closely related human ExPEC, including nearly identical APEC and human ExPEC. These results illustrate that certain ExPEC clones may indeed have the potential to cause infection in both poultry and humans. Previously described ExPEC-associated genes were found to be encoded on ColV plasmids. These virulence-associated plasmids seem to be crucial for ExPEC strains to cause avian colibacillosis and are strongly associated with strains of the mixed APEC/human ExPEC clusters. The phylogenetic analysis revealed two distinct branches consisting of exclusively closely related human ExPEC which did not carry the virulence-associated plasmids, emphasizing a lower avian virulence potential of human ExPEC in relation to an avian host.IMPORTANCEAPEC causes a range of infections in poultry, collectively called colibacillosis, and is the leading cause of mortality and is associated with major economic significance in the poultry industry. A growing number of studies have suggested APEC as an external reservoir of human ExPEC, including UPEC, which is a reservoir. ExPEC belonging to ST95 is considered one of the most important pathogens in both poultry and humans. This study is the first in-depth whole-genome-based comparison of ST95E. coliwhich investigates both the core genomes as well as the accessory genomes of avian and human ExPEC. We demonstrated that multiple lineages of ExPEC belonging to ST95 exist, of which the majority may cause infection in humans, while only part of the ST95 cluster seem to be avian pathogenic. These findings further support the idea that urinary tract infections may be a zoonotic infection.

scholarly journals Genetic Determinants of Hydroxycinnamic Acid Metabolism in Heterofermentative Lactobacilli

2019 ◽  
Vol 86 (5) ◽  
Author(s):  
Gautam Gaur ◽  
Jee-Hwan Oh ◽  
Pasquale Filannino ◽  
Marco Gobbetti ◽  
Jan-Peter van Pijkeren ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Phenolic Acids ◽  
Phenolic Acid ◽  
Acid Metabolism ◽  
Hydroxycinnamic Acid ◽  
Hydroxycinnamic Acids ◽  
Comparative Genomic ◽  
Plant Metabolites ◽  
Content Type ◽  
Genomic Analyses

ABSTRACT Phenolic acids are among the most abundant phenolic compounds in edible parts of plants. Lactic acid bacteria (LAB) metabolize phenolic acids, but the enzyme responsible for reducing hydroxycinnamic acids to phenylpropionic acids (HcrB) was only recently characterized in Lactobacillus plantarum. In this study, heterofermentative LAB species were screened for their hydroxycinnamic acid metabolism. Data on strain-specific metabolism in combination with comparative genomic analyses identified homologs of HcrB as putative phenolic acid reductases. Par1 and HcrF both encode putative multidomain proteins with 25% and 63% amino acid identity to HcrB, respectively. Of these genes, par1 in L. rossiae and hcrF in L. fermentum were overexpressed in response to hydroxycinnamic acids. The deletion of par1 in L. rossiae led to the loss of phenolic acid metabolism. The strain-specific metabolism of phenolic acids was congruent with the genotype of lactobacilli; however, phenolic acid reductases were not identified in strains of Weissella cibaria that reduced hydroxycinnamic acids to phenylpropionic acids. Phylogenetic analysis of major genes involved in hydroxycinnamic acid metabolism in strains of the genus Lactobacillus revealed that Par1 was found to be the most widely distributed phenolic acid reductase, while HcrB was the least abundant, present in less than 9% of Lactobacillus spp. In conclusion, this study increased the knowledge on the genetic determinants of hydroxycinnamic acid metabolism, explaining the species- and strain-specific metabolic variations in lactobacilli and providing evidence of additional enzymes involved in hydroxycinnamic acid metabolism of lactobacilli. IMPORTANCE The metabolism of secondary plant metabolites, including phenolic compounds, by food-fermenting lactobacilli is a significant contributor to the safety, quality, and nutritional quality of fermented foods. The enzymes mediating hydrolysis, reduction, and decarboxylation of phenolic acid esters and phenolic acids in lactobacilli, however, are not fully characterized. The genomic analyses presented here provide evidence for three novel putative phenolic acid reductases. Matching comparative genomic analyses with phenotypic analysis and quantification of gene expression indicates that two of the three putative phenolic acid reductases, Par1 and HcrF, are involved in reduction of hydroxycinnamic acids to phenylpropionic acids; however, the activity of Par2 may be unrelated to phenolic acids and recognizes other secondary plant metabolites. These findings expand our knowledge on the metabolic potential of lactobacilli and facilitate future studies on activity and substrate specificity of enzymes involved in metabolism of phenolic compounds.

COVID-19 will embolden autocrats

2020 ◽  
Keyword(s):  
Human Rights ◽  
Sub Saharan Africa ◽  
Quality Of Democracy ◽  
Checks And Balances ◽  
Security Forces ◽  
Content Type ◽  
Human Rights Abuses ◽  
The World ◽  
Sub Saharan

Subject Democracy and COVID-19 Significance A growing number of leaders are using the COVID-19 pandemic as an opportunity to curtail the activities of opposition parties and to expand their powers. In some cases, such as Malawi, unpopular presidents are using a declaration of emergency to prohibit opposition rallies and protests. In others, such as Hungary, emergency laws have been introduced that effectively undermine democratic checks and balances. The need for lockdown and quarantine to contain the virus has also led to a militarisation of the healthcare response -- with significant human rights abuses already reported in Kenya, Rwanda and South Africa. Impacts Further power grabs are likely as the crisis's impact is increasingly felt in Sub-Saharan Africa. Human rights violations will increase as stretched security forces enforce lockdowns on populations that have limited trust in government. The quality of democracy in many parts of the world will continue to decline.

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