scholarly journals Microevolution ofStreptococcus agalactiaeST-261 from Australia Indicates Dissemination via Imported Tilapia and Ongoing Adaptation to Marine Hosts or Environment

2018 ◽  
Vol 84 (16) ◽  
Author(s):  
Minami Kawasaki ◽  
Jerome Delamare-Deboutteville ◽  
Rachel O. Bowater ◽  
Mark J. Walker ◽  
Scott Beatson ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Core Genome ◽  
Minimum Spanning Tree ◽  
Vaccine Development ◽  
The United States ◽  
Wild Fish ◽  
Clinical Isolates ◽  
Global Trade ◽  
Content Type ◽  
Wide Range

ABSTRACTStreptococcus agalactiae(group BStreptococcus[GBS]) causes disease in a wide range of animals. The serotype Ib lineage is highly adapted to aquatic hosts, exhibiting substantial genome reduction compared with terrestrial conspecifics. Here, we sequence genomes from 40 GBS isolates, including 25 isolates from wild fish and captive stingrays in Australia, six local veterinary or human clinical isolates, and nine isolates from farmed tilapia in Honduras, and compared them with 42 genomes from public databases. Phylogenetic analysis based on nonrecombinant core-genome single nucleotide polymorphisms (SNPs) indicated that aquatic serotype Ib isolates from Queensland were distantly related to local veterinary and human clinical isolates. In contrast, Australian aquatic isolates are most closely related to a tilapia isolate from Israel, differing by only 63 core-genome SNPs. A consensus minimum spanning tree based on core-genome SNPs indicates the dissemination of sequence type 261 (ST-261) from an ancestral tilapia strain, which is congruent with several introductions of tilapia into Australia from Israel during the 1970s and 1980s. Pangenome analysis identified 1,440 genes as core, with the majority being dispensable or strain specific, with non-protein-coding intergenic regions (IGRs) divided among core and strain-specific genes. Aquatic serotype Ib strains have lost many virulence factors during adaptation, but six adhesins were well conserved across the aquatic isolates and might be critical for virulence in fish and for targets in vaccine development. The close relationship among recent ST-261 isolates from Ghana, the United States, and China with the Israeli tilapia isolate from 1988 implicates the global trade in tilapia seed for aquaculture in the widespread dissemination of serotype Ib fish-adapted GBS.IMPORTANCEStreptococcus agalactiae(GBS) is a significant pathogen of humans and animals. Some lineages have become adapted to particular hosts, and serotype Ib is highly specialized to fish. Here, we show that this lineage is likely to have been distributed widely by the global trade in tilapia for aquaculture, with probable introduction into Australia in the 1970s and subsequent dissemination in wild fish populations. We report here the variability in the polysaccharide capsule among this lineage but identify a cohort of common surface proteins that may be a focus of future vaccine development to reduce the biosecurity risk in international fish trade.

scholarly journals Microevolution of aquaticStreptococcus agalactiaeST-261 from Australia indicates dissemination via imported tilapia and ongoing adaptation to marine hosts or environment

2018 ◽  
Author(s):  
Minami Kawasaki ◽  
Jerome Delamare-Deboutteville ◽  
Rachel O Bowater ◽  
Mark J Walker ◽  
Scott Beatson ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Core Genome ◽  
Minimum Spanning Tree ◽  
Vaccine Development ◽  
Wild Fish ◽  
Surface Proteins ◽  
Clinical Isolates ◽  
Global Trade ◽  
Wide Range ◽  
Intergenic Regions

AbstractStreptococcus agalactiae(GBS) causes disease in a wide range of animals. The serotype 1b lineage is highly adapted to aquatic hosts, exhibiting substantial genome reduction compared with terrestrial con-specifics. Here we sequence genomes from 40 GBS isolates including 25 from wild fish and captive stingrays in Australia, six local veterinary or human clinical isolates, and nine isolates from farmed tilapia in Honduras and compare with 42 genomes from public databases. Phylogenetic analysis based on non-recombinant core genome SNPs indicated that aquatic serotype Ib isolates from Queensland were distantly related to local veterinary and human clinical isolates. In contrast, Australian aquatic isolates are most closely related to a tilapia isolate from Israel, differing by only 63 core-genome SNPs. A consensus minimum spanning tree based on core genome SNPs indicates dissemination of ST-261 from an ancestral tilapia strain, which is congruent with several introductions of tilapia into Australia from Israel during the 1970s and 1980s. Pan-genome analysis identified 1,440 genes as core with the majority being dispensable or strain-specific with non-protein-coding intergenic regions (IGRs) divided amongst core and strain-specific genes. Aquatic serotype Ib strains have lost many virulence factors during adaptation, but six adhesins were well conserved across the aquatic isolates and might be critical for virulence in fish and targets for vaccine development. The close relationship amongst recent ST-261 isolates from Ghana, USA and China with the Israeli tilapia isolate from 1988 implicates the global trade in tilapia seed for aquaculture in the widespread dissemination of serotype Ib fish-adapted GBS.ImportanceStreptococcus agalactiae(GBS) is a significant pathogen of humans and animals. Some lineages have become adapted to particular hosts and serotype Ib is highly specialized to fish. Here we show that this lineage is likely to have been distributed widely by the global trade in tilapia for aquaculture, with probable introduction into Australia in the 1970s and subsequent dissemination in wild fish populations. We report variability in the polysaccharide capsule amongst this lineage, but identify a cohort common surface proteins that may be a focus of future vaccine development to reduce the biosecurity risk in international fish trade.

A review of policy, practices, and players governing and involved in the United States vaccine and immunization enterprise

2017 ◽  
Vol 22 (3) ◽  
pp. 138-151
Author(s):  
Angela K. Shen ◽  
Alice Y. Tsai ◽  
Guthrie S. Birkhead
Keyword(s):  
Public Health ◽  
Decision Making ◽  
Vaccine Development ◽  
The United States ◽  
Federal State ◽  
Content Type ◽  
Wide Range ◽  
The Us ◽  
The Usa ◽  
State And Local

Purpose The purpose of this paper is to outline the organization and governance of the US vaccine and immunization enterprise. It describes the major components of the US system including the various relationships between major federal government entities, stakeholders, and advisory committees that inform government policymaking at various points in the system. Design/methodology/approach The authors describe the complex interdependent network of partners that engage in a wide range of activities such as disease surveillance, research, vaccine development, regulatory licensure, practice recommendations, financing, service delivery, communications, and post-licensure monitoring. Findings The US system of governance is highly participatory and focuses on a transparent and open engagement, with input from a wide range of partners to inform decision-making. This collaborative framework allows many inputs to be heard and helps support the US vaccine and immunization system as it evolves to meet the continued public health needs in the USA through the optimal use of safe and effective vaccines. Originality/value This is an invited article on the US vaccine and immunization enterprise. The development and availability of vaccines in the USA has had profound impact on mortality and morbidity and public health (Centers for Disease Control and Prevention, 2011). The success of this enterprise is a result of a blended public and private sector system with partnerships at the federal, state, and local levels of government to optimize the use of safe and effective vaccines. Governance structures have been established to support the interaction and decision-making among the federal and non-federal actors toward the common goal of controlling and preventing infectious diseases.

scholarly journals New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters

2016 ◽  
Vol 82 (8) ◽  
pp. 2240-2246 ◽  
Author(s):  
Alex I. Kanno ◽  
Cibelly Goulart ◽  
Henrique K. Rofatto ◽  
Sergio C. Oliveira ◽  
Luciana C. C. Leite ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Fluorescent Protein ◽  
Vaccine Development ◽  
Expression Vectors ◽  
Content Type ◽  
Expression Levels ◽  
Wide Range ◽  
Mycobacteriophage L5 ◽  
Green Fluorescent ◽  
Selection Of

ABSTRACTThe expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such asMycobacterium bovisBCG orM. smegmatiswas made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinantM. smegmatisbacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in bothM. smegmatisandM. bovisBCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of theSchistosoma mansoniantigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response.

scholarly journals An Observational Cohort Study ofClostridium difficileRibotype 027 and Recurrent Infection

mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Krishna Rao ◽  
Peter D. R. Higgins ◽  
Vincent B. Young
Keyword(s):  
Logistic Regression ◽  
Independent Predictor ◽  
The United States ◽  
Public Health Issue ◽  
Clinical Microbiology Laboratory ◽  
Clinical Predictors ◽  
Content Type ◽  
Ribotype 027 ◽  
Increased Risk ◽  
Wide Range

ABSTRACTRecurrentClostridium difficileinfection (rCDI) frequently complicates recovery from CDI. Accurately predicting rCDI would allow judicious allocation of limited resources, but published models have met with limited success. Thus, biomarkers predictive of recurrence have been sought. This study tested whether PCR ribotype independently predicted rCDI. Stool samples from nonpregnant inpatients ≥18 years of age with diarrhea were included from October 2010 to January 2013 after the patients tested positive forC. difficilein the clinical microbiology laboratory. Per guidelines, the rCDI was defined as a positive test forC. difficileat >2 weeks but ≤8 weeks from the index episode. For each sample, a single colony ofC. difficilewas isolated by anaerobic culture, confirmed to be toxigenic by PCR, and ribotyped. Simple logistic regression and multiple logistic regression were used to model the primary outcome of rCDI, incorporating a wide range of clinical parameters. In total, 927 patients with 968 index episodes of CDI were included, with 110 (11.4%) developing rCDI. Age and use of proton pump inhibitors or concurrent antibiotics did not increase the risk of rCDI. Low serum bilirubin levels and ribotype 027 were associated with increased risk of rCDI on unadjusted analysis, with health care-associated CDI being inversely associated. In the final multivariable model, ribotype 027 was the strongest independent predictor of rCDI (odds ratio, 2.17; 95% confidence interval, 1.33 to 3.56;P= 0.002). Ribotype 027 is an independent predictor of rCDI.IMPORTANCECDI is a major public health issue, with over 400,000 cases per year in the United States alone. Recurrent CDI is common, occurring in approximately one in five individuals after a primary episode. Although interventions exist that could reduce the risk of recurrence, deployment in all patients is limited by cost, invasiveness, and/or an undetermined long-term safety profile. Thus, clinicians need risk stratification tools to properly allocate treatments. Because prior research on clinical predictors has failed to yield a reliable, reproducible, and effective predictive model to assist treatment decisions, accurate biomarkers of recurrence would be of great value. This study tested whether PCR ribotype independently predicted rCDI, and the data build upon prior research in showing that ribotype 027 is associated with rCDI.

Reforms will help clean up China's securities market

2021 ◽  
Keyword(s):  
Insider Trading ◽  
Stock Price ◽  
The United States ◽  
Securities Market ◽  
Foreign Firms ◽  
Financial Fraud ◽  
Content Type ◽  
Listed Firms ◽  
Wide Range ◽  
Political Priority

Significance China's securities market has grown dramatically, but the rules that underpin its functioning have failed to keep pace and have been poorly enforced because regulators and courts lacked resources and the issue was never a political priority. Insider trading, stock price manipulation and other fraud is relatively common. Impacts A wide range of sectors and institutions will need to adjust, including investors, listed firms, traders, law enforcers and courts. Foreign firms investing in China will benefit from better protection from financial fraud. China may send judges abroad to learn from other systems; Europe is a more likely destination than the United States.

scholarly journals Ceftobiprole Activity against Bacteria from Skin and Skin Structure Infections in the United States from 2016 through 2018

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Robert K. Flamm ◽  
Leonard R. Duncan ◽  
Kamal A. Hamed ◽  
Jennifer I. Smart ◽  
Rodrigo E. Mendes ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Generation Cephalosporin ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Highly Active

ABSTRACT Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), beta-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC50/90, 0.5/1 mg/liter; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [MRSA]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [ESBL] phenotype). A total of 74.4% of P. aeruginosa, 100% of beta-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/liter. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016 to 2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for a potential ABSSSI indication.

scholarly journals Draft Genome Sequences of Eight Vibrio sp. Clinical Isolates from across the United States That Form a Basal Sister Clade to Vibrio cholerae

2019 ◽  
Vol 8 (3) ◽  
Author(s):  
Kevin Liang ◽  
Mohammad Tarequl Islam ◽  
Nora Hussain ◽  
Nathan S. Winkjer ◽  
Monica S. Im ◽  
...  
Keyword(s):  
United States ◽  
Vibrio Cholerae ◽  
Draft Genome ◽  
The United States ◽  
Clinical Isolates ◽  
Genome Sequences ◽  
Content Type ◽  
Monophyletic Cluster ◽  
Sister Clade

We sequenced the genomes of eight isolates from various regions of the United States. These isolates form a monophyletic cluster clearly related to but distinct from Vibrio cholerae.

scholarly journals Serotype Distribution, Population Structure, and Antimicrobial Resistance of Group B Streptococcus Strains Recovered from Colonized Pregnant Women

2016 ◽  
Vol 55 (2) ◽  
pp. 412-422 ◽  
Author(s):  
Sarah Teatero ◽  
Patricia Ferrieri ◽  
Irene Martin ◽  
Walter Demczuk ◽  
Allison McGeer ◽  
...  
Keyword(s):  
Population Structure ◽  
Pregnant Women ◽  
Antimicrobial Agents ◽  
Vaccine Development ◽  
Group B Streptococcus ◽  
Tetracycline Resistance ◽  
The United States ◽  
High Rate ◽  
Content Type ◽  
Group B

ABSTRACTUsing serotyping, multilocus sequence typing, and whole-genome sequencing (WGS) of selected strains, we studied the population structure of 102 group BStreptococcus(GBS) isolates prospectively sampled in 2014 from vaginal/rectal swabs of healthy pregnant women in metropolitan Toronto, Canada. We also determined the susceptibilities of each of the colonizing isolates to penicillin, erythromycin, clindamycin, tetracycline, and other antimicrobial agents. Overall, we observed a high rate of tetracycline resistance (89%) among colonizing GBS isolates. We found resistance to erythromycin in 36% of the strains, and 33% were constitutively or inducibly resistant to clindamycin. The most frequently identified serotypes were III (25%), Ia (23%), and V (19%). Serotype IV accounted for 6% of the colonizing isolates, a rate consistent with that observed among patients with invasive GBS infections in metropolitan Toronto. The majority of serotype IV isolates belonged to sequence type (ST)459, a tetracycline-, erythromycin-, and clindamycin-resistant ST first identified in Minnesota, which is considered to be the main driver of serotype IV GBS expansion in North America. WGS revealed that ST459 isolates from Canada are clonally related to colonizing and invasive ST459 organisms circulating in regions of the United States. We also used WGS to study recombination in selected colonizing strains from metropolitan Toronto, which revealed multiple episodes of capsular switching. Present and future circulating GBS organisms and their genetic diversity may influence GBS vaccine development.

scholarly journals Staphylococcus epidermidis MSCRAMM SesJ Is Encoded in Composite Islands

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Srishtee Arora ◽  
Xiqi Li ◽  
Andrew Hillhouse ◽  
Kranti Konganti ◽  
Sara V. Little ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Staphylococcus Epidermidis ◽  
Core Genome ◽  
Clinical Isolates ◽  
Modification System ◽  
Content Type ◽  
Genes Encoding ◽  
Staphylococcal Cassette Chromosome

ABSTRACT Staphylococcus epidermidis is a leading cause of nosocomial infections in patients with a compromised immune system and/or an implanted medical device. Seventy to 90% of S. epidermidis clinical isolates are methicillin resistant and carry the mecA gene, present in a mobile genetic element (MGE) called the staphylococcal cassette chromosome mec (SCCmec) element. Along with the presence of antibiotic and heavy metal resistance genes, MGEs can also contain genes encoding secreted or cell wall-anchored virulence factors. In our earlier studies of S. epidermidis clinical isolates, we discovered S. epidermidis surface protein J (SesJ), a prototype of a recently discovered subfamily of the microbial surface component recognizing adhesive matrix molecule (MSCRAMM) group. MSCRAMMs are major virulence factors of pathogenic Gram-positive bacteria. Here, we report that the sesJ gene is always accompanied by two glycosyltransferase genes, gtfA and gtfB, and is present in two MGEs, called the arginine catabolic mobile element (ACME) and the staphylococcal cassette chromosome (SCC) element. The presence of the sesJ gene was associated with the left-hand direct repeat DR_B or DR_E. When inserted via DR_E, the sesJ gene was encoded in the SCC element. When inserted via DR_B, the sesJ gene was accompanied by the genes for the type 1 restriction modification system and was encoded in the ACME. Additionally, the SCC element and ACME carry different isoforms of the SesJ protein. To date, the genes encoding MSCRAMMs have been seen to be located in the bacterial core genome. Here, we report the presence of an MSCRAMM in an MGE in S. epidermidis clinical isolates. IMPORTANCE S. epidermidis is an opportunistic bacterium that has established itself as a successful nosocomial pathogen. The modern era of novel therapeutics and medical devices has extended the longevity of human life, but at the same time, we also witness the evolution of pathogens to adapt to newly available niches in the host. Increasing antibiotic resistance among pathogens provides an example of such pathogen adaptation. With limited opportunities to modify the core genome, most of the adaptation occurs by acquiring new genes, such as virulence factors and antibiotic resistance determinants present in MGEs. In this study, we describe that the sesJ gene, encoding a recently discovered cell wall-anchored protein in S. epidermidis, is present in both ACME and the SCC element. The presence of virulence factors in MGEs can influence the virulence potential of a specific strain. Therefore, it is critical to study the virulence factors found in MGEs in emerging pathogenic bacteria or strains to understand the mechanisms used by these bacteria to cause infections.

scholarly journals Comparative Surveillance Study of Telavancin Activity against Recently Collected Gram-Positive Clinical Isolates from across the United States

2008 ◽  
Vol 52 (7) ◽  
pp. 2383-2388 ◽  
Author(s):  
Deborah C. Draghi ◽  
Bret M. Benton ◽  
Kevin M. Krause ◽  
Clyde Thornsberry ◽  
Chris Pillar ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Clinical Isolates ◽  
Surveillance Study ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Serious Infections ◽  
Wide Range ◽  
Vancomycin Resistant

ABSTRACT Telavancin is an investigational, rapidly bactericidal lipoglycopeptide antibiotic that is being developed to treat serious infections caused by gram-positive bacteria. A baseline prospective surveillance study was conducted to assess telavancin activity, in comparison with other agents, against contemporary clinical isolates collected from 2004 to 2005 from across the United States. Nearly 4,000 isolates were collected, including staphylococci, enterococci, and streptococci (pneumococci, beta-hemolytic, and viridans). Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range, 0.03 to 1.0 μg/ml), independent of resistance to methicillin or to multiple agents. Telavancin activity was particularly potent against all streptococcal groups (MIC90s, 0.03 to 0.12 μg/ml). Telavancin had excellent activity against vancomycin-susceptible enterococci (MIC90, 1 μg/ml) and was active against VanB strains of vancomycin-resistant enterococci (MIC90, 2 μg/ml) but less active against VanA strains (MIC90, 8 to 16 μg/ml). Telavancin also demonstrated activity against vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains (MICs, 0.5 μg/ml to 1.0 μg/ml and 1.0 μg/ml to 4.0 μg/ml, respectively). These data may support the efficacy of telavancin for treatment of serious infections with a wide range of gram-positive organisms.

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