scholarly journals Molecular Analyses of TEM Genes and Their Corresponding Penicillinase-Producing Neisseria gonorrhoeae Isolates in Bangkok, Thailand

2011 ◽  
Vol 56 (2) ◽  
pp. 916-920 ◽  
Author(s):  
Shu-ichi Nakayama ◽  
Chanwit Tribuddharat ◽  
Sasiprapa Prombhul ◽  
Ken Shimuta ◽  
Somporn Srifuengfung ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Sexual Network ◽  
Genetic Event ◽  
Content Type ◽  
Extended Spectrum ◽  
Resistance To Penicillin ◽  
High Level ◽  
International Awareness

ABSTRACTNeisseria gonorrhoeaeis a major public health problem globally, especially because the bacterium has developed resistance to most antimicrobials introduced for first-line treatment of gonorrhea. In the present study, 96N. gonorrhoeaeisolates with high-level resistance to penicillin from 121 clinical isolates in Thailand were examined to investigate changes related to their plasmid-mediated penicillin resistance and their molecular epidemiological relationships. A β-lactamase (TEM) gene variant,blaTEM-135, that may be a precursor in the transitional stage of a traditionalblaTEM-1gene into an extended-spectrum β-lactamase (ESBL), possibly causing high resistance to all extended-spectrum cephalosporins inN. gonorrhoeae, was identified. Clonal analysis using multilocus sequence typing (MLST) andN. gonorrhoeaemultiantigen sequence typing (NG-MAST) revealed the existence of a sexual network among patients from Japan and Thailand. Molecular analysis of theblaTEM-135gene showed that the emergence of this allele might not be a rare genetic event and that the allele has evolved in different plasmid backgrounds, which results possibly indicate that it is selected due to antimicrobial pressure. The presence of theblaTEM-135allele in the penicillinase-producingN. gonorrhoeaepopulation may call for monitoring for the possible emergence of ESBL-producingN. gonorrhoeaein the future. This study identified ablaTEMvariant (blaTEM-135) that is a possible intermediate precursor for an ESBL, which warrants international awareness.

scholarly journals Trends and Risk Factors for Antimicrobial-Resistant Neisseria gonorrhoeae, Melbourne, Australia, 2007 to 2018

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Deborah A. Williamson ◽  
Christopher K. Fairley ◽  
Benjamin P. Howden ◽  
Marcus Y. Chen ◽  
Kerrie Stevens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neisseria Gonorrhoeae ◽  
Laboratory Data ◽  
Northeast Asia ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
International Travel ◽  
Major Public Health Problem ◽  
Comprehensive Overview ◽  
Content Type

ABSTRACT Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health problem. Traditionally, AMR surveillance programs for N. gonorrhoeae have focused mainly on laboratory data to describe the prevalence and trends of resistance. However, integrating individual-level risk factors (e.g., sexual orientation or international travel) with laboratory data provides important insights into factors promoting the spread of resistant N. gonorrhoeae. Here, over a 12-year period, we assessed the trends and risk factors for resistant N. gonorrhoeae in individuals attending a large publicly funded sexual health center in Melbourne, Australia. A total of 7,588 N. gonorrhoeae isolates were cultured from 5,593 individuals between 1 January 2007 and 31 December 2018. The proportion of isolates with penicillin resistance decreased from 49.5% in 2007 to 18.3% in 2018 (ptrend < 0.001) and from 63.5% in 2007 to 21.1% in 2018 for ciprofloxacin resistance (ptrend < 0.001). In contrast, the proportion of isolates displaying decreased susceptibility to ceftriaxone increased from 0.5% in 2007 to 2.9% in 2018 (ptrend < 0.001), with a significant increase in low-level azithromycin resistance, from 2.5% in 2012 to 8.2% in 2018 (ptrend < 0.001). Multivariate analysis identified risk factors for multidrug-resistant (MDR) N. gonorrhoeae, namely, female sex and country of birth, with MDR isolates more common in individuals born in northeast Asia, further highlighting the importance of this region and international travel as factors in the cross-border transmission of MDR N. gonorrhoeae. Future surveillance work should incorporate additional epidemiological and genomic data to provide a comprehensive overview of the emergence and spread of resistant N. gonorrhoeae.

Medically Important Vector Borne Disease Control-Botanical Plant Extract Trials

2018 ◽  
Vol 4 (4) ◽  
pp. 513
Author(s):  
Rakhshan .
Keyword(s):  
Disease Control ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Vector Borne Disease ◽  
Development Of Resistance ◽  
Vector Borne ◽  
Synthetic Pesticides ◽  
High Level ◽  
Continuous Use ◽  
Chemical Pesticides

Mosquitoes are vectors of many pathogens which causes serious human diseases like Malaria, Filariasis, Japanese encephalitis, Dengue fever, Chikungunya, Yellow fever and Zika virus which constitute a major public health problem globally. Mosquito borne diseases cause high level of economic impact all over the world and result in millions of death every year. They infect around 700,000,000 people annually worldwide and 40,000,000 only in India. The continuous use of synthetic pesticides to control vector mosquitoes has caused physiological resistance, toxic effect on human health, environmental pollution and addition to these, its adverse effects can be observed on non-target organisms. Synthetic chemical pesticides have been proved to be effective, but overall in last 5 decades indiscriminate use of synthetic pesticides against vector borne disease control have originated several ecological issues due to their residual accumulation and development of resistance in target vectors and their chronic effects.

scholarly journals Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

2014 ◽  
Vol 53 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Walter Demczuk ◽  
Tarah Lynch ◽  
Irene Martin ◽  
Gary Van Domselaar ◽  
Morag Graham ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Large Scale ◽  
Epidemiological Studies ◽  
23S Rrna ◽  
Genome Comparison ◽  
Whole Genome ◽  
Content Type ◽  
Genomic Epidemiology ◽  
High Level ◽  
Sequence Types

A large-scale, whole-genome comparison of CanadianNeisseria gonorrhoeaeisolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While someN. gonorrhoeaemultiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaicpenAalleles, followed in 2000/2001 with thepenAmosaic X allele and then in 2007 with ST1407 strains with thepenAmosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated withpenAmosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections.

scholarly journals Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae

2002 ◽  
Vol 184 (20) ◽  
pp. 5619-5624 ◽  
Author(s):  
Wendy L. Veal ◽  
Robert A. Nicholas ◽  
William M. Shafer
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Base Pair ◽  
Efflux Pump ◽  
Penicillin Resistance ◽  
Single Base ◽  
Base Pair Deletion ◽  
Resistance To Penicillin ◽  
Single Base Pair ◽  
High Level ◽  
Level Resistance

ABSTRACT The importance of the mtrCDE-encoded efflux pump in conferring chromosomally mediated penicillin resistance on certain strains of Neisseria gonorrhoeae was determined by using genetic derivatives of penicillin-sensitive strain FA19 bearing defined mutations (mtrR, penA, and penB) donated by a clinical isolate (FA6140) expressing high-level resistance to penicillin and antimicrobial hydrophobic agents (HAs). When introduced into strain FA19 by transformation, a single base pair deletion in the mtrR promoter sequence from strain FA6140 was sufficient to provide high-level resistance to HAs (e.g., erythromycin and Triton X-100) but only a twofold increase in resistance to penicillin. When subsequent mutations in penA and porIB were introduced from strain FA6140 into strain WV30 (FA19 mtrR) by transformation, resistance to penicillin increased incrementally up to a MIC of 1.0 μg/ml. Insertional inactivation of the gene (mtrD) encoding the membrane transporter component of the Mtr efflux pump in these transformant strains and in strain FA6140 decreased the MIC of penicillin by 16-fold. Genetic analyses revealed that mtrR mutations, such as the single base pair deletion in its promoter, are needed for phenotypic expression of penicillin and tetracycline resistance afforded by the penB mutation. As penB represents amino acid substitutions within the third loop of the outer membrane PorIB protein that modulate entry of penicillin and tetracycline, the results presented herein suggest that PorIB and the MtrC-MtrD-MtrE efflux pump act synergistically to confer resistance to these antibiotics.

scholarly journals Chromatin-Mediated Epigenetic Regulation in the Malaria Parasite Plasmodium falciparum

2010 ◽  
Vol 9 (8) ◽  
pp. 1138-1149 ◽  
Author(s):  
Liwang Cui ◽  
Jun Miao
Keyword(s):  
Gene Regulation ◽  
Plasmodium Falciparum ◽  
Cell Invasion ◽  
Posttranslational Modifications ◽  
Antigenic Variation ◽  
Public Health Problem ◽  
Specific Reference ◽  
Major Public Health Problem ◽  
Invasion Pathways ◽  
Content Type

ABSTRACT Malaria is a major public health problem in many developing countries, with the malignant tertian parasite Plasmodium falciparum causing the most malaria-associated mortality. Extensive research, especially with the advancement of genomics and transfection tools, has highlighted the fundamental importance of chromatin-mediated gene regulation in the developmental program of this early-branching eukaryote. The Plasmodium parasite genomes reveal the existence of both canonical and variant histones that make up the nucleosomes, as well as a full collection of conserved enzymes for chromatin remodeling and histone posttranslational modifications (PTMs). Recent studies have identified a wide array of both conserved and novel histone PTMs in P. falciparum, indicating the presence of a complex and divergent “histone code.” Genome-wide analysis has begun to decipher the nucleosome landscape and histone modifications associated with the dynamic organization of chromatin structures during the parasite's life cycle. Focused studies on malaria-specific phenomena such as antigenic variation and red cell invasion pathways shed further light on the involvement of epigenetic mechanisms in these processes. Here we review our current understanding of chromatin-mediated gene regulation in malaria parasites, with specific reference to exemplar studies on antigenic variation and host cell invasion.

scholarly journals Penicillinase-Producing Plasmid Types in Neisseria gonorrhoeae Clinical Isolates from Australia

2014 ◽  
Vol 58 (12) ◽  
pp. 7576-7578 ◽  
Author(s):  
David Whiley ◽  
Ella Trembizki ◽  
Cameron Buckley ◽  
Kevin Freeman ◽  
Andrew Lawrence ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Clinical Isolates ◽  
Content Type ◽  
Stepping Stone ◽  
Extended Spectrum

ABSTRACTPenicillinase-producingNeisseria gonorrhoeae(PPNG) carrying theblaTEM-135gene is of particular concern, as it is considered a stepping stone toward resistance to extended-spectrum cephalosporins. Here, we sought to characterize plasmid types and the occurrence of theblaTEM-135gene forN. gonorrhoeaeclinical isolates from Australia. We found thatblaTEM-135was prevalent in Australian PPNG and was detected on all three major plasmid types.

Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures

1983 ◽  
Vol 58 (2) ◽  
pp. 236-241 ◽  
Author(s):  
Byron Young ◽  
Robert P. Rapp ◽  
J. A. Norton ◽  
Dennis Haack ◽  
Phillip A. Tibbs ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Public Health Problem ◽  
Controlled Study ◽  
Major Public Health Problem ◽  
Blood Concentrations ◽  
Content Type ◽  
Posttraumatic Epilepsy ◽  
Significant Difference ◽  
Posttraumatic Seizures ◽  
Fine Print

✓ This randomized double-blind placebo-controlled study was undertaken in a series of 179 patients to determine whether phenytoin administered soon after head injury lessens the incidence of late posttraumatic epilepsy. When delayed hypersensitivity to phenytoin developed, the patient was switched to phenobarbital. The patients were followed for 18 months to detect the occurrence of seizures and to serially measure plasma phenytoin concentrations. There was no significant difference in the percentage of patients having late seizures in the treated and placebo groups (p = 0.75). The time between injury and seizures did not significantly differ between the two groups. The results provide no support for the continued use of phenytoin in the low therapeutic range for prophylaxis against late posttraumatic seizures. It cannot be concluded that higher phenytoin plasma concentrations and higher compliance rates than obtained in this study would not have significantly decreased the occurrence of late posttraumatic epilepsy. The finding that no patient with a phenytoin plasma concentration of 12 µg/ml or higher had a seizure raises the question of whether phenytoin in blood concentrations in higher therapeutic ranges might lessen the occurrence of posttraumatic epilepsy, and should be studied further. Posttraumatic epilepsy is a major public health problem deserving a large cooperative trial to determine if phenytoin at higher blood levels than obtained in this study, or other currently available or newly developed drugs, can prevent the occurrence of posttraumatic epilepsy.

Prevalence of porA pseudogene deletion among Neisseria gonorrhoeae isolates referred to the UK’s Gonococcal Resistance to Antimicrobials Surveillance Program

Sexual Health ◽  
2017 ◽  
Vol 14 (4) ◽  
pp. 392 ◽  
Author(s):  
Martina Toby ◽  
Pamela Saunders ◽  
Michelle Cole ◽  
Vlad Grigorjev ◽  
Sarah Alexander ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
False Negative ◽  
Public Health Problem ◽  
Surveillance Program ◽  
Major Public Health Problem ◽  
Negative Results ◽  
False Negative Results ◽  
Confirmatory Tests ◽  
Polymerase Chain ◽  
Low Prevalence

porA pseudogene-negative Neisseria gonorrhoeae isolates produce false-negative results when examined by polymerase chain reaction (PCR) with porA pseudogene targets. In the present study, 533 representative gonococcal isolates received in 2011 via the Gonococcal Resistance to Antimicrobials Surveillance Program were examined to determine the prevalence of porA-negative isolates. Less than 0.4% (2/533) of isolates were found to be reproducibly negative with the porA real-time PCR but were confirmed as N. gonorrhoeae with molecular, biochemical and immunological confirmatory tests. Sequencing revealed both isolates contained the Neisseria meningitidis porA gene. Low prevalence indicates that although these isolates do not present a major public health problem, microbiologists should remain vigilant.

scholarly journals Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China (2014-2018)

2020 ◽  
Author(s):  
Wenjing Le ◽  
Xiaohong Su ◽  
Xiangdi Lou ◽  
Xuechun Li ◽  
Xiangdong Gong ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Dna Sequencing ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Extended Spectrum ◽  
High Level ◽  
Level Resistance

ABSTRACTPreviously, we reported potent activity of a novel spiropyrimidinetrione, zoliflodacin, against N. gonorrhoeae isolates from symptomatic men in Nanjing, China, collected in 2013. Here, we investigated trends of susceptibilities of zoliflodacin in 986 gonococcal isolates collected from men between 2014 and 2018. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in gyrA, gyrB, parC and parE genes were determined by PCR and DNA sequencing. The MIC of zoliflodacin for N. gonorrhoeae ranged from ≤0.002 to 0.25 mg/L; the overall MIC50s and MIC90s were 0.06 mg/L and 0.125mg/L in 2018, increasing two-fold from 2014. However, the percent of isolates with lower zoliflodacin MICs declined in each year sequentially while the percent with higher MICs increased yearly (P≤0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥1 μg/ml); 21.2% (209/986) were resistant to azithromycin (≥1 μg/ml), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) tetracycline-resistant (TRNG) and 19.4% (191/986) were multi-drug resistant (MDR) isolates. Among 143 isolates with higher zoliflodacin MICs (0.125-0.25 mg/L), all had quinolone resistance associated double or triple mutations in gyrA; 139/143 (97.2%) also had mutations in parC. There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; a S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin has excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin and extended spectrum cephalosporins.

scholarly journals Enhancing the natural toxicity of Salmonella Typhimurium towards tumours

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Najla Alfaqeer ◽  
Donal Wall
Keyword(s):  
Food Poisoning ◽  
Public Health Problem ◽  
Effector Proteins ◽  
Major Public Health Problem ◽  
Wild Type ◽  
Level Of Invasion ◽  
Mutant Strains ◽  
High Level ◽  
Initial Results ◽  
Number Of Bacteria

Background and objective: Salmonella is the underlying cause of foodborne diseases and poses a major public health problem worldwide. Research has developed a method to efficiently treat cancer using some of the same bacteria behind food poisoning, one of these bacteria is Salmonella which targets and penetrats tumours specifically by being attracted to the compounds produced by tumour cells and accumulating at the tumour site and inducing inflammation. In this project we aim to investigate the mechanism of Salmonella Typhimurium which has a tremendous ability to invade, replicate and compete to survive inside the cells by virtue of effector proteins such as: sipA, sipB, and AvrA which it possesses. Method: The S.Typhimurium strains used are wild-type SL1344 ( ΔsipA, ΔsipB, ΔavrA and VV341) and attenuated strain of SL7207. Bacteria were cultured in LB broth in a 37 °C shaker overnight to reach a stationary phase before using it to infect B16F10 (mouse melanoma). Results: The initial results show that the infection of B16F10 with wild-type SL1344 had a high level of invasion compared to the low number of bacteria with the deletion of sipB which impaired its entry into the cell. Similarly, the mutant strains ΔsipA and ΔavrA show an increasing number of intracellular bacteria, like the wild-type strain. We will be investigating further on the innate mechanisms of Salmonella in disrupting tumour growth and progression, that might help maximize the potential of using these bacteria in monotherapy or in tandem with other useful therapies.

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