scholarly journals Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Koji Yahara ◽  
Kevin C. Ma ◽  
Tatum D. Mortimer ◽  
Ken Shimuta ◽  
Shu-ichi Nakayama ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Acquired Resistance ◽  
Antibiotic Use ◽  
Health Concern ◽  
Fluoroquinolone Resistance ◽  
Resistance Mutations ◽  
Treatment Regimens ◽  
Antimicrobial Resistance Genes ◽  
Sequence Types

Abstract Background Antimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to third-generation cephalosporins, mainly due to mosaic penA alleles. These two STs were first detected in Japan; however, the timeline, mechanism, and process of emergence and spread of these mosaic penA alleles to other countries remain unknown. Methods We studied the evolution of penA alleles by obtaining the complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic penA allele 34 (penA-34) dating from 2005 and generating a phylogenetic representation of 1075 strains sampled from 35 countries. We also sequenced the genomes of 103 Japanese ST-7363 N. gonorrhoeae isolates from 1996 to 2005 and reconstructed a phylogeny including 88 previously sequenced genomes. Results Based on an estimate of the time-of-emergence of ST-1901 (harboring mosaic penA-34) and ST-7363 (harboring mosaic penA-10), and > 300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996–2015, we suggest that penA-34 in ST-1901 was generated from penA-10 via recombination with another Neisseria species, followed by recombination with a gonococcal strain harboring wildtype penA-1. Following the acquisition of penA-10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, by independent mutations rather than horizontal gene transfer. Data in the literature suggest that the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time. Conclusions Our findings highlight how antibiotic use and recombination across and within Neisseria species intersect in driving the emergence and spread of drug-resistant gonorrhea.

scholarly journals Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae

2020 ◽  
Author(s):  
Koji Yahara ◽  
Kevin C. Ma ◽  
Tatum D. Mortimer ◽  
Ken Shimuta ◽  
Shu-ichi Nakayama ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Neisseria Gonorrhoeae ◽  
Standard Treatment ◽  
Genetic Resistance ◽  
Antibiotic Use ◽  
First Line ◽  
Resistance Determinants ◽  
Antimicrobial Resistance Genes

AbstractAntimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to treatment with third-generation cephalosporins mainly due to the emergence of mosaic penA alleles. These two STs were first detected in Japan; however, when and how the mosaic penA alleles emerged and spread to other countries remains unknown. Here, we addressed the evolution of penA alleles by obtaining complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic penA allele 34 (penA-34) dating from 2005 and generating a phylogenetic representation of 1,075 strains sampled from 37 countries. We also sequenced the genomes of 103 Japanese ST-7363 N. gonorrhoeae isolates from 1996-2005 and reconstructed a phylogeny including 88 previously sequenced genomes. Based on an estimate of the time of emergence of ST-1901 harboring mosaic penA-34 and ST-7363 harboring mosaic penA-10, and >300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996-2015, we suggest that penA-34 in ST-1901 was generated from penA-10 via recombination with another Neisseria species, followed by a second recombination event with a gonococcal strain harboring wildtype penA-1. Following the acquisition of penA-10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, possibly due to independent mutations rather than horizontal gene transfer. Literature data suggest the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time. Our findings highlight how recombination and antibiotic use across and within Neisseria species intersect in driving the emergence and spread of drug-resistant gonorrhea.Author summaryAntimicrobial resistance is recognized as one of the greatest threats to human health, and Neisseria gonorrhoeae resistance is classified as one of the most urgent. The two major internationally spreading lineages resistant. to first line drugs likely originated in Japan, but when and how their genetic resistance determinants emerged remain unknown. In this study, we conducted an evolutionary analysis using clinical N. gonorrhoeae isolates from 37 countries, including a historical collection of Japanese isolates, to investigate the emergence of resistance in each of the two major lineages. We showed that the penA allele responsible for resistance to cephalosporins, the first-line treatment for gonorrhea, was possibly generated by two recombination events, one from another Neisseria species and one from another N. gonorrhoeae lineage. We also showed that mutations responsible for resistance to a previously widely used antibiotic treatment occurred twice independently in one of the two major lineages. The emergence of the genetic resistance determinants potentially reflects selection from the standard treatment regimen at that time. Our findings highlight how recombination (horizontal gene transfer) and antibiotic use across and within a bacterial species intersect in driving the emergence and spread of antimicrobial resistance genes and mutations.

scholarly journals Changing Antimicrobial Resistance Profiles among Neisseria gonorrhoeae Isolates in Italy, 2003 to 2012

2014 ◽  
Vol 58 (10) ◽  
pp. 5871-5876 ◽  
Author(s):  
Anna Carannante ◽  
Giovanna Renna ◽  
Ivano Dal Conte ◽  
Valeria Ghisetti ◽  
Alberto Matteelli ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Health Concern ◽  
Content Type ◽  
Resistance Patterns ◽  
Sex With Men ◽  
Sequence Types

ABSTRACTThe emergence ofNeisseria gonorrhoeaeisolates displaying resistance to antimicrobial agents is a major public health concern and a serious issue related to the occurrence of further untreatable gonorrhea infections. A retrospective analysis on 1,430N. gonorrhoeaeisolates, collected from 2003 through 2012, for antimicrobial susceptibility by Etest and molecular characterization byNeisseria gonorrhoeaemultiantigen sequence typing (NG-MAST) was carried out in Italy. Azithromycin-resistant gonococci decreased from 14% in 2007 to 2.2% in 2012. Similarly, isolates with high MICs to cefixime (>0.125 mg/liter) decreased from 11% in 2008 to 3.3% in 2012. The ciprofloxacin resistance rate remains quite stable, following an increasing trend up to 64% in 2012. The percentage of penicillinase-producingN. gonorrhoeae(PPNG) significantly declined from 77% in 2003 to 7% in 2012. A total of 81 multidrug-resistant (MDR) gonococci were identified, showing 11 different antimicrobial resistance patterns. These were isolated from men who have sex with men (MSM) and from heterosexual patients. Two sequence types (STs), ST661 and ST1407, were the most common. Genogroup 1407, which included cefixime-, ciprofloxacin-, and azithromycin-resistant isolates, was found. In conclusion, a change in the antimicrobial resistance profiles among gonococci was identified in Italy together with a percentage of MDR isolates.

scholarly journals Genotypic Characterization of Antimicrobial Resistant Salmonella spp. Strains from Three Poultry Processing Plants in Colombia

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 491
Author(s):  
Alejandra Ramirez-Hernandez ◽  
Ana K. Carrascal-Camacho ◽  
Andrea Varón-García ◽  
Mindy M. Brashears ◽  
Marcos X. Sanchez-Plata
Keyword(s):  
Antimicrobial Resistance ◽  
Salmonella Spp ◽  
Microbial Profile ◽  
Antimicrobial Resistance Genes ◽  
Processing Plants ◽  
Poultry Processing ◽  
Paratyphi B ◽  
And Control ◽  
Sequence Types

The poultry industry in Colombia has implemented several changes and measures in chicken processing to improve sanitary operations and control pathogens’ prevalence. However, there is no official in-plant microbial profile reference data currently available throughout the processing value chains. Hence, this research aimed to study the microbial profiles and the antimicrobial resistance of Salmonella isolates in three plants. In total, 300 samples were collected in seven processing sites. Prevalence of Salmonella spp. and levels of Enterobacteriaceae were assessed. Additionally, whole-genome sequencing was conducted to characterize the isolated strains genotypically. Overall, the prevalence of Salmonella spp. in each establishment was 77%, 58% and 80% for plant A, B, and C. The mean levels of Enterobacteriaceae in the chicken rinsates were 5.03, 5.74, and 6.41 log CFU/mL for plant A, B, and C. Significant reductions were identified in the counts of post-chilling rinsate samples; however, increased levels were found in chicken parts. There were six distinct Salmonella spp. clusters with the predominant sequence types ST32 and ST28. The serotypes Infantis (54%) and Paratyphi B (25%) were the most commonly identified within the processing plants with a high abundance of antimicrobial resistance genes.

scholarly journals Unsafe “crossover-use” of chloramphenicol in Uganda: importance of a One Health approach in antimicrobial resistance policy and regulatory action

2021 ◽  
Author(s):  
Kayley D. McCubbin ◽  
John W. Ramatowski ◽  
Esther Buregyeya ◽  
Eleanor Hutchinson ◽  
Harparkash Kaur ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Focus Group ◽  
Low Income ◽  
One Health ◽  
Antibiotic Use ◽  
Regulatory Action ◽  
Health Concern ◽  
Drug Shop ◽  
Human Consumption ◽  
Human Use

AbstractSince the introduction of antibiotics into mainstream health care, resistance to these drugs has become a widespread issue that continues to increase worldwide. Policy decisions to mitigate the development of antimicrobial resistance are hampered by the current lack of surveillance data on antibiotic product availability and use in low-income countries. This study collected data on the antibiotics stocked in human (42) and veterinary (21) drug shops in five sub-counties in Luwero district of Uganda. Focus group discussions with drug shop vendors were also employed to explore antibiotic use practices in the community. Focus group participants reported that farmers used human-intended antibiotics for their livestock, and community members obtain animal-intended antibiotics for their own personal human use. Specifically, chloramphenicol products licensed for human use were being administered to Ugandan poultry. Human consumption of chloramphenicol residues through local animal products represents a serious public health concern. By limiting the health sector scope of antimicrobial resistance research to either human or animal antibiotic use, results can falsely inform policy and intervention strategies. Therefore, a One Health approach is required to understand the wider impact of community antibiotic use and improve overall effectiveness of intervention policy and regulatory action.

Antimicrobial resistance mechanisms, MLST and NG-STAR sequence types of diverse Neisseria gonorrhoeae isolates in KwaZulu-Natal, South Africa

2021 ◽  
Author(s):  
Nireshni Mitchev ◽  
Ravesh Singh ◽  
Mushal Allam ◽  
Stanford Kwenda ◽  
Arshad Ismail ◽  
...  
Keyword(s):  
South Africa ◽  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Point Mutations ◽  
Resistance Mechanisms ◽  
Public Healthcare ◽  
Multiple Sequence ◽  
Genotypic Analysis ◽  
Kwazulu Natal ◽  
Sequence Types

Objective: Antimicrobial resistance (AMR) is a major challenge to managing infectious diseases. Africa has the highest incidence of gonorrhoea but there is a lack of comprehensive data from sparse surveillance programs. This study investigated the molecular epidemiology and AMR profiles of Neisseria gonorrhoeae isolates in KwaZulu-Natal province (KZN), South Africa. Methods: Repository isolates, from patients attending public healthcare clinics for STI care, were used for phenotypic and genotypic analysis. Etest® was performed to determine antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to determine epidemiology and to predict susceptibility by detecting resistance-associated genes and mutations. Results: Among the 61 isolates, multiple sequence types were identified. Six isolates were novel as determined by multilocus sequence typing. N.gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) determined 48 sequence types, of which 35 isolates had novel antimicrobial profiles. Two novel penA alleles and eight novel mtrR alleles were identified. Point mutations were detected in gyrA , parC , mtrR , penA , ponA and porB1 . This study revealed a high prevalence of AMR (penicillin 67%, tetracycline 89% and ciprofloxacin 52%). However, spectinomycin, cefixime, ceftriaxone and azithromycin remained 100% effective. Conclusion: This study is one of the first to comprehensively describe the epidemiology and AMR of N. gonorrhoeae in KZN, South Africa and Africa, using WGS. KZN has a wide strain diversity and most of these sequence types have been detected in multiple countries, however more than half of our isolates have novel antimicrobial profiles. Continued surveillance is crucial to monitor the emergence of resistance to cefixime, ceftriaxone and azithromycin.

scholarly journals Differences in Neisseria gonorrhoeae population structure and antimicrobial resistance pattern between men who have sex with men and heterosexuals

2016 ◽  
Vol 145 (2) ◽  
pp. 379-385 ◽  
Author(s):  
J. SERRA-PLADEVALL ◽  
M. J. BARBERÁ ◽  
A. E. CALLARISA ◽  
R. BARTOLOMÉ-COMAS ◽  
A. ANDREU
Keyword(s):  
Population Structure ◽  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Antimicrobial Susceptibility ◽  
Sexual Practices ◽  
Resistance Pattern ◽  
High Prevalence ◽  
Sex With Men ◽  
Resistance Rates ◽  
Sequence Types

SUMMARYThis study compared the antimicrobial susceptibility and genotypes of strains of Neisseria gonorrhoeae isolated from men who have sex with men (MSM) and from heterosexuals. One hundred and eleven strains were characterized from 107 patients, comprising 57 strains from 54 heterosexuals and 54 strains from 53 MSM. Antimicrobial resistance rates were higher in strains from heterosexual patients, with resistance to cefixime (P = 0·0159) and ciprofloxacin (P = 0·002) being significantly higher. Typing by N. gonorrhoeae multi-antigen sequence typing (NG-MAST) showed that the most prevalent sequence types (ST) and genogroups (G) respectively were ST2400, ST2992, and ST5793, and G1407, G2992, and G2400. A statistically significant association was observed for MSM and genogroups G2400 (P = 0·0005) and G2992 (P = 0·0488), and G1407 with heterosexuals (P = 0·0002). We conclude that in our region distinct populations of gonococci are circulating among subjects with different sexual practices, with their corresponding transmission patterns. Furthermore, the high prevalence of genotype G2400 in MSM, has not to our knowledge been previously described.

Emergence of mgrB locus deletion mediating polymyxin resistance in pandemic KPC-producing Klebsiella pneumoniae ST15 lineage

2021 ◽  
Author(s):  
Luís Guilherme de Araújo Longo ◽  
Herrison Fontana ◽  
Viviane Santos de Sousa ◽  
Natalia Chilinque Zambão da Silva ◽  
Ianick Souto Martins ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Type Species ◽  
Virulence Genes ◽  
Health Concern ◽  
Beta Lactamase ◽  
Content Type ◽  
Link Type ◽  
Antimicrobial Resistance Genes ◽  
Encoding Gene

Klebsiella pneumoniae causes a diversity of infections in both healthcare and community settings. This pathogen is showing an increased ability to accumulate antimicrobial resistance and virulence genes, making it a public health concern. Here we describe the whole-genome sequence characteristics of an ST15 colistin-resistant K. pneumoniae isolate obtained from a blood culture of a 79-year-old female patient admitted to a university hospital in Brazil. Kp14U04 was resistant to most clinically useful antimicrobial agents, remaining susceptible only to aminoglycosides and fosfomycin. The colistin resistance in this isolate was due to a ~1.3 kb deletion containing four genes, namely mgrB, yebO, yobH and the transcriptional regulator kdgR. The study isolate presented a variety of antimicrobial resistance genes, including the carbapenemase-encoding gene bla KPC-2, the extended-spectrum beta-lactamase (ESBL)-encoding gene bla SHV-28 and the beta-lactamase-encoding gene bla OXA-1. Additionally, Kp14U04 harboured a multiple stress resistance protein, efflux systems and regulators, heavy metal resistance and virulence genes, plasmids, prophage-related sequences and genomic islands. These features revealed the high potential of this isolate to resist antimicrobial therapy, survive in adverse environments, cause infections and overcome host defence mechanisms.

Virulence and antimicrobial resistance genes associated with the in-vivo pathogenicity of avian pathogenic E. coli isolates

2021 ◽  
Vol 1 (1) ◽  
pp. 17-20
Author(s):  
Ahmed Abd El-Mawgoud ◽  
Azza El-Sawah ◽  
Soad Nasef ◽  
Al-Hussien Dahshan ◽  
Ahmed Ali
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Broiler Chickens ◽  
Virulence Genes ◽  
Virulence Gene ◽  
Health Concern ◽  
Pathogenicity Test ◽  
E Coli ◽  
Antimicrobial Resistance Genes

In the current study, ten avian pathogenic E. coli (APEC) isolates of the most predominant APEC serogroups isolated from broiler chickens in Egypt were screened for their virulence and antimicrobial resistance genes pattern using PCR. Five selected virulence gene patterns were further investigated for their in-vivo pathogenicity test. Results showed a 100% prevalence of the β-lactams and tetracyclines resistance genes. However, aminoglycoside and quinolone resistance genes were not detected. Also, 80% of the tested isolates harbored mcr-1 gene, colistin resistance gene. In-vivo pathogenic strains consistently harbored the virulence gene pattern of fimH, fimA, papC, iutA, and tsh. Additionally, the tsh gene was consistently detected with lethal APEC isolates in day-old chicks. These results highlighted the high prevalence of antimicrobial and virulence genes in APEC that potentially represent a public health concern. In this study, the virulence genes fimH, fimA, papC, iutA, and tsh were the most common virulence gene patterns associated with pathogenicity in day-old chicks.

scholarly journals Isoniazid and Rifampin-Resistance Mutations Associated With Resistance to Second-Line Drugs and With Sputum Culture Conversion

2020 ◽  
Vol 221 (12) ◽  
pp. 2072-2082 ◽  
Author(s):  
Eleanor S Click ◽  
Ekaterina V Kurbatova ◽  
Heather Alexander ◽  
Tracy L Dalton ◽  
Michael P Chen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Acquired Resistance ◽  
Sputum Culture ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Bivariate Analysis ◽  
Molecular Testing ◽  
Resistance Mutations ◽  
Sputum Culture Conversion ◽  
Culture Conversion

Abstract Background Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. Methods In a multicountry prospective cohort study of multidrug-resistant TB, we identified inhA, katG, and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time to sputum culture conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. Results In total, 447 participants enrolled from January 2005 to December 2008 from 7 countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance. Relative to mutation of katG only, mutation of inhA promoter and katG was associated with baseline extensively drug resistant (XDR) TB, increased acquired fluoroquinolone resistance, and slower TSCC (125.5 vs 89.0 days). Conclusions Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile.

scholarly journals Knowledge, Attitudes and Practices of Veterinarians Towards Antimicrobial Resistance and Stewardship in Nigeria

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 453
Author(s):  
Usman O. Adekanye ◽  
Abel B. Ekiri ◽  
Erika Galipó ◽  
Abubakar Bala Muhammad ◽  
Ana Mateus ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Stewardship ◽  
Online Survey ◽  
Action Plan ◽  
Prophylactic Antibiotic ◽  
Antibiotic Use ◽  
Health Concern ◽  
Attitudes And Practices ◽  
Laboratory Services ◽  
Knowledge Attitudes And Practices

Antimicrobial resistance (AMR) is a global health concern and the inappropriate use of antibiotics in animals and humans is considered a contributing factor. A cross-sectional survey to assess the knowledge, attitudes and practices of veterinarians regarding AMR and antimicrobial stewardship was conducted in Nigeria. A total of 241 respondents completed an online survey. Only 21% of respondents correctly defined the term antimicrobial stewardship and 59.8% were unaware of the guidelines provided by the Nigeria AMR National Action Plan. Over half (51%) of the respondents indicated that prophylactic antibiotic use was appropriate when farm biosecurity was poor. Only 20% of the respondents conducted antimicrobial susceptibility testing (AST) frequently, and the unavailability of veterinary laboratory services (82%) and the owner’s inability to pay (72%) were reported as key barriers to conducting AST. The study findings suggest strategies focusing on the following areas may be useful in improving appropriate antibiotic use and antimicrobial stewardship among veterinarians in Nigeria: increased awareness of responsible antimicrobial use among practicing and newly graduated veterinarians, increased dissemination of regularly updated antibiotic use guidelines, increased understanding of the role of good biosecurity and vaccination practices in disease prevention, and increased provision of laboratory services and AST at affordable costs.

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