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 Exploring Antibiotic Susceptibility, Resistome and Mobilome Structure of Planctomycetes from Gemmataceae Family

2021 ◽  
Vol 13 (9) ◽  
pp. 5031
Author(s):  
Anastasia A. Ivanova ◽  
Kirill K. Miroshnikov ◽  
Igor Y. Oshkin
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Antibiotic Susceptibility ◽  
Large Genome ◽  
Antimicrobial Resistance Genes ◽  
The Family ◽  
Terrestrial Environments ◽  
Environmental Bacteria

The family Gemmataceae accomodates aerobic, chemoorganotrophic planctomycetes with large genome sizes, is mostly distributed in freshwater and terrestrial environments. However, these bacteria have recently also been found in locations relevant to human health. Since the antimicrobial resistance genes (AMR) from environmental resistome have the potential to be transferred to pathogens, it is essential to explore the resistant capabilities of environmental bacteria. In this study, the reconstruction of in silico resistome was performed for all nine available gemmata genomes. Furthermore, the genome of the newly isolated yet-undescribed strain G18 was sequenced and added to all analyses steps. Selected genomes were screened for the presence of mobile genetic elements. The flanking location of mobilizable genomic milieu around the AMR genes was of particular interest since such colocalization may appear to promote the horizontal gene transfer (HGT) events. Moreover the antibiotic susceptibility profile of six phylogenetically distinct strains of Gemmataceae planctomycetes was determined.

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 Natural Horizontal Gene Transfer of Antimicrobial Resistance Genes in Campylobacter spp. From Turkeys and Swine

2021 ◽  
Vol 12 ◽  
Author(s):  
Vanina Guernier-Cambert ◽  
Julian Trachsel ◽  
Joel Maki ◽  
Jing Qi ◽  
Matthew J. Sylte ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Resistance Genes ◽  
Genomic Islands ◽  
Whole Genome ◽  
Antimicrobial Resistance Genes ◽  
Horizontal Spread

Antibiotic-resistant Campylobacter constitutes a serious threat to public health. The clonal expansion of resistant strains and/or the horizontal spread of resistance genes to other strains and species can hinder the clinical effectiveness of antibiotics to treat severe campylobacteriosis. Still, gaps exist in our understanding of the risks of acquisition and spread of antibiotic resistance in Campylobacter. While the in vitro transfer of antimicrobial resistance genes between Campylobacter species via natural transformation has been extensively demonstrated, experimental studies have favored the use of naked DNA to obtain transformants. In this study, we used experimental designs closer to real-world conditions to evaluate the possible transfer of antimicrobial resistance genes between Campylobacter strains of the same or different species (Campylobacter coli or Campylobacter jejuni) and originating from different animal hosts (swine or turkeys). This was evaluated in vitro through co-culture experiments and in vivo with dual-strain inoculation of turkeys, followed by whole genome sequencing of parental and newly emerged strains. In vitro, we observed four independent horizontal gene transfer events leading to the acquisition of resistance to beta-lactams (blaOXA), aminoglycosides [aph(2′′)-If and rpsL] and tetracycline [tet(O)]. Observed events involved the displacement of resistance-associated genes by a mutated version, or the acquisition of genomic islands harboring a resistance determinant by homologous recombination; we did not detect the transfer of resistance-carrying plasmids even though they were present in some strains. In vivo, we recovered a newly emerged strain with dual-resistance pattern and identified the replacement of an existing non-functional tet(O) by a functional tet(O) in the recipient strain. Whole genome comparisons allowed characterization of the events involved in the horizontal spread of resistance genes between Campylobacter following in vitro co-culture and in vivo dual inoculation. Our study also highlights the potential for antimicrobial resistance transfer across Campylobacter species originating from turkeys and swine, which may have implications for farms hosting both species in close proximity.

scholarly journals Antimicrobial susceptibility of commensal Neisseria in a general population and men who have sex with men in Belgium

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Jolein Gyonne Elise Laumen ◽  
Christophe Van Dijck ◽  
Saïd Abdellati ◽  
Irith De Baetselier ◽  
Gabriela Serrano ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
General Population ◽  
Neisseria Gonorrhoeae ◽  
Resistance Genes ◽  
Antimicrobial Susceptibility ◽  
Resistance Determinants ◽  
Antimicrobial Resistance Genes ◽  
Sex With Men ◽  
Commensal Neisseria ◽  
Tof Ms

AbstractNon-pathogenic Neisseria are a reservoir of antimicrobial resistance genes for pathogenic Neisseria meningitidis and Neisseria gonorrhoeae. Men who have sex with men (MSM) are at risk of co-colonization with resistant non-pathogenic and pathogenic Neisseria. We assessed if the antimicrobial susceptibility of non-pathogenic Neisseria among MSM differs from a general population and if antimicrobial exposure impacts susceptibility. We recruited 96 participants at our center in Belgium: 32 employees, 32 MSM who did not use antibiotics in the previous 6 months, and 32 MSM who did. Oropharyngeal Neisseria were cultured and identified with MALDI-TOF–MS. Minimum inhibitory concentrations for azithromycin, ceftriaxone and ciprofloxacin were determined using E-tests® and compared between groups with non-parametric tests. Non-pathogenic Neisseria from employees as well as MSM were remarkably resistant. Those from MSM were significantly less susceptible than employees to azithromycin and ciprofloxacin (p < 0.0001, p < 0.001), but not ceftriaxone (p = 0.3). Susceptibility did not differ significantly according to recent antimicrobial exposure in MSM. Surveilling antimicrobial susceptibility of non-pathogenic Neisseria may be a sensitive way to assess impact of antimicrobial exposure in a population. The high levels of antimicrobial resistance in this survey indicate that novel resistance determinants may be readily available for future transfer from non-pathogenic to pathogenic Neisseria.

scholarly journals Reservoir of Antimicrobial Resistance Determinants Associated with Horizontal Gene Transfer in Clinical Isolates of the Genus Shewanella

2010 ◽  
Vol 54 (10) ◽  
pp. 4516-4517 ◽  
Author(s):  
María Soledad Ramírez ◽  
Marisa Almuzara ◽  
Daniela Centrón ◽  
Andrea Karina Merkier ◽  
Carlos Vay
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Clinical Isolates ◽  
Resistance Determinants

scholarly journals Hortense: Horizontal gene transfer detection directly from proteomic MS/MS data

2017 ◽  
Author(s):  
Kathrin Trappe ◽  
Ben Wulf ◽  
Joerg Doellinger ◽  
Sven Halbedel ◽  
Thilo Muth ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Large Scale ◽  
Genomic Sequence ◽  
Simulated Data ◽  
Negative Control ◽  
Detection Methods ◽  
Resistant Bacteria ◽  
Antimicrobial Resistance Genes

Horizontal gene transfer (HGT) is a powerful mechanism that allows bacteria to directly transfer long stretches of genomic sequence from one individual to another. The transfer of antimicrobial resistance genes is a prominent example of HGT events in the context of multi-resistant bacteria which pose a high risk to human health. While several approaches for HGT detection exist on the genomic level, to the best of our knowledge, HGT events have not been investigated in a detailed mass spectrometry (MS)-based proteomic study. However, the mere presence of a gene does not necessarily correlate with its expression at the protein level. Consequently, to draw conclusions with respect to the expression of HGT-mediated genes, MS-based proteomics can be employed. We developed a first computational approach - called Hortense - for automated HGT detection directly from shotgun proteomics experiments. We extend the standard database search by a critical cross-validation to unravel potential HGT proteins. A proteogenomic extension gives information about the genomic origin and enables an integration with existing genome-based methods. We successfully validated our approach on simulated data, and further evaluated it on real data from a transgenic organism and a negative control from an organism not harboring a transferred gene. Our results indicate that our method facilitates MS-based analysis for proteomic evidence of HGT events. Especially as an orthogonal approach to genome-based HGT detection methods, our proposed workflow is a first step toward a systematic and large scale analysis of HGT events in, e.g., antimicrobial resistance context. Hortense is publicly available at https://gitlab.com/rki_bioinformatics/.

scholarly journals Simulated Microgravity Promotes Horizontal Gene Transfer of Antimicrobial Resistance Genes between Bacterial Genera in the Absence of Antibiotic Selective Pressure

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 960
Author(s):  
Camilla Urbaniak ◽  
Tristan Grams ◽  
Christopher E. Mason ◽  
Kasthuri Venkateswaran
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Bacterial Communities ◽  
Simulated Microgravity ◽  
Space Environment ◽  
Phenotypic Change ◽  
Long Duration ◽  
Antimicrobial Resistance Genes ◽  
Acinetobacter Pittii

Bacteria are able to adapt and survive in harsh and changing environments through many mechanisms, with one of them being horizontal gene transfer (HGT). This process is one of the leading culprits in the spread of antimicrobial resistance (AMR) within bacterial communities and could pose a significant health threat to astronauts if they fell ill, especially on long-duration space missions. In order to better understand the degree of HGT activity that could occur in space, biosafety level-2, donor and recipient bacteria were co-cultured under simulated microgravity (SMG) on Earth with concomitant 1G controls. Two AMR genes, blaOXA-500 and ISAba1, from the donor Acinetobacter pittii, were tracked in four recipient strains of Staphylococcus aureus (which did not harbor those genes) using polymerase chain reaction. All four S. aureus strains that were co-cultured with A. pittii under SMG had a significantly higher number of isolates that were now blaOXA-500- and ISAba1-positive compared to growth at 1G. The acquisition of these genes by the recipient induced a phenotypic change, as these isolates were now resistant to oxacillin, which they were previously susceptible to. This is a novel study, presenting, for the first time, increased HGT activity under SMG and the potential impact of the space environment in promoting increased gene dissemination within bacterial communities.

The mosaic mtr locus as major genetic determinant of azithromycin resistance of Neisseria gonorrhoeae, Germany, 2018

2021 ◽  
Author(s):  
Sebastian Banhart ◽  
Regina Selb ◽  
Sandra Oehlmann ◽  
Jennifer Bender ◽  
Susanne Buder ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Neisseria Gonorrhoeae ◽  
Genome Sequencing ◽  
Point Mutations ◽  
Whole Genome ◽  
Genetic Determinant ◽  
Sample Collection ◽  
Resistance Determinants ◽  
Azithromycin Resistance

Abstract Within the German Gonococcal Resistance Network (GORENET) Neisseria gonorrhoeae (NG) sample collection, azithromycin-resistant NG isolates increased from 4.3% in 2016 to 9.2% in 2018. We aim to understand this observed increase using whole genome sequencing of NG isolates combined with epidemiological and clinical data. Reduced susceptibility to azithromycin in 2018 was predominately clonal (NG-MAST G12302) and could mainly be accounted to the recently described mosaic-like mtr locus. Our data suggest that, together with horizontal gene transfer of resistance determinants and well-established point mutations, international spread of resistant lineages plays a major role regarding azithromycin resistance in Germany.

scholarly journals Horizontal Gene Transfer Is the Main Driver of Antimicrobial Resistance in Broiler Chicks Infected with Salmonella enterica Serovar Heidelberg

mSystems ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Adelumola Oladeinde ◽  
Zaid Abdo ◽  
Maximilian O. Press ◽  
Kimberly Cook ◽  
Nelson A. Cox ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Antibiotic Use ◽  
Resistant Bacteria ◽  
Broiler Chicks ◽  
Antibiotic Resistant ◽  
Food Animal ◽  
Main Driver ◽  
Major Shift

The reported increase in antibiotic-resistant bacteria in humans has resulted in a major shift away from antibiotic use in food animal production. This shift has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, which in turn will allow the currently available antibiotic arsenal to be more effective.

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