Canary in the Coal Mine: How Resistance Surveillance in Commensals Could Help Curb the Spread of AMR in Pathogenic
            <i>Neisseria</i>

Goytia, Maïra; Wadsworth, Crista B.

doi:10.1128/mbio.01991-22

Cited by 21 publications

(28 citation statements)

References 164 publications

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“…Moreover, colistin is never used in clinical treatment of Shigella or Salmonella , so the presence of this gene is less worrisome. Even so, the presence of the mcr-9 genes is still relevant for their potential spread to other pathogens that are treated with colistin [ 81 ].…”

Section: Resultsmentioning

confidence: 99%

Using a combination of short- and long-read sequencing to investigate the diversity in plasmid- and chromosomally encoded extended-spectrum beta-lactamases (ESBLs) in clinical Shigella and Salmonella isolates in Belgium

et al. 2023

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For antimicrobial resistance (AMR) surveillance, it is important not only to detect AMR genes, but also to determine their plasmidic or chromosomal location, as this will impact their spread differently. Whole-genome sequencing (WGS) is increasingly used for AMR surveillance. However, determining the genetic context of AMR genes using only short-read sequencing is complicated. The combination with long-read sequencing offers a potential solution, as it allows hybrid assemblies. Nevertheless, its use in surveillance has so far been limited. This study aimed to demonstrate its added value for AMR surveillance based on a case study of extended-spectrum beta-lactamases (ESBLs). ESBL genes have been reported to occur also on plasmids. To gain insight into the diversity and genetic context of ESBL genes detected in clinical isolates received by the Belgian National Reference Center between 2013 and 2018, 100 ESBL-producing Shigella and 31 ESBL-producing Salmonella were sequenced with MiSeq and a representative selection of 20 Shigella and six Salmonella isolates additionally with MinION technology, allowing hybrid assembly. The bla CTX-M-15 gene was found to be responsible for a rapid rise in the ESBL Shigella phenotype from 2017. This gene was mostly detected on multi-resistance-carrying IncFII plasmids. Based on clustering, these plasmids were determined to be distinct from the circulating plasmids before 2017. They were spread to different Shigella species and within Shigella sonnei between multiple genotypes. Another similar IncFII plasmid was detected after 2017 containing bla CTX-M-27 for which only clonal expansion occurred. Matches of up to 99 % to plasmids of various bacterial hosts from all over the world were found, but global alignments indicated that direct or recent ESBL-plasmid transfers did not occur. It is most likely that travellers introduced these in Belgium and subsequently spread them domestically. However, a clear link to a specific country could not be made. Moreover, integration of bla CTX-M in the chromosome of two Shigella isolates was determined for the first time, and shown to be related to ISEcp1. In contrast, in Salmonella , ESBL genes were only found on plasmids, of which bla CTX-M-55 and IncHI2 were the most prevalent, respectively. No matching ESBL plasmids or cassettes were detected between clinical Shigella and Salmonella isolates. The hybrid assembly data allowed us to check the accuracy of plasmid prediction tools. MOB-suite showed the highest accuracy. However, these tools cannot replace the accuracy of long-read and hybrid assemblies. This study illustrates the added value of hybrid assemblies for AMR surveillance and shows that a strategy where even just representative isolates of a collection used for hybrid assemblies could improve international AMR surveillance as it allows plasmid tracking.

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Section: Resultsmentioning

confidence: 99%

Using a combination of short- and long-read sequencing to investigate the diversity in plasmid- and chromosomally encoded extended-spectrum beta-lactamases (ESBLs) in clinical Shigella and Salmonella isolates in Belgium

et al. 2023

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“…Simultaneously, case reports of gonococcal resistance soon began to appear worldwide. 30,31 From a total of 5808 consecutive strains of N. gonorrhoeae were collected for antibiotic MICs evaluation in Guangdong region during 2013-2020, strains with resistance to azithromycin were observed to fluctuate between 8.60% and 20.03%. 32 Between 2014 and 2020, 488 symptomatic gonococcal samples were received from 10 Thai military hospitals, and three samples were determined to be insensitive to azithromycin.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007

Zhang¹,

Hu²,

Huang³

et al. 2023

IDR

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This study aimed to assess the drug susceptibility of clinical isolates of Neisseria gonorrhoeae to spectinomycin, ceftriaxone and azithromycin. Moreover, the temporal trends in the minimum inhibitory concentration (MIC) of five antibiotics from Zhejiang, China, are also in the scope of this study. Methods: A total of 1710 gonococcal clinical strains were collected between 2007 and 2021 from health-care institutions in Zhejiang. The MICs of ceftriaxone, azithromycin, spectinomycin, penicillin and ciprofloxacin were assessed by agar dilution method on 1710 Neisseria gonorrhoeae isolates. Count data were expressed as strains and rates, and MICs distribution was elucidated using descriptive statistics. Results: The total resistance rates of gonococci to azithromycin, spectinomycin, penicillin and ciprofloxacin in this study were 19.3%, 0.3%, 75.4% and 99.7%, respectively. Conclusion:The in vitro results showed a high prevalence of resistance to ciprofloxacin and penicillin. Azithromycin resistance rate has exceeded 5%, suggested a high prevalence of resistance. Ceftriaxone and spectinomycin are suggested based on this study for the treatment of Neisseria gonorrhoeae in Zhejiang.

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“…Commensal Neisseria have repeatedly donated resistance alleles to their pathogenic relative N. gonorrhoeae 28,[35][36][37] , and beyond doubt serve as a bubbling cauldron of new adaptive solutions to address 'the antibiotic crisis' that N. gonorrhoeae faces. However, we do not yet understand the full suite of resistance alleles that commensal Neisseria can carry, if the pool of mechanisms is large or small, and if the pool size varies by antibiotic.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, evolution does not occur in controlled laboratory environments, so what is the role of intergenus gene exchange in Neisseria resistance emergence? Can other genera transfer clinically relevant resistance mechanisms to the Neisseria (see Goytia & Wadsworth (2022) 35 for a discussion on this possibility)? In summary, our current results highlight conserved paths to resistance within the Neisseria genus, though continued tosses of the evolutionary dice may ultimately paint a different picture.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the paths to resistance within gonococci have previously been explored in vitro (e.g., [29][30][31][32][33][34] ). However, gonococci in addition to gaining resistance through de novo mutations, are also superbly adept at acquiring resistance from their close commensal relatives 5,28,[35][36][37] . This allelic exchange across Neisseria species likely occurs in their shared colonization sites of the naso-and oropharyngeal niches 38 , with the whole genus often being referred to as a consortium with 'fuzzy' borders due to the high frequency of DNA donation through horizontal gene transfer (HGT) [39][40][41] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rolling the evolutionary dice:Neisseriacommensals as proxies for elucidating the underpinnings of antibiotic resistance mechanisms and evolution in human pathogens

Frost,

Charron-Smith,

Cotsonas

et al. 2023

Preprint

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Species within the genusNeisseriaare especially adept at sharing adaptive allelic variation across species’ boundaries, with commensal species repeatedly transferring resistance to their pathogenic relativeN. gonorrhoeae. However, resistance in commensalNeisseriais infrequently characterized at both the phenotypic and genotypic levels, limiting our ability to predict novel and potentially transferable resistance mechanisms that ultimately may become important clinically. Unique evolutionary starting places of eachNeisseriaspecies will have distinct genomic backgrounds, which may ultimately control the fate of evolving populations in response to selection, as epistatic and additive interactions may coerce lineages along divergent evolutionary trajectories. However alternatively, similar genetic content present across species due to shared ancestry may constrain the adaptive solutions that exist. Thus, identifying the paths to resistance across commensals may aid in characterizing theNeisseriaresistome – or the reservoir of alleles within the genus, as well as its depth. Here, we usein vitroevolution of four commensal species to investigate the potential for and repeatability of resistance evolution to two antimicrobials, the macrolide azithromycin and the β-lactam penicillin. After 20 days of selection, commensals evolved elevated minimum inhibitory concentrations (MICs) to penicillin and azithromycin in 11/16 and 12/16 cases respectively. Almost all cases of resistance emergence converged on mutations within ribosomal components or themtrRCDEefflux pump for azithromycin-based selection, andmtrRCDEorpenAfor penicillin selection; thus, supporting constrained adaptive solutions despite divergent evolutionary starting points across the genus for these particular drugs. However, continuing to explore the paths to resistance across different experimental conditions and genomic backgrounds, which could shunt evolution down alternative evolutionary trajectories, will ultimately flesh out the fullNeisseriaresistome.

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Canary in the Coal Mine: How Resistance Surveillance in Commensals Could Help Curb the Spread of AMR in Pathogenic Neisseria

Cited by 21 publications

References 164 publications

Using a combination of short- and long-read sequencing to investigate the diversity in plasmid- and chromosomally encoded extended-spectrum beta-lactamases (ESBLs) in clinical Shigella and Salmonella isolates in Belgium

Using a combination of short- and long-read sequencing to investigate the diversity in plasmid- and chromosomally encoded extended-spectrum beta-lactamases (ESBLs) in clinical Shigella and Salmonella isolates in Belgium

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007

Rolling the evolutionary dice:Neisseriacommensals as proxies for elucidating the underpinnings of antibiotic resistance mechanisms and evolution in human pathogens

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