Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates

Balduck, Margaux; Laumen, Jolein; Abdellati, Saïd; Baetselier, Irith De; Block, Tessa de; Manoharan-Basil, Sheeba Santhini; Kenyon, Chris

doi:10.3390/antibiotics11111480

Cited by 8 publications

(20 citation statements)

References 45 publications

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“…Previously, we reported that tolerance to CRO can be induced in CRO-susceptible (<0.004 µg/mL) N. gonorrhoeae WHO P reference isolate [ 17 ]. In the current analysis, we describe, for the first time, the mutations associated with emergence of CRO tolerance in N. gonorrhoeae.…”

Section: Discussionmentioning

confidence: 99%

“…We recently induced tolerance to ceftriaxone (CRO) in N. gonorrhoeae reference isolates (WHO P) [ 17 ]. A highly susceptible CRO reference strain, WHO P with a CRO MIC of 0.004 µg/mL, was used [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…Blue arrow indicates emergent tolerant colonies at Step III. Figure is reproduced with permission from [ 17 ].…”

Section: Figurementioning

confidence: 99%

“…We recently succeeded in inducing tolerance to ceftriaxone (CRO) via intermittent cyclic CRO exposure in N. gonorrhoeae reference isolates (WHO P) [ 17 ]. In the current study, using whole-genome sequencing (WGS), we characterized the mutation profile of these CRO-tolerant phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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Enolase Is Implicated in the Emergence of Gonococcal Tolerance to Ceftriaxone

et al. 2023

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Antibiotic tolerance is associated with antibiotic treatment failure, and molecular mechanisms underlying tolerance are poorly understood. We recently succeeded in inducing tolerance to ceftriaxone (CRO) in an N. gonorrhoeae reference isolate. In a prior in vitro study, six biological replicates of WHO P strains were exposed to CRO (10× the MIC) followed by overnight growth, and tolerance was assessed using a modified Tolerance Disc (T.D.) test. In the current study, we characterized the mutation profile of these CRO-tolerant phenotypes. The whole genome was sequenced from isolates from different replicates and time points. We identified mutations in four genes that may contribute to ceftriaxone tolerance in N. gonorrhoeae, including a mutation in the enolase (eno) gene that arose independently in three lineages.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Blue arrow indicates emergent tolerant colonies at Step III. Figure is reproduced with permission from [ 17 ].…”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enolase Is Implicated in the Emergence of Gonococcal Tolerance to Ceftriaxone

et al. 2023

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“… 11 In addition, tolerance to ceftriaxone was found in clinical samples. 12 However, if the surveillance data cannot interpret the current situation of gonorrhea epidemic, misleading may be inevitable in policy making for gonorrhea prevention and control. Many factors may affect the integrity and accuracy of surveillance data.…”

Section: Introductionmentioning

confidence: 99%

Availability of Laboratory Diagnosis of Gonorrhoea and Its Meaning in Case Reporting in Shandong Province, China

Chen

Gan

Liu

2023

CCID

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Background Gonorrhea, caused by the bacterium Neisseria gonorrhoeae (NG), is a major public health concern worldwide. Aim of the Study The aim of this study is to understand the availability of laboratory diagnosis of gonorrhoea in Shandong province and its meaning in case reporting. Methods Two surveys were conducted among hospitals providing clinical services for sexually transmitted infection (STI) in Shandong Province in 2012 and 2018. The availability of laboratory tests for NG and distribution of reported gonorrhea cases were compared among different hospitals provided clinical services for STI in Shandong province. Descriptive analysis and Chi-square were used for statistical analysis. Results Smear, culture and PCR tests for NG were used among 301(74.69%), 123(30.52%), 43(10.67%) hospitals in 2012 and 356(74.48%), 176(36.82%) and 73(15.27%) hospitals in 2018, respectively. Significant differences were observed in the availability of smear among hospitals at different levels (X 2 =12.159, p=0.000) and with different affiliations (X 2 =4.551, p=0.033) in 2018. Significant differences were observed in the availability of culture and PCR tests among hospitals at different levels both in 2012 (X 2 =34.532, p=0.000; X 2 =7.380, p=0.007) and 2018 (X 2 =49.820, p=0.000; X 2 =21.658, p=0.000). The availability of culture and PCR tests for NG among hospitals in 2018 was higher than that in 2012 (X 2 =3.870, p=0.049; X 2 =4.050, p=0.044). More hospitals reported gonorrhea cases in 2018 than in 2012 (X 2 =6.768, p=0.009). A significant difference was observed in distribution of case reporting among hospitals at different levels in 2018 (X 2 =6.975, p=0.008) and among different types of hospital both in 2012 (X 2 =52.362, p=0.000) and 2018 (X 2 =74.478, p=0.000). Conclusion Poor availability of NG laboratory tests affects case reporting, and which is a crucial reason leading to underreporting of gonorrhea cases in Shandong province.

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Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance

Deventer,

Stevens,

Stewart

et al. 2024

Clin Microbiol Rev

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SUMMARY Antibiotic treatment failures in the absence of resistance are not uncommon. Recently, attention has grown around the phenomenon of antibiotic tolerance, an underappreciated contributor to recalcitrant infections first detected in the 1970s. Tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic without exhibiting resistance. With advances in genomics, we are gaining a better understanding of the molecular mechanisms behind tolerance, and several studies have sought to examine the clinical prevalence of tolerance. Attempts have also been made to assess the clinical significance of tolerance through in vivo infection models and prospective/retrospective clinical studies. Here, we review the data available on the molecular mechanisms, detection, prevalence, and clinical significance of genotypic tolerance that span ~50 years. We discuss the need for standardized methodology and interpretation criteria for tolerance detection and the impact that methodological inconsistencies have on our ability to accurately assess the scale of the problem. In terms of the clinical significance of tolerance, studies suggest that tolerance contributes to worse outcomes for patients (e.g., higher mortality, prolonged hospitalization), but historical data from animal models are varied. Furthermore, we lack the necessary information to effectively treat tolerant infections. Overall, while the tolerance field is gaining much-needed traction, the underlying clinical significance of tolerance that underpins all tolerance research is still far from clear and requires attention.

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Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates

Cited by 8 publications

References 45 publications

Enolase Is Implicated in the Emergence of Gonococcal Tolerance to Ceftriaxone

Enolase Is Implicated in the Emergence of Gonococcal Tolerance to Ceftriaxone

Availability of Laboratory Diagnosis of Gonorrhoea and Its Meaning in Case Reporting in Shandong Province, China

Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance

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