Biology subjects

de Vries, H. J. C.

Publications and source records attributed to de Vries, H. J. C..

3 recordsLinked to original sources

bioRxiv2025

Environmental exposure to antibiotics drives and sustains antibiotic resistance in Neisseria gonorrhoeae: A modelling study

Ciprofloxacin resistance is widespread in Neisseria gonorrhoeae, despite its discontinuation as recommended treatment option in 2007. Unintentional low-level exposure to ciprofloxacin, e.g., environmental or food-borne, might provide sufficiently high selection pressure to maintain resistance and compensate potential fitness costs. We used a mathematical within-host model of gonorrhoea to investigate the effect of low-level ciprofloxacin exposure on susceptibility. We present a mechanistic within-host model of gonococcal infections in the male urethra, to simulate the influence of low-level ciprofloxacin exposures on gonococcal ciprofloxacin susceptibility. We assessed the impact of repeated exposures to varying amounts of ciprofloxacin [Formula] in a chain of sequentially transmitted infections. Daily exposure to at least 0.15mg ciprofloxacin was sufficient to select for low-level resistance. Moreover, in the absence of ciprofloxacin treatment, resistant variants could revert back to variants with lower levels of resistance. However, background exposure can balance fitness costs of resistance and prevent a complete reversion to the fully susceptible variant. Even for human-host restricted pathogens such as Neisseria gonorrhoeae, a One Health approach that considers unintentional antibiotic exposures is needed to avoid the emergence and spread of resistance.

microbiology↗

bioRxiv2020

Emergence of a cephalosporin reduced susceptible Neisseria gonorrhoeae clone between 2014-2019 in Amsterdam, the Netherlands, revealed by a genomic population analysis

BackgroundEmerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of reduced susceptible and resistant strains. AimFor the purpose of epidemiological surveillance, a genomic population analysis was performed on Ng isolates from Amsterdam with a focus on ceftriaxone reduced susceptible isolates. MethodsWhole genome sequences were obtained from 318 isolates from 2014-2019 from Amsterdam, the Netherlands. Isolates were typed according to the Multi-Locus Sequence Typing (MLST) scheme and resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch- and global MLST7827 isolates. ResultsThe majority of ceftriaxone reduced susceptible isolates belonged to MLST7363, MLST1901 and MLST7827. MLST7363 and MLST1901 were dominant reduced susceptible strains from 2014-2016 although MLST7827 emerged and became dominant during 2017-2019. MLST7827 reduced susceptible isolates carried a non-mosaic penA gene with A501V mutation and porB G121K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch- and other European MLST7827 isolates. ConclusionCeftriaxone reduced susceptible MLST7827 isolates emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB G121K/A121D mutations was strongly associated with ceftriaxone reduced susceptibility. Genetic clustering of Dutch- and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Therefore, close monitoring of the spread of this strain with an alarming susceptibility profile is needed.

genomics↗

bioRxiv2017

Pathways-wide genetic risks in Chlamydial infections overlap between tissue tropisms: A genome-wide association scan

Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection and can lead to tubal factor infertility, a disease characterised by fibrosis of the fallopian tubes. Genetic polymorphisms in molecular pathways involving G protein coupled receptor signalling, the Akt/PI3K cascade, the mitotic cell cycle and immune response have been identified in association with the development of trachomatous scarring, an ocular form of chlamydia-related fibrotic pathology. In this case control study, we performed genome-wide association and pathways based analysis in a sample of 71 Dutch women who attended an STI clinic who were seropositive for Chlamydia trachomatis antibodies and 169 high risk Dutch women who sought similar health services but who were seronegative. We identified two regions of within-gene SNP association with Chlamydia trachomatis serological response and found that GPCR signalling and cell cycle pathways were also associated with the trait. These pathway level associations appear to be common to immunological sequelae of Chlamydial infections in both ocular and urogenital tropisms. These pathways may be central mediators of human refractoriness to chlamydial diseases.

genetics↗