Orsolya Dobay

Background/Objectives: Stereochemistry can substantially influence the biological activity and pharmaceutical properties of small molecules. This study investigated the stereochemistry-dependent biological activity and chiral recognition of novel naphthylethyl thiourea enantiomers using an integrated biological, chromatographic, and computational approach. Methods: Ten pairs of naphthylethyl thiourea enantiomers were synthesized from enantiomerically pure precursors and characterized. Antiproliferative and antibacterial activity, chiral HPLC behavior on polysaccharide- and protein-based stationary phases, molecular docking, and multivariate relationships were evaluated. Results: Target-dependent enantioselectivity and substituent-dependent activity patterns were observed. All enantiomeric pairs were chromatographically distinguished under at least one condition, and selected compounds showed selector- and mobile-phase-dependent changes in elution order. AGP-based chromatography showed stereoselective recognition for a subset of compounds, while computational analyses provided complementary support for the experimental trends. Conclusions: Stereochemistry and substitution jointly influence biological and chromatographic behavior in this thiourea series. Integrated biological, chromatographic, and computational profiling provides a useful framework for early enantiomer-resolved developability assessment.

Neisseria meningitidis is a bacterium that can cause high-mortality invasive infections. Asymptomatic carriage can serve as a source of infection. This study aimed to determine the meningococcal colonisation rate and risk factors for colonisation among children aged 1–6 years attending eight childcare institutions in three regions in the Northern part of Hungary. Oropharyngeal swab specimens were obtained from 180 children, and risk factors for carriage were assessed by questionnaires filled out by parents. qPCR was applied to detect meningococci and determine the serogroup. The meningococcal colonisation rate was 15.6% (28/180). One meningococcus detected belonged to serogroup X; all others were non-groupable meningococci. Meningococcal colonisation was significantly more prevalent among girls (21.5% vs. 9.2% in boys) and children living in the Central Transdanubia region. No significant association was found with other risk factors examined. According to the parental answers, 70.0% of the children were vaccinated against meningococcus; this might be an explanation for the absence of vaccine serogroups. This is the first study to examine meningococcal carriage among young children in Hungary.

Introduction: Paediatric acute haematogenous bone and joint infections (BJIs) are serious conditions. This study aimed to analyse the characteristics of paediatric acute haematogenous osteomyelitis (AHO) and septic arthritis (SA) in Hungary, with a focus on causative pathogens, clinical outcomes, and long-term complications. Methods: A retrospective cohort study was conducted at a Hungarian tertiary referral centre between 2015 and 2022. Children aged 18 years or younger diagnosed with acute haematogenous osteomyelitis (AHO) or septic arthritis (SA) within two months of symptom onset were included. Exclusion criteria were chronic infection, post-operative infections, or wound-related infections. Complicated AHO was defined by intraosseous abscess or necrosis confirmed radiologically or intraoperatively. The primary outcome was surgical intervention beyond 30 days after diagnosis; secondary outcomes included long-term complications. Results: Forty patients were included (77.5% male, median age 8.7 years). AHO was diagnosed in 8 patients (20.0%), complicated AHO in 22 (55.0%), and SA in 10 (25.0%). MRI had the highest diagnostic sensitivity (97.0%). Pathogens were identified in 72.5% of cases; Staphylococcus aureus (S. aureus) was most common (57.5%), followed by Salmonella and Streptococcus pyogenes (5% each). Surgery was required in 90.0% of SA cases, 77.2% of complicated AHO, and 37.5% of uncomplicated AHO. Long-term complications occurred in 10%, mainly with S. aureus and complicated AHO. Conclusions: Paediatric BJIs, especially due to S. aureus, often require surgery and cause long-term sequelae.

Nasopharyngeal carriage of Streptococcus pneumoniae in children plays a key role in transmission and disease epidemiology, hence it is crucial to monitor colonisation. As PCV-15 has recently replaced PCV-13 in Hungary, the aim of the study was to survey colonisation epidemiology 12–13 years post-PCV-13. 401 children, attending day care centres at Northern Hungary (including Budapest) were screened between April 2022 and April 2023. The samples were collected with cotton swabs from both nostrils, the serotype and antibiotic susceptibility of the isolates was determined. Overall, the carriage rate was 16.5% (66/401 children), which is lower compared to previous data from Hungary. Serotypes 23B, 35F, 15A/F, 15B/C, 11A and 23A were most prevalent. Non-vaccine types (NVTs) accounted for 68.2%, the coverage of PCV-13, PCV-15 and PCV-20 would be 9.1%, 10.6% and 31.8%, respectively. The resistance of the isolates to erythromycin, clindamycin and tetracycline was 12.1%, 7.6% and 10.6%, respectively and penicillin non-susceptibility was 24.2%. Serotypes 23B and 15A/F and 35F contributed mostly to resistance. In summary, prevalence of NVTs is increasing and these are associated with higher resistance rates. Among vaccine types, those included in PCV-20 are most prevalent. Hence, vaccination with the highest coverage could be recommended.

Methicillin-resistant Staphylococcus aureus bearing the mecC gene (mecC-MRSA) has been reported from animals and humans in recent years. This study describes the first mecC-MRSA isolates of human and equine origin in Hungary (two isolates from horses and one from a veterinarian, who treated one of the infected horses, but was asymptomatic). MRSA isolates were identified by cultivation and PCR detection of the species-specific spa gene and mecA/mecC methicillin resistance genes. The isolates were characterized by antibiotic susceptibility testing, MLST, spa, SCCmec typing, PFGE and whole genome sequencing (WGS). All three isolates belonged to the ST130-t843-SCCmec XI genotype, and carried the mecC and blaZ genes. Apart from beta-lactam drugs, they were sensitive to all tested antibiotics. The isolates of the infected horse and its veterinarian had the same PFGE pulsotype and showed only slight differences with WGS. Hence, this is the first description of direct transmission of a mecC-carrying MRSA between a horse and its veterinarian. The emergence of mecC in the country highlights the importance of the appropriate diagnostics in MRSA identification.

The formation of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) is one of the most common causes of morbidity and mortality in CF patients. Cyclic di-GMP and cyclic AMP are second messengers regulating the bacterial lifestyle transition in response to environmental signals. We aimed to investigate the effects of extracellular pH and bicarbonate on intracellular c-di-GMP and cAMP levels, and on biofilm formation. P. aeruginosa was inoculated in a brain–heart infusion medium supplemented with 25 and 50 mM NaCl in ambient air (pH adjusted to 7.4 and 7.7 respectively), or with 25 and 50 mM NaHCO₃ in 5% CO₂ (pH 7.4 and 7.7). After 16 h incubation, c-di-GMP and cAMP were extracted and their concentrations determined. Biofilm formation was investigated using an xCelligence real-time cell analyzer and by crystal violet assay. Our results show that HCO₃⁻ exposure decreased c-di-GMP and increased cAMP levels in a dose-dependent manner. Biofilm formation was also reduced after 48 h exposure to HCO₃⁻. The reciprocal changes in second messenger concentrations were not influenced by changes in medium pH or osmolality. These findings indicate that HCO₃⁻ per se modulates the levels of c-di-GMP and cAMP, thereby inhibiting biofilm formation and promoting the planktonic lifestyle of the bacteria.