Investigating the antibacterial activity of salen/salophene metal complexes: Induction of ferroptosis as part of the mode of action.

The continuous increase of resistant bacteria including Staphylococcus aureus and its methicillin-resistant phenotype (MRSA) is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of drugs to fight against infections caused by these bacteria is urgently needed. In this structure-activity relationship study, metal-based drugs were investigated for the treatment of resistant pathogens. The selected Ni(II), Cu(II), Zn(II), Mn(III), and Fe(II/III) complexes differ in their salen- and salophene-type Schiff base ligands. The in vitro activity was evaluated using gram-positive (S. aureus and MRSA) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Especially the iron(III) complexes displayed promising antimicrobial effects against gram-positive bacteria, with MIC90 values ranging from 0.781 to 50 µg/mL. Among them, chlorido[(N,N'-bis(salicylidene)-1,2-phenylenediamine]iron(III) (6) showed the best MIC90 value (0.781 µg/mL = 1.93 µmol/L) against S. aureus and MRSA. Complex 6 was comparably potent as ciprofloxacin against S. aureus (0.391 µg/mL = 1.18 µmol/L) and only marginally less active than tetracycline against MRSA (0.391 µg/mL = 0.88 µmol/L). As part of the mode of action, ferroptosis was identified. Applying compound 6 (10 µg/mL), both gram-positive strains grown in PBS were killed within 20 min. This efficacy basically documents that salophene iron(III) complexes represent possible lead structures for the further development of antibacterial metal complexes.

Time-lapse imaging of cytoplasmic strings at the blastocyst stage suggests their association with spontaneous blastocoel collapse.

RESEARCH QUESTION: To study the origin and temporal behaviour of cytoplasmic strings spanning the blastocoel (main objective) and their influence on treatment outcome (secondary objective). DESIGN: This retrospective analysis of prospectively collected data was set up in a university medical centre. Patients who either underwent fresh (n = 95) or vitrified-warmed (n = 55) single blastocyst transfer were included. Time-lapse sequences of in-vitro developed blastocysts were screened for the presence of cytoplasmic strings. Pregnancies in string-positive and string-negative transfers were followed up to live birth. RESULTS: A total of 387 blastocysts were obtained in the fresh cycles of 100 patients, corresponding to a blastocyst formation rate of 62.4%. Cytoplasmic strings were first detected around full stage (108.5 ± 6.4 h) in 170 blastocysts (43.9%). The number of strings varied (range: 1-7) and the duration of visibility was 5.2 ± 3.5 h. The occurrence of cytoplasmic strings was significantly associated with the presence of blastocoelic collapses (P < 0.001) but not with any of the annotated morphokinetic parameters. Live birth and neonatal outcome were the same for both string-positive and string-negative pregnancies. Moreover, collapses did not affect treatment outcome. CONCLUSION: Time-lapse analysis of cytoplasmic strings at the blastocyst stage revealed that this morphological feature was not a negative predictor as previously reported. Although physiologically normal, at least some of the cytoplasmic strings are an artefact, possibly associated with blastocoelic collapses.

"Enhanced acquisition of antibiotic-resistant intestinal E. coli during the first year of life assessed in a prospective cohort study".

Background: Increasing bacterial resistance to antibiotics is a serious problem worldwide. We sought to record the acquisition of antibiotic-resistant Escherichia coli (E. coli) in healthy infants in Northern Thailand and investigated potential determinants. Methods: Stool samples from 142 infants after birth, at ages 2wk, 2mo, 4 to 6mo, and 1y, and parent stool samples were screened for E. coli resistance to tetracycline, ampicillin, co-trimoxazole, and cefazoline by culture, and isolates were further investigated for multiresistance by disc diffusion method. Pulsed-field gel electrophoresis was performed to identify persistent and transmitted strains. Genetic comparison of resistant and transmitted strains was done by multilocus sequence typing (MLST) and strains were further investigated for extra- and intra-intestinal virulence factors by multiplex PCR. Results: Forty-seven (33%) neonatal meconium samples contained resistant E. coli. Prevalence increased continuously: After 1y, resistance proportion (tetracycline 80%, ampicillin 72%, co-trimoxazole 66%, cefazoline 35%) almost matched those in parents. In 8 infants (6%), identical E. coli strains were found in at least 3 sampling time points (suggesting persistence). Transmission of resistant E. coli from parents to child was observed in only 8 families. MLST showed high diversity. We could not identify any virulence genes or factors associated with persistence, or transmission of resistant E. coli. Full-term, vaginal birth and birth in rural hospital were identified as risk factors for early childhood colonization with resistant E. coli. Conclusion: One third of healthy Thai neonates harboured antibiotic-resistant E. coli in meconium. The proportion of resistant E. coli increased during the first year of life almost reaching the value in adults. We hypothesize that enhancement of infection control measures and cautious use of antibiotics may help to control further increase of resistance.