High frequency of Enterococcus faecalis detected in urinary tract infections in male outpatients - a retrospective, multicenter analysis, Germany 2015 to 2020.

BACKGROUND: Urinary tract infections (UTI) in men differ relevantly to women by their pathogens. Gram-positive uropathogens play a relevant role in UTI in men. In this study, we aimed to analyze the epidemiology of Enterococcus faecalis in UTI in male outpatients. METHODS: We conducted a retrospective observational multicenter study during 2015 to 2020 consisting of urine samples of 99,415 adult male outpatients sent from 6,749 outpatient practices from Germany. Proportions were compared using the z-Test and 95% confidence intervals were calculated using the Clopper-Pearson method. RESULTS: E. faecalis is the 2nd most frequent bacteria (16%) detected in suspected UTI in male outpatients. Young men are predominantly at risk (17%) for isolation of E. faecalis in suspected UTI. In polymicrobial infections E. faecalis is isolated in 47% of all suspected UTI in men. Recurrency of suspected UTI is significantly more frequent when E. faecalis is isolated compared to Escherichia coli (22% vs 26%; p < .001). Recurrency rates of E. faecalis associated UTI increases by age from 12% (18-29 years) to 28% ([Formula: see text] 70 years); p < .001. Congruently the resistance of E. faecalis against ciprofloxacin increases by age from 22% (18-29 years; 2019) to 37% ([Formula: see text] 70 years; 2019); p < .001. CONCLUSIONS: E. faecalis is frequently isolated in suspected UTI in male patients. Consequently, Nitrate-sticks results cannot be recommended to exclude UTI in men. The empirical use of ciprofloxacin in young adults can be reasonable. Frequent recurrences in E. faecalis associated suspected UTI emphasizes the importance of microbiological pathogen identification and susceptibility testing in men suffering from UTI.

High antimicrobial resistance in urinary tract infections in male outpatients in routine laboratory data, Germany, 2015 to 2020.

BackgroundEvidence on the distribution of bacteria and therapy recommendations in male outpatients with urinary tract infections (UTI) remains insufficient.AimWe aimed to report frequency distributions and antimicrobial resistance (AMR) of bacteria causing UTI in men and to identify risk factors for resistance of Escherichia coli against trimethoprim (TMP) and ciprofloxacin (CIP).MethodsWe conducted a retrospective observational study using routinely collected midstream urine specimens from 102,736 adult male outpatients sent from 6,749 outpatient practices to nine collaborating laboratories from all major regions in Germany between 2015 and 2020. Resistance in E. coli was predicted using logistic regression.ResultsThe three most frequent bacteria were E. coli (38.4%), Enterococcus faecalis (16.5%) and Proteus mirabilis (9.3%). Resistance of E. coli against amoxicillin (45.7%), TMP (26.6%) and CIP (19.8%) was common. Multiple drug resistance was high (22.9%). Resistance against fosfomycin (0.9%) and nitrofurantoin (1.9%) was low. Resistance of En. faecalis against CIP was high (29.3%). Isolates of P. mirabilis revealed high resistance against TMP (41.3%) and CIP (16.6%). The CIP and TMP resistance was significantly higher among bacteria derived from recurrent UTI (p < 0.05). Age ≥ 90 years, recurrent UTI and regions East and South were independently associated with AMR of E. coli against TMP and CIP (p < 0.05).ConclusionThe most frequent UTI-causing pathogens showed highresistance against TMP and CIP, empirical therapy is therefore likely to fail. Apart from intrinsically resistant pathogens, susceptibility to fosfomycin and nitrofurantoin remains sufficient. Therefore, they remain an additional option for empirical treatment of uncomplicated UTI in men.

Sumoylation Protects Against ß-Synuclein Toxicity in Yeast.

Aggregation of α-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD). The budding yeast Saccharomyces cerevisiae serves as reference cell to study the interplay between αSyn misfolding, cytotoxicity and post-translational modifications (PTMs). The synuclein family includes α, ß and γ isoforms. ß-synuclein (ßSyn) and αSyn are found at presynaptic terminals and both proteins are presumably involved in disease pathogenesis. Similar to αSyn, expression of ßSyn leads to growth deficiency and formation of intracellular aggregates in yeast. Co-expression of αSyn and ßSyn exacerbates the cytotoxicity. This suggests an important role of ßSyn homeostasis in PD pathology. We show here that the small ubiquitin-like modifier SUMO is an important determinant of protein stability and ßSyn-induced toxicity in eukaryotic cells. Downregulation of sumoylation in a yeast strain, defective for the SUMO-encoding gene resulted in reduced yeast growth, whereas upregulation of sumoylation rescued growth of yeast cell expressing ßSyn. This corroborates a protective role of the cellular sumoylation machinery against ßSyn-induced toxicity. Upregulation of sumoylation significantly reduced ßSyn aggregate formation. This is an indirect molecular process, which is not directly linked to ßSyn sumoylation because amino acid substitutions in the lysine residues required for ßSyn sumoylation decreased aggregation without changing yeast cellular toxicity. αSyn aggregates are more predominantly degraded by the autophagy/vacuole than by the 26S ubiquitin proteasome system. We demonstrate a vice versa situation for ßSyn, which is mainly degraded in the 26S proteasome. Downregulation of sumoylation significantly compromised the clearance of ßSyn by the 26S proteasome and increased protein stability. This effect is specific, because depletion of functional SUMO did neither affect ßSyn aggregate formation nor its degradation by the autophagy/vacuolar pathway. Our data support that cellular ßSyn toxicity and aggregation do not correlate in their cellular impact as for αSyn but rather represent two distinct independent molecular functions and molecular mechanisms. These insights into the relationship between ßSyn-induced toxicity, aggregate formation and degradation demonstrate a significant distinction between the impact of αSyn compared to ßSyn on eukaryotic cells.