Regulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2.

The cellular membrane in male meiotic germ cells contains a unique class of phospholipids and sphingolipids that is required for male reproduction. Here, we show that a conserved membrane fluidity sensor, AdipoR2, regulates the meiosis-specific lipidome in mouse testes by promoting the synthesis of sphingolipids containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs). AdipoR2 upregulates the expression of a fatty acid elongase, ELOVL2, both transcriptionally and post-transcriptionally, to synthesize VLC-PUFA. The depletion of VLC-PUFAs and subsequent accumulation of palmitic acid in AdipoR2 knockout testes stiffens the cellular membrane and causes the invagination of the nuclear envelope. This condition impairs the nuclear peripheral distribution of meiotic telomeres, leading to errors in homologous synapsis and recombination. Further, the stiffened membrane impairs the formation of intercellular bridges and the germ cell syncytium, which disrupts the orderly arrangement of cell types within the seminiferous tubules. According to our findings we propose a framework in which the highly-fluid membrane microenvironment shaped by AdipoR2-ELOVL2 underpins meiosis-specific chromosome dynamics in testes.

Carbapenemase-producing Klebsiella pneumoniae in community settings: a cross-sectional study in Belgrade, Serbia.

Aim: The types of carbapenemases and clonal relatedness among community isolates of carbapenemase-producing Klebsiella pneumoniae in Belgrade, Serbia, were determined. Materials & methods: During the period 2016-2020, K. pneumoniae community isolates were screened for carbapenemases, and carbapenemase production was confirmed by multiplex PCR. Clonality was determined based on genetic profiles obtained by enterobacterial repetitive intergenic consensus PCR. Results: Carbapenemase genes were detected in 114 of 4800 isolates (2.4%). The most frequent gene was blaOXA-48-like. Most isolates (70.5%) were grouped in ten clusters. Cluster 11 contained 16.4% of all blaOXA-48-like-positive isolates, and all blaKPC-positive isolates were grouped in one cluster. Conclusion: Laboratory-based detection and surveillance are highly recommended in order to control the spread of resistance in community settings.

The main threat of antimicrobial resistance is the ability of bacteria to exchange the genetic material on mobile genetic elements. Carbapenemases are a group of proteins that confer resistance to carbapenem antibiotics and their genes are commonly carried on mobile genetic elements. Five of these proteins have the greatest clinical importance: KPC, VIM, IMP, NDM and OXA-48. Serbia has one of the highest levels of carbapenemase-producing Klebsiella pneumoniae among hospital isolates in Europe, but there are no available data for community isolates. Thus, we analyzed K. pneumoniae isolates from community patients in Belgrade, Serbia. There was no difference between the number of isolates with carbapenemases in comparison with other European regions where similar studies have been conducted. The predominant carbapenemase among community isolates of K. pneumoniae in our study was OXA-48. In previous studies in our country, NDM carbapenemase was the most prevalent among both community and hospital isolates. This is in accordance with the endemicity of NDM enzymes in Balkan countries, but our results suggest that there could be changes in the molecular epidemiology of carbapenemases in Serbia, which should be confirmed by future research.

Antimicrobial Susceptibility and Molecular Characterization of Carbapenemase-Producing Enterobacter spp. Community Isolates in Belgrade, Serbia.

Antimicrobial resistance represents the emerging problem of modern medicine. Despite the fact that Enterobacter spp. is one of the most resistant pathogens, there has been a paucity of data on molecular epidemiology and antimicrobial susceptibility of community isolates in European countries as well as in Serbia. This study was conducted in 2016 and 2017 with the aim to investigate the prevalence of carbapenem-resistant Enterobacter spp. community isolates, molecular determinants of carbapenem resistance, and their genetic relatedness. Seventeen (1.6%) of 1,040 isolates that were positive for carbapenemase screening in accordance with European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations were included in the study. Minimum inhibitory concentrations for selected antimicrobials were determined by broth microdilution and by disk diffusion for chloramphenicol. Multiplex polymerase chain reactions (PCRs) for blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48-like carbapenemase genes were performed. Clonality was assessed by enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis. All isolates were multidrug resistant. The most frequent carbapenemase gene found was blaNDM (70.6%), followed by isolates coharboring blaNDM and blaOXA-48-like genes (23.5%) and a single isolate with the blaOXA-48-like gene (5.9%). ERIC-PCR molecular typing showed six different clusters (A-F) with clonal relatedness among isolates from the same institution and association of clusters E and F with the blaNDM carbapenemase gene. Our results indicate the need for Enterobacter spp. surveillance both in the community and hospitals to prevent spreading of multiresistant clones.