Search bioRxivSearch

Biology subjects

Govorun, V. M.

Publications and source records attributed to Govorun, V. M..

3 recordsLinked to original sources

Far beyond common leeching: insights into an ancient medical device through integrated omics data

Salivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today. We annotated the Hirudo medicinalis genome and performed RNA-seq on salivary cells isolated from three closely related leech species, H. medicinalis, Hirudo orientalis, and Hirudo verbana. Differential expression analysis verified by proteomics identified salivary cell-specific genes, many of which encode previously unknown salivary components. However, the genes encoding known anticoagulants were not differentially expressed in the salivary cells. The function-related analysis of the unique salivary cell genes enabled an update of the concept of interactions between salivary proteins and components of haemostasis. Thus, our study provides one of the most comprehensive knowledge of the genetic fundamentals of the blood-sucking lifestyle in leeches.

systems biology

Shifts in the gut microbiota structure caused by Helicobacter pylori eradication therapy

The human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. Here we report a whole genome sequencing metagenomic study of the intestinal microbiota changes caused by Helicobacter pylori eradication therapy. We have found the decrease in taxonomic alpha-diversity due to the therapy. The changes observed were more extensive for patients with duodenal ulcer and female ones. As well across the patients under the therapy we have detected the shifts in the metabolic potential and resistome. Seven KEGG pathways associated with quorum sensing, genetic Information processing and environmental Information processing were increased, while metabolic pathways related with metabolism of cofactors and vitamins and glycan biosynthesis and metabolism decreased. Changes in the resistome profile have also been identified. We observed perturbations in intraspecies structures, which were higher in group of patients under the therapy than in control group of people without treatment. The Eubacterium rectale pangenome extracted from metagenomic data were changed. We also isolated and sequenced Enterococcus faecium strains from two patients before and after eradication therapy. After the therapy this bacterium increased as the antibiotic resistance in vitro, as well the number of ARGs to macrolides and tetracyclines and metagenomic relative abundance in comparison with strains before therapy. In summary, microbial community demonstrated shift to reduce metabolic potential and to increased mechanisms, which mediate more survival condition through intraspecies perturbations.\n\nImportanceThe human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. H. pylori eradication therapy causes multiple shifts and alterations (including intraspecies changes) of the intestinal microbiota structure and leads to the accumulation of genes which determine resistance to macrolides. Since these changes are not the same for patients with various diseases, patients with duodenal ulcer may be further paid special attention for reducing side effects, such as antibiotic-induced dysbiosis. Also, study of antibiotic treatment in terms of its impact upon the human gut microbiota allows shedding light on of the complex processes that cause accumulation and spread of antibiotic resistance. An identification and understanding of these complicated processes may help to constrain antibiotic resistance spread, which is of great importance for human health care.

microbiology

ACI-1 class A beta-lactamase is widespread across human gut microbiomes due to transposons harboured by tailed prophages

Antibiotic resistance is increasing among pathogens at unprecedented rates and the human body contains a large pool of antibiotic resistance genes that can be spread among bacteria by mobile genetic elements. Acidaminococcus intestini, a bacterium found in the human gut that belongs to the class of Negativicutes, is the first gram-negative coccus shown to be resistant to beta-lactam antibiotics. Resistance is conferred by aci1, a gene encoding the ACI-1 class A beta-lactamase, but the evolutionary history of aci1 and its distribution across other Negativicutes and in the human gut microbiota remains obscure. We discovered that ACI-1 proteins are phylogenetically distinct from class A beta-lactamases of gram-positive Firmicutes and that the aci1 gene occurs in bacteria scattered across the Negativicutes clade, suggesting possible mobilization. In the reference A. intestini RyC-MR95 strain, we found that aci1 is surrounded by mobile DNA, transposon derived sequences directly flank aci1 and are likely the vehicle for its mobility. These transposon sequences reside within a prophage context consisting of two likely degraded tailed prophages, the first prophages to be characterised in A. intestini. We found aci1 in at least 56 (4.4%) out of 1,267 human gut metagenome samples, mostly hosted within A. intestini, and, where could be determined, mostly within a similar constellation of mobile elements to that found in the reference A. intestini genome. These human samples are from individuals in Europe, China and the USA, showing that aci1 is widely distributed globally. Additionally, we examined the nine different Negativicute genome assemblies that contain aci1, and found that only two of these strains show a similar mobile element context around aci1 to the reference A. intestini with transposons adjacent to a tailed prophage. However, in all nine cases aci1 is flanked by transposon derived sequences, and these sequences are diverse, suggesting the activity and degradation of multiple transposons. Overall, we show that ACI-1 proteins form a distinct class A beta lactamase family, and that the aci1 gene is present in human guts worldwide within Negativicute bacterial hosts, due to transposons, sometimes inserted into tailed prophages.

microbiology