Antibiotic resistance is one of the biggest threats to modern medicine. Response to antimicrobial treatment is seriously disrupted by aminoglycoside phosphotransferases (Aph) — enzymes produced by bacteria. The aph genes were annotated in many bacterial species, including commensals of the gut microbiota that can transfer these genes to clinically important strains. For this study we prepared a catalog of 21 aph genes. The in silico analysis of 11 intestinal microbiomes of healthy Russians revealed the presence of 3 cataloged aph genes in 7 microbiota samples, namely aph(3'')-Ib, aph(3')-IIIa and aph(2'')-Ia. The most frequent was the aph(3')-IIIa gene detected in 6 metagenomes. Of note, this gene was first discovered in Enterococcus faecalis, but in this study we observed it in sequences typical for commensal Ruminococcus obeum and opportunistic Enterococcus faecium, Roseburia hominis, Streptococcus pyogenes and Staphylococcus epidermidis.  Similarly, aph(2'')-Ia originally present in E. faecalis was detected in a sequence typical for Clostridium difficile. Our findings are consistent with the reports on the strong association between the geographical origin of the individual and frequency of aph genes. We suggest that clinical examination should include antibiotic sensitivity tests run not only on the causative agent, but also on the gut microbiota, for a better treatment outcome.
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Management of purulent wounds is a problem that requires particular attention: wounds are a common injury type for which suppurative complications are frequent, mortality rates are high and antimicrobial therapy may be ineffective due to the presence of drug-resistant bacteria in the wound. In this work we have studied the effectiveness of wound treatment with the leaf extract of transgenic Kalanchoe pinnata modified to produce antimicrobial peptide cecropin P1. Purulent wounds infected with Staphylococcus aureus were modeled in Wistar rats. Four groups of animals were formed, with 10 animals in each group. In all groups, the wounds were cleansed with 3 % hydrogen peroxide solution once a day; all groups except the controls received additional treatment. Group 2 received 10 % cefazolin solution, group 3 received kalanchoe juice, group 4 received the juice of cecropin P1-producing kalanchoe. Histologic stains of biopsy samples were performed after rats were sacrificed by anesthetic overdose on days 3, 10 and 14 after treatment onset. On day 3, wound dynamics was the same in all groups. On day 10 exudate was still observed in the controls; in group two exudation was almost finished and regeneration was about to begin; in groups 3 and 4 the wound defect was filled with granulation tissue. In spite of epidermal repair along the wound edges in groups 2 and 3, there still was some sloughing and granulation tissue was less mature than in group 4. We recommend conducting more extensive clinical research of the leaf extract of cecropin P1-containing transgenic Kalanchoe pinnata.
VIEWS 5792
Antiretroviral therapy (ART) for HIV-positive patients allowed labeling the disease a therapeutically controlled one. The main goal of ART is to prolong patient's life and preserve its quality. This is accomplished through viral load reduction (decrease of the number of HIV-RNA copies in blood plasma), which leads to the growing numbers of CD4<sup>+</sup>-T-lymphocytes. However, ART can be ineffective. In 2010–1014, we conducted an observational cohort retro/prospective study aimed at learning how often ART can be ineffective from immunological (II), virological (VI) and clinical points of view. The study was carried out at the premises of the Republic Center of AIDS and Infectious Diseases (Kazan, Russia). The study included 341 adult HIV-positive patients subjected to ART at 3rd and 4th stages of disease's development, with the treatment virologically efficient at least during the first year. The observation period was 1 to 3 years. ART was considered II (immunologically inefficient) when the number of CD4<sup>+</sup> increased for less than 50 cells/mcl through the year with HIV completely suppressed. VI (virological inefficiency) of ART was registered if the number of HIV RNA copies was above the definition threshold after 6 months of treatment. ART was II in 14.0–15.9 % of cases after a year of treatment and in 22 % of cases after three years. It was noted that subsequent restoration of an adequate number of T-lymphocytes CD4<sup>+</sup> required they overcame the threshold of 100 cells/mcl within the 1st year of treatment. Virologically, ART was effective for 92.7 % for patients. Most (80 %) cases of VI of ART were results of patients' lax attitude towards treatment. Clinically, ART helped 91 % of patients; this result largely depended on the number participants for whom ART was II. II of ART is a risk factor, the risk being progression of the disease with active ART in the background and death of the HIV-positive individual. II of ART makes the risk of clinical progression of HIV 6.232 times higher (95 % CI 3.106–12.51).
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