The effect of TRIM5 variants on the susceptibility to HIV-1 infection and disease progression in the Polish population.

BACKGROUD: Tripartite motif containing 5α protein is a factor contributing to intracellular defense mechanisms against human immunodeficiency virus-1 (HIV-1) infection. The studies of TRIM5 variants effects on the risk of HIV-1 infection and the clinical course of disease provided inconclusive results in different ethnic groups. The aim of this study was to investigate the influence of TRIM5 variants on susceptibility to HIV-1 infection and clinical parameters among Polish HIV-1-infected patients. MATERIALS & METHODS: In our study, we investigated 301 HIV-1-infected patients and 186 age-matched seronegative controls. Seven variants of the TRIM5 gene (rs7127617, rs3824949, rs3740996, rs11601507, rs10838525, rs11038628, and rs28381981) were genotyped using both sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. RESULTS AND CONCLUSIONS: The frequencies of rs7127617 TT genotype and T allele occurrence were lower in HIV-1-infected subjects compared to controls (0.14 vs. 0.26 for T/T genotype and 0.45 vs. 0.54 for T allele), suggesting their possible protective effect (p = 0.005 and p = 0.007, respectively). Heterozygosity and presence of the T allele at rs3740996 were enriched in controls compared to HIV-1-infected group (0.19 vs. 0.12 for C/T genotype and 0.11 vs. 0.07 for T allele; p = 0.03 and p = 0.02, respectively). Moreover, rs3824949 CC genotype carriers had a lower viral load than patients bearing rs3824949 GG/CG genotypes (4.0 vs. 4.6 log copies/mL; p = 0.049); however, none of the variants affected CD4+ cell count. In conclusion, our data confirm the role of TRIM5 variants in the HIV-1 transmission and the clinical course of HIV-1 infection. The presence of rs7127617 TT genotype and T allele seems to protect against HIV-1 transmission in examined population.

The Direction of the Antibacterial Effect of Rutin Hydrate and Amikacin.

The aim of the presented study was to examine the in vitro antimicrobial activity of rutin hydrate (RH) alone and in combination with amikacin against 12 reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity assay was evaluated in the concentration range of 2-2048 µg/mL. A serial microdilution method was used to determine the minimal inhibitory concentration (MIC) of the examined compound against reference strains. RH showed varying potential against the tested strains with MICs ranging from 128 to 1024 µg/mL. In order to examine the combinatory profile of RH and amikacin, the fractional inhibitory concentrations (FICs) were determined. The RH-amikacin combination was more active against Gram-negative bacteria where four synergism and two additive interactions were noted. For four out of six Gram-positive isolates, an indifferent effect of RH and amikacin was demonstrated, and for two strains, the tested combination had an additive effect. The results of this study showed that RH possesses antimicrobial potential in vitro towards the tested reference isolates. Moreover, it shows a promising combined effect with amikacin against Gram-negative bacteria.

The Array of Antibacterial Action of Protocatechuic Acid Ethyl Ester and Erythromycin on Staphylococcal Strains.

The spread of antibiotic resistance among bacteria has become one of the major health problems worldwide. Methicillin-resistant staphylococcal strains are especially dangerous because they are often resistant to other antibiotics. The increasing insensitivity to macrolides, lincosamides and streptogramin B antibiotics of methicillin-resistant staphylococcal isolates has limited the use of these drugs in therapy. The combination of natural compounds and antibiotics can be considered as an alternative tool to fight multi-drug-resistant pathogen infections. The aim of the presented study was to examine the antibacterial activity of protocatechuic acid ethyl ester-erythromycin combination towards Staphylococcus aureus and Staphylococcus epidermidis strains with various resistance profiles to methicillin and macrolides, lincosamides and streptogramin B (MLSB) antibiotics. The in-vitro antibacterial potential of the above combination was investigated by minimum inhibitory concentration assays and checkerboard testing. The observed effects were strain dependent, with 8 of 12 tested staphylococcal strains showing an indifferent effect on the natural compound and erythromycin; for 2 strains, the tested combination had an additive effect, while for another 2, the effect was synergistic. Interestingly, the multi-drug-resistant strains were more sensitive to the cooperative action of the protocatechuic acid ethyl ester and the antibiotic.

From Alpha to Delta-Genetic Epidemiology of SARS-CoV-2 (hCoV-19) in Southern Poland.

In Poland, the first case of SARS-CoV-2 infection was confirmed in March 2020. Since then, many circulating virus lineages fueled rapid pandemic waves which inflicted a severe burden on the Polish healthcare system. Some of these lineages were associated with increased transmissibility and immune escape. Mutations in the viral spike protein, which is responsible for host cell recognition and serves as the primary target for neutralizing antibodies, are of particular importance. We investigated the molecular epidemiology of the SARS-CoV-2 clades circulating in Southern Poland from February 2021 to August 2021. The 921 whole-genome sequences were used for variant identification, spike mutation, and phylogenetic analyses. The Pango B.1.1.7 was the dominant variant (n = 730, 89.68%) from March 2021 to July 2021. In July 2021, the B.1.1.7 was displaced by the B.1.617.2 lineage with 66.66% in July 2021 and 92.3% in August 2021 frequencies, respectively. Moreover, our results were compared with the sequencing available on the GISAID platform for other regions of Poland, the Czech Republic, and Slovakia. The analysis showed that the dominant variant in the analyzed period was B.1.1.7 in all countries and Southern Poland (Silesia). Interestingly, B.1.1.7 was replaced by B.1.617.2 earlier in Southern Poland than in the rest of the country. Moreover, in the Czech Republic and Slovakia, AY lineages were predominant at that time, contrary to the Silesia region.

Mechanisms of Resistance to Macrolide Antibiotics among Staphylococcus aureus.

Methicillin resistant Staphylococcus aureus strains pose a serious treatment problem because of their multi-drug resistance (MDR). In staphylococcal strains, resistance to macrolides, lincosamides, and streptogramin B (MLSB) correlates with resistance to methicillin. The rapid transmission of erm genes responsible for MLSB resistance has strongly limited the clinical application of traditional macrolides such as erythromycin. On the other hand, in the age of increasing insensitivity to antibiotics the idea of implementing a therapy based on older generation drugs brings hope that the spread of antibiotic resistance will be limited. A thorough understanding of the resistance mechanisms contributes to design of antibiotics that avoid bacterial insensitivity. This review highlights the mechanisms of action of macrolides and mechanism of resistance to these antibiotics among Staphylococcus aureus.

Phenolic Compounds Diminish Antibiotic Resistance of Staphylococcus Aureus Clinical Strains.

There is a growing body of evidence that flavonoids show antibacterial activity against both Gram-positive and Gram-negative bacteria. The mechanisms of action of phenolic compounds on bacterial cell have been partially attributed to damage to the bacterial membrane, inhibition of virulence factors such as enzymes and toxins, and suppression of bacterial biofilm formation. What is more, some natural polyphenols, aside from direct antibacterial activity, exert a synergistic effect when combined with common chemotherapeutics. Many studies have proved that in synergy with antibiotics plant flavonoids pose a promising alternative for therapeutic strategies against drug resistant bacteria. In this review most recent reports on antimicrobial action of polyphenols on Staphylococcus aureus strains are described, highlighting where proven, the mechanisms of action and the structure⁻activity relationships. Since many reports in this field are, to some extent, conflicting, a unified in vitro and in vivo susceptibility testing algorithms should be introduced to ensure the selection of effective antibacterial polyphenolic compounds with low cytotoxicity and minimal side effects.

Antimicrobial Potential of Caffeic Acid against Staphylococcus aureus Clinical Strains.

Phenolic compounds constitute one of the most promising and ubiquitous groups with many biological activities. Synergistic interactions between natural phenolic compounds and antibiotics could offer a desired alternative approach to the therapies against multidrug-resistant bacteria. The objective of the presented study was to assess the antibacterial potential of caffeic acid (CA) alone and in antibiotic-phytochemical combination against Staphylococcus aureus reference and clinical strains isolated from infected wounds. The caffeic acid tested in the presented study showed diverse effects on S. aureus strains with the minimum inhibitory concentration (MIC) varied from 256 µg/mL to 1024 µg/mL. The supplementation of Mueller-Hinton agar (MHA) with 1/4 MIC of CA resulted in augmented antibacterial effect of erythromycin, clindamycin, and cefoxitin and to the lesser extent of vancomycin. The observed antimicrobial action of CA seemed to be rather strain than antibiotic dependent. Our data support the notion that CA alone exerts antibacterial activity against S. aureus clinical strains and has capacity to potentiate antimicrobial effect in combination with antibiotics. The synergy between CA and antibiotics demonstrates its potential as a novel antibacterial tool which could improve the treatment of intractable infections caused by multidrug-resistant strains.