Crossing of interspecies barriers by microorganisms is observed. In recent years, Staphylococcus pseudintermedius-a species formerly thought to be animal-has also been isolated from human clinical materials. Many virulence factors are responsible for the colonization, which is the first step an infection, of the new host organism. We analyzed the factors influencing this colonization as well as susceptibility to antibiotics in fourteen S. pseudintermedius strains isolated from clinical cases from humans and animals. The occurrence of genes responsible for binding elastin, fibronectin, and fibrinogen and some phenotypic features, although different between strains, is comparable in both groups. However, the animal isolates had more genes coding for virulence factors. All isolates tested had the exfoliating toxin gene and the leukotoxin determining genes, but only the human strains had enterotoxin genes. The assessment of antibiotic resistance of strains of both groups indicates their broad resistance to antibiotics commonly used in veterinary medicine. Antibiotic resistance was more common among animal isolates. The multilocus sequence typing analysis of the studied strains was performed. The results indicated a large diversity of the S. pseudintermedius population in both studied groups of strains. Equipped with important virulence factors, they showed the ability to infect animals and humans. The clonal differentiation of the methicillin-susceptible strains and the multidrug resistance of the strains of both studied groups should be emphasized. The considerable genetic diversity of strains from a limited geographical area indicates the processes of change taking place within this species. Thus, careful observation of the ongoing process of variation is necessary, as they may lead to the selection of S. pseudintermedius, which will pose a significant threat to humans.

• Klíčová slova
• Bacterial adhesions, Methicillin resistance, Staphylococcal infections, Staphylococcus, Zoonotic infections,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální léková rezistence MeSH
• faktory virulence genetika   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• stafylokokové infekce * veterinární   epidemiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• faktory virulence MeSH

Efflux transporters, namely ATP-binding cassette (ABC), are one of the primary reasons for cancer chemoresistance and the clinical failure of chemotherapy. Ganciclovir (GCV) is an antiviral agent used in herpes simplex virus thymidine kinase (HSV-TK) gene therapy. In this therapy, HSV-TK gene is delivered together with GCV into cancer cells to activate the phosphorylation process of GCV to active GCV-triphosphate, a DNA polymerase inhibitor. However, GCV interacts with efflux transporters that are responsible for the resistance of HSV-TK/GCV therapy. In the present study, it was explored whether GCV and its more lipophilic derivative (1) could inhibit effluxing of another chemotherapeutic, methotrexate (MTX), out of the human breast cancer cells. Firstly, it was found that the combination of GCV and MTX was more hemocompatible than the corresponding combination with compound 1. Secondly, both GCV and compound 1 enhanced the cellular accumulation of MTX in MCF-7 cells, the MTX exposure being 13-21 times greater compared to the MTX uptake alone. Subsequently, this also reduced the number of viable cells (41-56%) and increased the number of late apoptotic cells (46-55%). Moreover, both GCV and compound 1 were found to interact with breast cancer resistant protein (BCRP) more effectively than multidrug-resistant proteins (MRPs) in these cells. Since the expression of BCRP was higher in MCF-7 cells than in MDA-MB-231 cells, and the cellular uptake of GCV and compound 1 was smaller but increased in the presence of BCRP-selective inhibitor (Fumitremorgin C) in MCF-7 cells, we concluded that the improved apoptotic effects of higher MTX exposure were raised mainly from the inhibition of BCRP-mediated efflux of MTX. However, the effects of GCV and its derivatives on MTX metabolism and the quantitative expression of MTX metabolizing enzymes in various cancer cells need to be studied more thoroughly in the future.

• Klíčová slova
• MCF-7/MDA-MB-231 human breast cancer cells, breast cancer resistant protein (BCRP), ganciclovir (GCV), methotrexate (MTX), multidrug resistance (MDR),
• MeSH
• ABC transportér z rodiny G, člen 2 metabolismus   MeSH
• antivirové látky farmakologie   MeSH
• apoptóza účinky léků   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• ganciklovir farmakologie   MeSH
• lidé MeSH
• methotrexát farmakologie   MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny metabolismus   MeSH
• nádory prsu farmakoterapie   metabolismus   MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportér z rodiny G, člen 2 MeSH
• ABCG2 protein, human MeSH Prohlížeč
• antivirové látky MeSH
• ganciklovir MeSH
• methotrexát MeSH
• nádorové proteiny MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům MeSH

Staphylococcus pseudintermedius is a species often isolated from animals, as a common element of their microbiota or an agent of infection, and from people associated with an animal habitat, including owners of home pets-dogs and cats. As with many other species, adaptation of these bacteria to the human body can occur, and they become important human pathogens. 59 S. pseudintermedius strains were investigated in this study to determine the factors contributing to human body colonization: inhibition growth of human skin residents isolated from human skin (Staphylococcus epidermidis, Corynebacterium spp., Cutibacterium acnes (formerly Propionibacterium acnes)), biofilm formation, and the presence of ten genes encoding infection-promoting features (including ebpS, spsE, lukS, lukF, pvl, lip, hlgA, hlgB). The ability of human skin to be colonized and the presence of genes that promote the development of skin infections showed the significant potential of the studied strains in their adaptation to the host. However, while a comparison of the characteristics of animal strains and those isolated from human infections does not allow us to claim that we are the witnesses of the speciation of a new human pathogen, it does indicate their gradual adaptation to the human organism.

• Klíčová slova
• Colonization, Companion animals, Skin microflora, Staphylococcus pseudintermedius, Virulence,
• MeSH
• bakteriální geny MeSH
• fenotyp MeSH
• kočky MeSH
• lidé MeSH
• mikrobiota MeSH
• psi MeSH
• stafylokokové infekce mikrobiologie   přenos   MeSH
• Staphylococcus klasifikace   fyziologie   MeSH
• virulence MeSH
• zoonózy mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH