Protein tyrosine phosphatases (PTPs) are increasingly recognized as important effectors of host-pathogen interactions. Since Guan and Dixon reported in 1990 that phosphatase YopH serves as an essential virulence determinant of Yersinia, the field shifted significantly forward, and dozens of PTPs were identified in various microorganisms and even in viruses. The discovery of extensive tyrosine signaling networks in non-metazoan organisms refuted the moth-eaten paradigm claiming that these organisms rely exclusively on phosphoserine/phosphothreonine signaling. Similarly to humans, phosphotyrosine signaling is thought to comprise a small fraction of total protein phosphorylation, but plays a disproportionately important role in cell-cycle control, differentiation, and invasiveness. Here we summarize the state-of-art knowledge on PTPs of important non-metazoan pathogens (Listeria monocytogenes, Staphylococcus aureus, Porphyromonas gingivalis, Caulobacter crescentus, Yersinia, Synechocystis, Leishmania, Plasmodium falciparum, Entamoeba histolytica, etc.), and focus also at the microbial proteins affecting directly or indirectly the PTPs of the host (Mycobacterium tuberculosis MTSA-10, Bacillus anthracis anthrax toxin, streptococcal β protein, Helicobacter pylori CagA and VacA, Leishmania GP63 and EF-1α, Plasmodium hemozoin, etc.). This is the first review summarizing the knowledge on biological activity and pharmacological inhibition of non-metazoan PTPs, with the emphasis of those important in host-pathogen interactions. Targeting of numerous non-metazoan PTPs is simplified by the fact that they act either as ectophosphatases or are secreted outside of the pathogen. Interfering with tyrosine phosphorylation represents a powerful pharmacologic approach, and even though the PTP inhibitors are difficult to develop, lifting the fog of phosphatase inhibition is of the great market potential and further clinical impact.

• MeSH
• Bacteria účinky léků   enzymologie   MeSH
• bakteriální proteiny antagonisté a inhibitory   metabolismus   MeSH
• inhibitory enzymů chemie   farmakologie   MeSH
• interakce hostitele a patogenu MeSH
• Leishmania účinky léků   enzymologie   MeSH
• lidé MeSH
• protozoální proteiny antagonisté a inhibitory   metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• tyrosinfosfatasy antagonisté a inhibitory   metabolismus   MeSH
• virové proteiny antagonisté a inhibitory   metabolismus   MeSH
• viry účinky léků   enzymologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Olomoucine II, the most recent derivative of roscovitine, is an exceptionally potent pharmacological inhibitor of cyclin-dependent kinase activities. Here, we report that olomoucine II is also an effective antiviral agent. METHODS: Antiviral activities of olomoucine II were tested on a range of human viruses in in vitro assays that evaluated viral growth and replication. RESULTS: Olomoucine II inhibited replication of a broad range of wild-type human viruses, including herpes simplex virus, human adenovirus type-4 and human cytomegalovirus. Olomoucine II also inhibited replication of vaccinia virus and herpes simplex virus mutants resistant to conventional acyclovir treatment. This report is the first demonstration of a poxvirus being sensitive to a cyclin-dependent kinase inhibitor. The antiviral effects of olomoucine II could be observed at lower concentrations than with roscovitine, although both were short-term. A remarkable observation was that olomoucine II, when used in combination with the DNA polymerase inhibitor cidofovir, was able to almost completely eliminate the spread of infectious adenovirus type-4 progeny from infected cells. CONCLUSIONS: Our results show that when targeting two complementary antiviral mechanisms, strongly additive effects could be observed.

• MeSH
• antivirové látky farmakologie   MeSH
• cyklin-dependentní kinasy antagonisté a inhibitory   MeSH
• fyziologie virů účinky léků   MeSH
• inhibiční koncentrace 50 MeSH
• inhibitory proteinkinas farmakologie   MeSH
• lidé MeSH
• puriny farmakologie   MeSH
• replikace viru účinky léků   MeSH
• viry enzymologie   růst a vývoj   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

The aim of the brief survey of natural antibiotics is to show the importance of this group of renewable materials. The examples of these secondary metabolites which are frequently utilized in human and veterinary medicine demonstrate their structural diversity.

• MeSH
• aminoglykosidy dějiny   farmakologie   terapeutické užití   MeSH
• antibakteriální látky dějiny   farmakologie   terapeutické užití   MeSH
• Bacteria enzymologie   izolace a purifikace   MeSH
• beta-laktamy dějiny   farmakologie   terapeutické užití   MeSH
• financování organizované MeSH
• glykosidy dějiny   farmakologie   terapeutické užití   MeSH
• houby enzymologie   izolace a purifikace   MeSH
• infekce etiologie   farmakoterapie   MeSH
• léčivé přípravky dějiny   izolace a purifikace   MeSH
• léková rezistence genetika   imunologie   účinky léků   MeSH
• lidé MeSH
• makrocyklické laktamy dějiny   farmakologie   terapeutické užití   MeSH
• makrolidy dějiny   farmakologie   terapeutické užití   MeSH
• mikrobiologie trendy   MeSH
• peptidy dějiny   farmakologie   terapeutické užití   MeSH
• tetracykliny dějiny   farmakologie   terapeutické užití   MeSH
• viry enzymologie   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• Bacteria enzymologie   metabolismus   růst a vývoj   MeSH
• Eukaryota enzymologie   metabolismus   růst a vývoj   MeSH
• houby enzymologie   metabolismus   růst a vývoj   MeSH
• kultivace virů MeSH
• kultivační média MeSH
• mikrobiální genetika MeSH
• teoretické modely MeSH
• viry enzymologie   metabolismus   růst a vývoj   MeSH
• zdravotnické prostředky MeSH
• Publikační typ
• bibliografie MeSH