Authors:Ildikó Nyilasi, T. Papp, M. Takó, Erzsébet Nagy, and Cs. Vágvölgyi
Iron is an essential nutrient for most organisms because it serves as a catalytic cofactor in oxidation-reduction reactions. Iron is rather unavailable because it occurs in its insoluble ferric form in oxides and hydroxides, while in serum of mammalian hosts is highly bound to carrier proteins such as transferrin, so the free iron concentration is extremely low insufficient for microbial growth. Therefore, many organisms have developed different iron-scavenging systems for solubilizing ferric iron and transporting it into cells across the fungal membrane. There are three major mechanisms by which fungi can obtain iron from the host: (a) utilization of a high affinity iron permease to transport iron intracellularly, (b) production and secretion of low molecular weight iron-specific chelators (siderophores), (c) utilization of a hem oxygenase to acquire iron from hemin. Patients with elevated levels of available serum iron treated with iron chelator, deferoxamine to remedy iron overload conditions have an increased susceptibility of invasive zygomycosis. Presumably deferoxamine predisposes patients to Zygomycetes infections by acting as a siderophore. The frequency of zygomycosis is increasing in recent years and these infections respond very poorly to currently available antifungal agents, so new approaches to develop strategies to prevent and treat zygomycosis are urgently needed. Siderophores and iron-transport proteins have been suggested to function as virulence factors because the acquisition of iron is a crucial pathogenetic event. Biosynthesis and uptake of siderophores represent possible targets for antifungal therapy.
Pathogenicity and virulence are multifactorial traits, depending on interaction of viruses with susceptible cells and organisms. The ion channels coded by viruses, viroporins, represent only one factor taking part in the cascade of interactions between virus and cell, leading to the entry of virus, replication and to profound changes in membrane permeability. The M2 protein from influenza A virus forms proton-selective, pH-regulated channel involved in regulating vesicular pH, a function important for the correct maturation of HA glycoprotein. The NB glycoprotein of influenza B viruses is an integral membrane protein with an ion channel activity. The CM2 protein of influenza C virus is an integral membrane glycoprotein structurally analogous to influenza A virus M2 and influenza B virus NB proteins. The picornavirus 3A protein is involved in cell lysis and shows homology with other lytic proteins. Vpu is an oligomeric integral membrane protein encoded by HIV-1, which forms ion channels. The togavirus 6K protein shows structural similarities with other viroporins.
Advances in medical and surgical therapy over the past two decades have changed the nature of patient care during hospitalization. Recently developed technologies and therapies, involving bone marrow or solid-organ transplants and chemotherapeutic agents, have become common at many medical centers, resulting in the emergence of many immunocompromised individuals. In intensive care units (ICU) the use of invasive monitoring devices, parenteral nutrition, broad-spectrum antimicrobial agents, and assisted ventilation has helped in the treatment of patients suffering from previously devastating or fatal diseases and has provided opportunities for life to premature neonates previously thought to be non-viable . However, these successes have resulted in the proliferation of a severely ill, immunocompromised, long-lasting hospitalized patient population. The AIDS epidemic has also added patients at risk to this growing population of immunocompromised individuals . The immunocompromised patient is highly susceptible to nosocomial infections caused by organisms such as fungi that were previously considered to be of low virulence or „non-pathogenic” . Besides the well-known endemic fungal pathogens (Histoplasma capsulatumCoccidioides immitisandBlastomyces dermatitidis), opportunisticCandidaspecies have been implicated most frequently in nosocomial fungal infections.
Authors:G. Klausz, Andrea Tiszai, Zsuzsa Lénárt, Zsófia Gyulai, L. Tiszlavicz, Márta Hőgye, M. Csanády, J. Lonovics, and Yvette Mándi
The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease. The mucosal production of TNF-a, IL-6, IL-8 and IL-10 and the CagA status were investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antral mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H. pylori-positive (58 of 100) healthy blood donors. In complementary studies focusing on extragastric disease, it was found that 57% of patients with ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them had antibodies against human heat shock protein 60, too. This study suggests that, besides the bacterial virulence factor, the host response of an increased mucosal production of inflammatory cytokines can be relevant to the gastric pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart diseases the role of autoimmune processes induced by H. pylori cannot be excluded.
Authors:Ivan Dobrosavljević, Dejan Vidanović, Maja Velhner, Biljana Miljković, and Branislav Lako
Infectious bursal disease virus is an important poultry pathogen. It is distributed worldwide and causes significant economic losses. In this study, a system was adopted for the simultaneous monitoring of vaccine and virulent strains using reverse transcription polymerase chain reaction (RT-PCR). After the decay of maternal antibodies, chickens were vaccinated at the age of 37 days with a virus of intermediate virulence and challenged at 5, 10 and 14 days post vaccination (dpv). The challenge was done with IBDV strain CH/99. Sequencing of the hypervariable region of VP2 has shown that CH/99 belongs to the very virulent group of viruses. The vaccine virus could be found in the bursa of Fabricius, spleen, thymus and bone marrow until 24 dpv. The CH/99 challenge virus was found in the bursa and lymphoid organs when chickens were challenged at 5 and 10 dpv. When challenge was performed at 14 dpv, the pathogenic virus could not be found in the bursa and other lymphoid organs.
A szerző áttekinti az antibiotikumok és az antibiotikum-kutatás modern szemléletét, és összefoglalja a különféle – természetes, félszintetikus és szintetikus – antibiotikumoknak a kemoterápiában és más humánterápiás területeken betöltött jelenlegi szerepét. Vázolja az ismert és gyógyászatban alkalmazott antibiotikumok eredetét és más területeken (fiziológiás állapotok, mezőgazdaság) történő alkalmazásukat. Részletesen tárgyalja az elmúlt években felmerült problémákat, így a növekvő (poli)rezisztencia és virulencia témakörét és a nem tudományos, társadalmi, gazdasági, financiális kérdéseket. Röviden bemutatja a magyar antibiotikum-kutatás történetét. Ismerteti a jövőbeni kilátásokat és a természetes eredetű hatóanyagoknak a szintetikus szerekkel szembeni előnyeit. Új megközelítésekre hívja fel a figyelmet: a természet kimeríthetetlen élővilágában az új típusú, eddig nem vizsgált mikroorganizmusok és ezek bioszintetikus képességeinek jobb megismerését, valamint új biotechnológiai és genetikai módszerek (genomika, metagenomika, génbányászat) bevezetését. Orv. Hetil., 2013, 154, 563–573.
threshold concentration enter the cell, bind to regulatory protein, which then act as a transcription factor for several enzymes and virulence factor secretion genes [ 3, 4 ]. On the other hand, in Gram-positive bacteria, a precursor oligonucleotide molecule