The Ability of Lytic Staphylococcal Podovirus vB_SauP_phiAGO1.3 to Coexist in Equilibrium With Its Host Facilitates the Selection of Host Mutants of Attenuated Virulence but Does Not Preclude the Phage Antistaphylococcal Activity in a Nematode Infection Model

Phage vB_SauP_phiAGO1.3 (phiAGO1.3) is a polyvalent Staphylococcus lytic podovirus with a 17.6-kb genome (Gozdek et al., 2018). It can infect most of the Staphylococcus aureus human isolates of dominant clonal complexes. We show that a major factor contributing to the wide host range of phiAGO1.3 is a lack or sparcity of target sites for certain restriction-modification systems of types I and II in its genome. Phage phiAGO1.3 requires for adsorption β-O-GlcNAcylated cell wall teichoic acid, which is also essential for the expression of methicillin resistance. Under certain conditions an exposure of S. aureus to phiAGO1.3 can lead to the establishment of a mixed population in which the bacteria and phages remain in equilibrium over multiple generations. This is reminiscent of the so called phage carrier state enabling the co-existence of phage-resistant and phage-sensitive cells supporting a continuous growth of the bacterial and phage populations. The stable co-existence of bacteria and phage favors the emergence of phage-resistant variants of the bacterium. All phiAGO1.3-resistant cells isolated from the phage-carrier-state cultures contained a mutation inactivating the two-component regulatory system ArlRS, essential for efficient expression of numerous S. aureus virulence-associated traits. Moreover, the mutants were unaffected in their susceptibility to infection with an unrelated, polyvalent S. aureus phage of the genus Kayvirus. The ability of phiAGO1.3 to establish phage-carrier-state cultures did not preclude its antistaphylococcal activity in vivo in an S. aureus nematode infection model. Taken together our results suggest that phiAGO1.3 could be suitable for the therapeutic application in humans and animals, alone or in cocktails with Kayvirus phages. It might be especially useful in the treatment of infections with the majority of methicillin-resistant S. aureus strains

Studies of Streptococcus anginosus Virulence in Dictyostelium discoideum and Galleria mellonella Models

For many years, Streptococcus anginosus has been considered a commensal colonizing the oral cavity, as well as the gastrointestinal and genitourinary tracts. However, recent epidemiological and clinical data designate this bacterium as an emerging opportunistic pathogen. Despite the reported pathogenicity of S. anginosus, the molecular mechanism underpinning its virulence is poorly described. Therefore, our goal was to develop and optimize efficient and simple infection models that can be applied to examine the virulence of S. anginosus and to study host-pathogen interactions. Using 23 S. anginosus isolates collected from different infections, including severe and superficial infections, as well as an attenuated strain devoid of CppA, we demonstrate for the first time that Dictyostelium discoideum is a suitable model for initial, fast, and large-scale screening of virulence. Furthermore, we found that another nonvertebrate animal model, Galleria mellonella, can be used to study the pathogenesis of S. anginosus infection, with an emphasis on the interactions between the pathogen and host innate immunity. Examining the profile of immune defense genes, including antimicrobial peptides, opsonins, regulators of nodulation, and inhibitors of proteases, by quantitative PCR (qPCR) we identified different immune response profiles depending on the S. anginosus strain. Using these models, we show that S. anginosus is resistant to the bactericidal activity of phagocytes, a phenomenon confirmed using human neutrophils. Notably, since we found that the data from these models corresponded to the clinical severity of infection, we propose their further application to studies of the virulence of S. anginosus

The "new" and "old" antibiotics - mechanisms of action and strategies for development of novel antibacterial agents.

Narastająca oporność bakterii na dostępne obecnie antybiotyki stanowi niezmiernie duży problem w terapii zakażeń. Na świecie zanotowano pojawienie się bakterii niosących wiele genów warunkujących oporność, efektem tego może być niewrażliwość na wszystkie dostępne klasy antybiotyków, jak to miało ostatnio miejsce w przypadku bakterii opornych na kolistynę. Kolistyna to lek ostatniej szansy w przypadku leczenia infekcji wywołanych bakteriami opornymi na antybiotyki β-laktamowe. Współcześnie dostępne klasy antybiotyków mają różne cele, takie jak osłony komórkowe, i procesy w komórce takie jak hamowanie syntezy białek, transkrypcja, replikacja, czy zaburzenia szlaków syntezy niektórych metabolitów w komórkach bakterii. Ciągle jednak trwa swojego rodzaju "wyścig zbrojeń" i poszukiwania nowych sposobów walki z opornymi mikroorganizmami. Stosowane są nowe strategie lepszego wykorzystania stosowanych już antybiotyków np. przez poszukiwanie synergistycznych oddziaływań pomiędzy lekami lub stosowanie różnego rodzaju dodatków zwiększających ich skuteczność, poszukiwanie nowych substancji i nowych celów komórkowych oraz strategie zmniejszania zjadliwości bakterii podczas infekcji.Constantly increasing resistance of bacteria to available antibiotics is a real clinical problem. In recent years we observed a dramatic increase in number of multi resistant, so called MDR and XDR strains, causing some bacteria to become resistant to all classes of antibiotics. One recent example is the raise of collistin resistant strains while collistin has been an antibiotic of last resort in treatment of infections caused by bacteria resistant to β-lactam antibiotics. Currently available classes of antibiotics have various cellular targets. They may affect cell envelope, processes such as replication, transcription and translation and affect cellular metabolism. Today’s situation reminds the Red Queen’s Race when we try to develop new antibiotics, but constantly deal with antibiotic resistance. However, new strategies are being applied to develop active antimicrobial substances. Such strategies include: (i) better use of “old” antibiotics by using them in synergistic combinations or in combinations with small molecule additives, (ii) search for new active substances, and for new cell targets, and (iii) lowering of bacterial virulence during the infection

The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer

Lung cancer is a disease that in recent years has become one of the greatest threats to modern society. Every year there are more and more new cases and the percentage of deaths caused by this type of cancer increases. Despite many studies, scientists are still looking for answers regarding the mechanisms of lung cancer development and progression, with particular emphasis on the role of the immune system. The aim of this literature review was to present the importance of disorders of the immune system and the accompanying changes at the level of cell signaling in the pathogenesis of lung cancer. The collected results showed that in the process of immunopathogenesis of almost all subtypes of lung cancer, changes in the tumor microenvironment, deregulation of immune checkpoints and abnormalities in cell signaling pathways are involved, which contribute to the multistage and multifaceted carcinogenesis of this type of cancer. We, therefore, suggest that in future studies, researchers should focus on a detailed analysis of tumor microenvironmental immune checkpoints, and to validate their validity, perform genetic polymorphism analyses in a wide range of patients and healthy individuals to determine the genetic susceptibility to lung cancer development. In addition, further research related to the analysis of the tumor microenvironment; immune system disorders, with a particular emphasis on immunological checkpoints and genetic differences may contribute to the development of new personalized therapies that improve the prognosis of patients

A decade of invasive meningococcal disease surveillance in Poland.

Neisseria meningitidis is a leading etiologic agent of severe invasive disease. The objective of the study was to characterise invasive meningococcal disease (IMD) epidemiology in Poland during the last decade, based on laboratory confirmed cases.The study encompassed all invasive meningococci collected between 2002 and 2011 in the National Reference Centre for Bacterial Meningitis. The isolates were re-identified and characterised by susceptibility testing, MLST analysis, porA and fetA sequencing. A PCR technique was used for meningococcal identification directly from clinical materials.In the period studied, 1936 cases of IMD were confirmed, including 75.6% identified by culture. Seven IMD outbreaks, affecting mostly adolescents, were reported; all were caused by serogroup C meningococci of ST-11. The highest incidence was observed among children under one year of age (15.71/100,000 in 2011). The general case fatality rate in the years 2010-2011 was 10.0%. Meningococci of serogroup B, C, Y and W-135 were responsible for 48.8%, 36.6%, 1.2% and 1.2% of cases, respectively. All isolates were susceptible to third generation cephalosporins, chloramphenicol, ciprofloxacin, and 84.2% were susceptible to penicillin. MLST analysis (2009-2011) revealed that among serogroup B isolates the most represented were clonal complexes (CC) ST-32CC, ST-18CC, ST-41/44CC, ST-213CC and ST-269CC, and among serogroup C: ST-103CC, ST-41/44CC and ST-11CC.The detection of IMD in Poland has changed over time, but observed increase in the incidence of the disease was mostly attributed to changes in the surveillance system including an expanded case definition and inclusion of data from non-culture diagnostics

Serogroup distribution of meningococci responsible for invasive infections in Poland, 2002–2011.

<p>(n = 1936; UNK - cases with unknown serogroup).</p

Molecular characterization of meningococcal isolates of serogroup B and C belonging to the most dominant clonal complexes (CC) represented at least by 10 isolates, 2009–2011.

a<p>ST – sequence type.</p