Modelling of a seasonally perturbed competitive three species impulsive system.

The population of biological species in the ecosystem is known sensitive to the periodic fluctuations of seasonal change, food resources and climatic conditions. Research in the ecological management discipline conventionally models the behavior of such dynamic systems through specific impulsive response functions, but the results of such research are applicable only when the environments conform exactly to the conditions as defined by the specific response functions that have been implemented for specific scenarios. This means that the application of previous work may be somewhat limited. Moreover, the intra and inter competitions among species have been seldom studied for modelling the prey-predator ecosystem. To fill in the gaps this paper models the delicate balance of two-prey and one-predator system by addressing three main areas of: ⅰ) instead of using the specific impulse response this work models the ecosystem through a more general response function; ⅱ) to include the effects due to the competition between species and ⅲ) the system is subjected to the influences of seasonal factors. The seasonal factor has been implemented here in terms of periodic functions to represent the growth rates of predators. The sufficient condition for the local and global asymptotic stability of the prey-free periodic solution and the permanence of the system have been subsequently obtained by using the Comparison techniques and the Floquet theorems. Finally, the correctness of developed theories is verified by numerical simulation, and the corresponding biological explanation is given.

TLR2 agonist Pam3CSK4 enhances the antibacterial functions of GM-CSF induced neutrophils to methicillin-resistant Staphylococcus aureus.

A proliferation of studies have demonstrated that the toll-like receptor 2 (TLR2) pathway affects the chemotaxis, phagocytosis, and cytokine release of neutrophils when pathogens invade. Our previous studies have demonstrated that pretreatment with high doses of Pam3CSK4 (>25 µg/ml) improves the antimicrobial activity of neutrophils, however, short-lived neutrophils limit their therapeutic functions. Here, we used granulocyte macrophage-colony stimulating factor (GM-CSF) to generate neutrophils from murine bone marrow, and assessed their effect on the immune response against methicillin-resistant Staphylococcus aureus. As comparing with classical method of generating neutrophils directly from murine bone marrow, our findings show that pretreatment with Pam3CSK4 enhanced the phagocytic and killing activities against MRSA by the GM-CSF induced neutrophils (GM-CSF neutrophils). Chemotaxis of GM-CSF induced neutrophils was significantly increased after the pretreatment with Pam3CSK4. Furthermore, Pam3CSK4 pretreatment enhanced iNOS, CRAMP, TNF-α, IL-1ß, IL-10, and IL-6 expression. Finally, we observed that p38MAPK and Akt phosphorylation kinases were increased significantly in GM-CSF neutrophils pretreatment with Pam3CSK4 in a dose- and time-dependent manner, whereas p38MAPK inhibitor (SB2021190) and PI3K inhibitor (LY294002) attenuated the antimicrobial activities including phagocytosis, killing activity, respiratory burst, and the release of lactoferrin(LTF) by the GM-CSF induced neutrophils. Together, these findings suggest that pretreatment with Pam3CSK4 enhances the antibacterial function of GM-CSF neutrophils against MRSA, and this could be related to the p38MAPK and PI3K signaling pathways.

Outbreak by Ventilator-Associated ST11 K. pneumoniae with Co-production of CTX-M-24 and KPC-2 in a SICU of a Tertiary Teaching Hospital in Central China.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) often responsible for numerous hospital-associated outbreaks has become an important public health problem. From January 2013 to February 2014, a total of 41 non-duplicate K. pneumoniae isolates with carbapenem resistance, were collected at a tertiary teaching hospital in Nanchang, central China. Among 41 K. pneumoniae isolates, 28 were isolated from hospitalized patients including 19 from the patients in surgery intensive care unit (SICU) and 13 were isolated from ventilators. Twenty-four of 28 patients infected by CRKP have been submitted to mechanical ventilation using ventilator. More than 95% of the CRKP isolates were resistant to 13 antimicrobials tested. All CRKP isolates were confirmed as carbapenemase producer and were positive for bla KPC-2, with one positive for both blaKPC-2 and bla NDM-1. All carbapenemase-producing isolates harbored at least one of extended spectrum ß-lactamase genes tested, among which 95.1% (39/41) of the tested isolates were found to harbor both bla CTX-M-24 and bla KPC-2, Of note, one isolate harbored simultaneously two carbapenemase genes (bla KPC-2 and bla NDM-1) and two ESBL genes (bla CTX-M-3 and bla TEM-104). To the best of our knowledge, coexistence of bla KPC-2 and bla CTX-M-24 in one isolate is first reported. MLST results showed that 41 CRKP isolates belonged to four sequence types (STs) including ST11, novel ST1854, novel ST1855, and ST1224. PFGE results displayed three PFGE clusters. Thirty-eight ST11 CRKP isolates (92.7%, 38/41) including all 13 isolates from ventilators and 25 isolates from patients from seven wards (18 from SICU) belonged to same PFGE cluster, indicating these isolates were clonally related. Fifteen isolates have an identical undistinguished pattern (100% similarity) forming a single clonal population. Moreover, this clone was exclusively linked to the cases attended in SICU and linked to the Ventilators. Additionally, the other SICU cases were linked to closely related clones (similarity greater than 95%). These data indicated that the occurrence of a clonal outbreak associated with ventilators has been found. In conclusion, outbreak by ventilator-associated ST11 K. pneumoniae with co-production of CTX-M-24 and KPC-2 is found in a SICU of a tertiary teaching hospital in central China.

[Protective effect of pretreatment with TLR2 agonist Pam3Csk4 on mice challenged by methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To evaluate the protective effect of pretreatment with Pam3Csk4, a Toll-like receptor 2 (TLR2) agonist, on mice against methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: Kunming mice were injected with Pam3Csk4 (25, 50, 100 µg/mice) via tail vein. 12 and 24 hours later, the mice were inoculated with live MRSA (7×10(10) CFU/kg, ATCC43300) via tail vein. All mice were observed at 2-hour intervals for the first 24 hours and 6-hour intervals for the rest time, and survival was monitored for at least 7 days. Bacterial burden in liver, spleen and kidney of the mice were estimated by colony counting on nutrient agar 6 hours after infection (3×10(8) CFU/mice, ATCC43300). In addition, 6, 12 and 24 hours after MRSA challenge, the concentrations of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon γ (IFN-γ) and IL-10 were measured by ELISA, and the mRNA levels of these cytokines were detected by fluorescence quantitative PCR (qPCR). Finally, 24 hours after being pretreated with Pam3Csk4, mRNA levels of CXC chemokine ligand 1 (CXCL1) and Fcγ receptor III (FcγRIII) in spleen of the mice were evaluated by qPCR. RESULTS: Compared with normal saline-pretreated mice, we found that mice pretreated with the Pam3Csk4 (100 µg/mice) had higher survival in sepsis models caused by MRSA in dose- and time-dependent manners, and Pam3Csk4 (over 50 µg/mice)-pretreated mice had a survival rate more than 70%. In addition, the protein and mRNA levels of TNFα were markedly reduced in Pam3Csk4-pretreated mice at 6 and 12 hours, but not different from the controls at 24 hours post-infection. While IL-6 at protein and mRNA levels decreased in Pam3Csk4-pretreated mice only at 6 hours post-infection. Both protein and mRNA levels of IFN-γ greatly decreased in Pam3Csk4-pretreated mice compared with those of the control group. However, IL-10 level was unchanged between the two groups at all time points. Further studies showed that the mRNA levels of CXCL1 and FcγRIII were notably raised in spleen of the mice 24 hours after administered with Pam3Csk4 compared with normal saline-pretreated mice. CONCLUSION: Our results suggest that Pam3Csk4 pretreatment can protect mice from challenged by MRSA.

Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.

The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1ß and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-ß, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.

CREB, another culprit for TIGAR promoter activity and expression.

Cellular expression of the TP53-induced glycolysis and apoptosis regulator (TIGAR) protein results in the down-regulation of glycolysis, reduction of intracellular levels of reactive oxygen species, and protection from apoptosis. However, despite its biological importance, the mechanisms that regulate its expression remain obscure. The bioinformatic analysis performed in this study indicates that the TIGAR promoter region is highly conserved among species. Further analysis using 5'-deletion analysis and site-directed mutagenesis demonstrated that the region at -4/+13 contained a cAMP-response element (CRE). EMSA and chromatin immunoprecipitation showed that the site was recognized by CRE-binding protein (CREB). Furthermore, knockdown of CREB substantially reduced promoter activity and TIGAR expression in cells. In addition, over-expression of either CREB or forskolin enhanced promoter activity and TIGAR expression. These results provide evidence that CREB regulates TIGAR expression via a CRE-binding site at the TIGAR promoter.