The lysin LysGH15, derived from the staphylococcal phage GH15, exhibits a wide lytic spectrum and highly efficient lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). Here, we found that LysGH15 did not induce resistance in MRSA or methicillin-sensitive S. aureus (MSSA) strains after repeated treatment. Although LysGH15 triggered the generation of LysGH15-specific antibodies in mice, these antibodies did not block lytic activity in vitro (nor the binding capacity of LysGH15). More importantly, when the antibody titre was highest in mice immunized with LysGH15, a single intravenous injection of LysGH15 was sufficient to protect mice against lethal infection with MRSA. These results indicated that LysGH15-specific antibodies did not affect the killing efficiency of LysGH15 against MRSA in vitro or in vivo. LysGH15 also reduced pro-inflammatory cytokines in mice with lethal infections. Furthermore, a high-dose LysGH15 injection did not cause significant adverse effects or pathological changes in the main organs of treated animals. These results provide further evidence for the administration of LysGH15 as an alternative strategy for the treatment of infections caused by MRSA.

Giardia infection is one of the most common causes of waterborne diarrheal disease in a wide array of mammalian hosts, including humans globally. Although numerous studies have indicated that adaptive immune responses are important for Giardia defense, however, whether the host innate immune system such as TLRs recognizes Giardia remains poorly understood. TLR2 plays a crucial role in pathogen recognition, innate immunity activation, and the eventual pathogen elimination. In this study, we investigated the role of TLR2 as a non-protective inflammatory response on controlling the severity of giardiasis. RT-PCR analysis suggested that TLR2 expression was increased in vitro. We demonstrated that Giardia lamblia-induced cytokines expression by the activation of p38 and ERK pathways via TLR2. Interestingly, the expression of IL-12 p40, TNF-α, and IL-6, but not IFN-γ, was enhanced in TLR2-blocked and TLR2−/− mouse macrophages exposed to G. lamblia trophozoites compared with wild-type (WT) mouse macrophages. Further analysis demonstrated that G. lamblia trophozoites reduced cytokines secretion by activating AKT pathway in WT mouse macrophages. Immunohistochemical staining in G. lamblia cysts infected TLR2−/− and WT mice showed that TLR2 was highly expressed in duodenum in infected WT mice. Also, infected TLR2−/− and AKT-blocked mice showed an increased production of IL-12 p40 and IFN-γ compared with infected WT mice at the early stage during infection. Interestingly, infected TLR2−/− and AKT-blocked mice displayed a decreased parasite burden, an increased weight gain rate, and short parasite persistence. Histological morphometry showed shortened villus length, hyperplastic crypt and decreased ratio of villus height/crypt depth in infected WT mice compared with in infected TLR2−/− and AKT-blocked mice. Together, our results suggested that TLR2 deficiency leads to alleviation of giardiasis and reduction of parasite burden through the promotion of proinflammatory cytokines production. For the first time, our results demonstrated that TLR2 played a negative role in host defense against Giardia.

In this work, structures, and properties of Cu(2+) and CuCl(+) hydrates in the gas and aqueous phases have been investigated using the B3LYP method. Contact ion pair (CIP) and solvent-shared ion pair (SSIP) were both taken into account for CuCl(+) hydrates. Our calculations show that [Cu(H(2)O)(n)](2+) clusters favor a very open four-coordinated structure for n = 5-12 in the gas phase, while a five-coordinated conformer is favored for n > or = 8 in the aqueous phase. An approximate complete solvation shell of Cu(2+) in the aqueous phase needs more than 12 water molecules, while that of CuCl(+) in the aqueous phase needs only about eight water molecules. For [CuCl(H(2)O)(n)](+) clusters, the most stable structure is a four-coordinated CIP conformer for n = 4-7 in the gas phase and a five-coordinated CIP conformer for n = 8-10 in the aqueous phase. However, the five-coordinated CIP/h conformer (CIP conformer that the axial chloride atom tends to dissociate) of [CuCl(H(2)O)(n)](+) clusters becomes more favorable as n increases to 11. As the hydration process proceeds, the charges on the copper atom of [Cu(H(2)O)(n)](2+) clusters decrease, while those of [CuCl(H(2)O)(n)](+) clusters increase (probably due to the dissociation of Cl(-)). The d-d electron transition and partial charge transition band around 160 nm of the five-coordinated conformer of [Cu(H(2)O)(n)](2+) clusters and those bands (approximately 170 and approximately 160 nm) of SSIP or five-coordinated CIP/h conformers of [CuCl(H(2)O)(n)](+) clusters are coincident with the absorption of [Cu](2+)(aq) species (approximately 180 nm) resolved from the spectra obtained in trace CuCl(2) (ca. 10(-5) mol x kg(-1)) + LiCl (0-18 mol x kg(-1)) aqueous solution, while those of five-coordinated CIP conformers of [CuCl(H(2)O)(n)](+) clusters (n = 8 and 9) around 261 and 247 nm correspond to the absorption of [CuCl](+)(aq) species (approximately 250 nm). Our calculated electronic spectra indicate that the typical peak of copper(II)-chloride complexes changes from 180 to 250 nm, and 275 nm, as the process of Cl(-) coordination. For [Cu](2+)(aq), [CuCl](+)(aq), and [CuCl(2)](0)(aq) species, the central Cu(II) atom prefers five-coordination.

Monolayer phosphorene has attracted much attention owing to its extraordinary electronic, optical, and structural properties. Rationally tuning the electrical transport characteristics of monolayer phosphorene is essential to its applications in electronic and optoelectronic devices. Herein, we study the electronic transport behaviors of monolayer phosphorene with surface charge transfer doping of electrophilic molecules, including 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), NO2, and MoO3, using density functional theory combined with the nonequilibrium Green's function formalism. F4TCNQ shows optimal performance in enhancing the p-type conductance of monolayer phosphorene. Static electronic properties indicate that the enhancement is originated from the charge transfer between adsorbed molecule and phosphorene layer. Dynamic transport behaviors demonstrate that additional channels for hole transport in host monolayer phosphorene were generated upon the adsorption of molecule. Our work unveils the great potential of surface charge transfer doping in tuning the electronic properties of monolayer phosphorene and is of significance to its application in high-performance devices.