Characterisation and sequencing of the novel phage Abp95, which is effective against multi-genotypes of carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii has become one of the most challenging conditional pathogens in health facilities. It causes various infectious diseases in humans, such as wound or urinary tract infections and pneumonia. Phage therapy has been used as an alternative strategy for antibiotic-resistant A. baumannii infections and has been approved by several governments. Previously, we have reported two potential phage therapy candidates, Abp1 and Abp9, both of which are narrow-host-range phages. In the present study, we screened and isolated 22 A. baumannii bacteriophages from hospital sewage water and determined that Abp95 has a wide host range (29%; 58/200). The biological and genomic characteristics and anti-infection potential of Abp95 were also investigated. Abp95 belongs to the Myoviridae family, with a G+C content of 37.85% and a genome size of 43,176 bp. Its genome encodes 77 putative genes, none of which are virulence, lysogeny, or antibiotic resistance genes. Abp95 was found to accelerate wound healing in a diabetic mouse wound infection model by clearing local infections of multidrug-resistant A. baumannii. In conclusion, the lytic phage Abp95, which has a wide host range, demonstrates potential as a candidate for phage therapy against multiple sequence types of carbapenem-resistant A. baumannii.

Structure and reactivity studies of the aluminum analogue of Piers' borane [HAl(C6F5)2]3.

The aluminum analogue of Piers' borane, [HAl(C6F5)2]31, is prepared on a gram-scale. Density functional theory (DFT) calculations reveal 1 has a higher fluoride ion affinity (FIA) than Piers' borane, while the Al-H moiety proved to be a strong hydride donor, reacting with alcohol and terminal alkyne to give the corresponding dehydrogenative products 3 and 4. Hydroalumination product 5 was prepared via reaction of 1 with aldehyde. In addition, 1 catalyzes the hydrosilylation of alkynes and alkenes.

Ambiphilic Behavior of Ge(II)-Pseudohalides in Inter- and Intramolecular Frustrated Lewis Pair Alkyne Addition Reactions.

The reaction of the germylene chloride (NacNac)GeCl (1, NacNac = CH{(CMe)(2,6-iPr2C6H3N)}2), phenylacetylene, and B(C6F5)3 gives the intermolecular frustrated Lewis pair (FLP) addition product 2. In this case, the Ge(II) center acts as a base. In contrast, the analogous reaction of germylene thiocyanate 3 reacts independently with B(C6F5)3 to give the germylene cation salt [(NacNac)Ge][SCNB(C6F5)3] 4. Subsequent in the presence of alkynes, the Ge(II) cation and γ-C of 4 act as a Lewis acidic and basic center, respectively, to affect the addition of alkynes, affording products [(NacNac)Ge(RCCR')][SCNB(C6F5)3] 5 and 6. Compound 4 also reacts with Me3SiCN to give the cyanide-bridged Ge/B species 7, which also reacts with phenylacetylene to give CN abstraction and intramolecular addition yielding the salt [(NacNac)Ge(PhCCH)][NCB(C6F5)3] 8. Despite the similarity of 1 and 3, DFT calculations show that the highest occupied molecular orbital (HOMO) of 1 is mainly located at the more sterically hindered germylene center, while the HOMO of 3 is located on the less sterically hindered NCS group, prompting markedly different FLP addition products.

The Varied Frustrated Lewis Pair Reactivity of the Germylene Phosphaketene (CH{(CMe)(2,6-i Pr2 C6 H3 N)}2 )GePCO.

The germylene species (CH{(CMe)(2,6-iPr2 C6 H3 N)}2 )GePCO 1 is shown to react with the Lewis acids (E(C6 F5 )3 E=B, Al). Nonetheless, 1 participates in FLP chemistry with electron deficient alkynes or olefins, acting as an intramolecular FLP. In contrast, in the presence of B(C6 F5 )3 and an electron rich alkyne, 1 behaves as Ge-based nucleophile to effect intermolecular FLP addition to the alkyne. This reactivity demonstrates that the reaction pathway is controlled by the nature of the electrophile and nucleophile generated in solution, as revealed by extensive DFT calculations.

Corrigendum: Isolation and Characterization of a Novel Myophage Abp9 Against Pandrug Resistant Acinetobacater baumannii.

[This corrects the article DOI: 10.3389/fmicb.2020.506068.].

Isolation and Characterization of a Novel Myophage Abp9 Against Pandrug Resistant Acinetobacater baumannii.

Acinetobacter baumannii (A. baumannii) has emerged as one of the most troublesome pathogens in health care institutions. A. baumannii can cause a wide range of diseases in humans, including pneumonia and septicemia. Phage therapy has drawn great interest from medical researchers as a potential way to control infections by antibiotic-resistant A. baumannii. Using a pandrug-resistant clinical A. baumannii isolate ABZY9 as an indicator, we isolated a lytic phage Abp9 from hospital sewage. Abp9 belongs to myoviridae family and shows a wider host range of 12%. Abp9 contains a linear double-stranded DNA genome of 44,820 bp with a G + C content of 37.69%. The Abp9 genome contains 80 open reading frames, but lacks any known virulence genes or lysogen-formation genes. In a systemic A. baumannii infection mouse models, Abp9 treatment showed good therapeutic effects. We have also observed an excellent lytic activity against A. baumannii in biofilm form of growth in vitro. All of these suggest that Abp9 is a good candidate for the phage therapy against drug-resistant A. baumannii infections.

A Carrier-Free Nanostructure Based on Platinum(IV) Prodrug Enhances Cellular Uptake and Cytotoxicity.

Flurbiprofen, a hydrophobic COX inhibitor, was coordinated axially with oxoplatin to form a new conjugate, cis, cis, trans-[Pt(IV)(NH3)2Cl2(flurbiprofen)2]. The successful synthesis of this new conjugate was confirmed by 1H, 13C, and 195Pt NMR. The potential of this conjugate being reduced to cisplatin and subsequently exerting its DNA cross-linking ability was verified using cyclic voltammetry (CV), HPLC, and mass spectrometry (MS). This conjugate showed markedly higher cytotoxicity on many cancer cell lines than cisplatin, flurbiprofen, and their physical mixture (mole ratio, cisplatin:flurbiprofen = 1:2). This is consistent with the result of an apoptosis-inducing assay. This conjugate spontaneously assembles carrier-free nanoparticles in aqueous solution, which is confirmed by DLS, TEM, SEM, and AFM, and thus facilitates cellular uptake and markedly improves its cytotoxicity and apoptosis-inducing ability in vitro.

Overcoming resistance to cisplatin by inhibition of glutathione S-transferases (GSTs) with ethacraplatin micelles in vitro and in vivo.

Platinum-based DNA-adducting agents are used extensively in the clinic for cancer chemotherapy. However, the anti-tumor efficacy of these drugs is severely limited by cisplatin resistance, and this can lead to the failure of chemotherapy. One of cisplatin resistance mechanisms is associated with overexpression of glutathione S-transferases (GSTs), which would accelerate the deactivation of cisplatin and decrease its antitumor efficiency. Nanoscale micelles encapsulating ethacraplatin, a conjugate of cisplatin and ethacrynic acid (an effective GSTs inhibitor), can enhance the accumulation of active cisplatin in cancer cells by inhibiting the activity of GSTs and circumventing deactivation of cisplatin. In vitro and in vivo results provide strong evidence that GSTs inhibitor-modified cisplatin prodrug combined with nanoparticle encapsulation favor high effective platinum accumulation, significantly enhanced antitumor efficacy against cisplatin-resistant cancer and decreased system toxicity. It is believed that these ethacraplatin-loaded micelles have the ability of overcoming resistance of cancers toward cisplatin and will improve the prospects for chemotherapy of cisplatin-resistant cancers in the near future.