Rescuing tetracycline class antibiotics for the treatment of multidrug-resistant Acinetobacter baumannii pulmonary infection

Acinetobacter baumannii causes high mortality in ventilator-associated pneumonia patients, and antibiotic treatment is compromised by multidrug-resistant strains resistant to β-lactams, carbapenems, cephalosporins, polymyxins, and tetracyclines. Among COVID-19 patients receiving ventilator support, a multidrug-resistant A. baumannii secondary infection is associated with a 2-fold increase in mortality. Here, we investigated the use of the 8-hydroxyquinoline ionophore PBT2 to break the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multidrug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. PBT2 and zinc disrupted metal ion homeostasis in A. baumannii, increasing cellular zinc and copper while decreasing magnesium accumulation. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multidrug-resistant A. baumannii infections. Importance: Within intensive care unit settings, multidrug-resistant (MDR) Acinetobacter baumannii is a major cause of ventilator-associated pneumonia, and hospital-associated outbreaks are becoming increasingly widespread. Antibiotic treatment of A. baumannii infection is often compromised by MDR strains resistant to last-resort β-lactam (e.g., carbapenems), polymyxin, and tetracycline class antibiotics. During the on-going COVID-19 pandemic, secondary bacterial infection by A. baumannii has been associated with a 2-fold increase in COVID-19-related mortality. With a rise in antibiotic resistance and a reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. Rescuing the efficacy of existing therapies for the treatment of MDR A. baumannii infection represents a financially viable pathway, reducing time, cost, and risk associated with drug innovation.David M.P. De Oliveira, Brian M. Forde, Minh-Duy Phan, Bernhard Steiner, Bing Zhang, Johannes Zuegg, Ibrahim M. El-deeb, Gen Li, Nadia Keller, Stephan Brouwer, Nichaela Harbison-Price, Amanda J. Cork, Michelle J. Bauer, Saleh F. Alquethamy, Scott A. Beatson, Jason A. Roberts, David L. Paterson, Alastair G. McEwan, Mark A.T. Blaskovich, Mark A. Schembri, Christopher A. McDevitt, Mark von Itzstein, Mark J. Walke

GIZA 11 AND GIZA 12; TWO NEW FLAX DUAL PURPOSE TYPE VARIETIES

Sixteen flax genotypes {13 promising lines and 3 check varieties viz., Giza 8 (oil type), Sakha 1 (dual purpose type) and Sakha 3 (fiber type)} were evaluated for straw, seed, oil yields and their related traits under twelve different environments; four locations (Sakha, Etay El-Baroud, Ismailia and Giza Exp. Stations through three successive seasons (2011/12, 2012/13 and 2013/14). These materials were evaluated in a randomized complete blocks design with three replications at the twelve above-mentioned environments. The analysis of variance revealed highly significant differences among genotypes (G), environments (E) and G x E interaction for all studied traits except straw weight per plant, indicating a wide range of variation among genotypes, environments and these genotypes exhibited differential response to environmental conditions. The significant variance due to residual for all characters except both straw weight per plant and oil yield per fad indicated that genotypes differed with respect to their stability suggesting that prediction would be difficult, which means that mean performance alone would not be appropriate. Interaction component of variance (σ2ge) was less than the genotypic variance (σ2g) for all characters, indicating that genotypes differ in their genetic potential for these traits. This was reflected in high heritability and low discrepancy between phenotypic (PCV) and genotypic (GCV) coefficients of variability values for these traits indicating the possibility of using each of long fiber percentage, plant height and technical stem length as selection indices for improving straw weight per plant, as well as, using 1000-seed weight and capsules number per plant as selection indices for improving seed weight per plant. Yield stability (YSi) statistic indicated that S.541-C/3 and S.541-D/10 gave high mean performance and stability for straw, fiber, seed and oil yields per fad in addition to oil percentage, capsules number per plant and 1000-seed weight. Therefore, the two genotypes well be released under the name Giza 11 and Giza 12, respectively. These newly released varieties are of dual purpose type for straw, fiber, seed and oil yield. They may replace the low yielding cultivars Giza 8, Sakha 1 and Sakha 3

Susceptibilidade de larvas de Cerotoma arcuata Olivier (Coleoptera: Chrysomelidae) a Beauveria bassiana (Bals.) Vuillemin, Metarhizium anisopliae (Metsch.) Sorokin e Bacillus thuringiensis Berliner Susceptibility of Cerotoma arcuata Olivier (Coleoptera: Chrysomelidae) larvae to Beauveria bassiana (Bals.) Vuillemin, Metarhizium anisopliae (Metsch.) Sorokin and Bacillus thuringiensis Berliner

Larvas de 2&deg; instar de Cerotoma arcuata foram avaliadas em relação à susceptibilidade aos fungos entomopatogênicos Beauveria bassiana, Metarhizium anisopliae e a bactéria Bacillus thuringiensis com as toxinas Cry3. Os insetos adultos foram mantidos em gaiolas e alimentados com plântulas de feijão (Phaseolus vulgaris L.) e as larvas em "gerbox" com cotilédones de plântulas de feijão recém-germinadas. Das oito estirpes de B. bassiana avaliadas, CG 156 e CG 213 causaram 100% de mortalidade das larvas, as duas estirpes de M. anisopliae CG 210 e CG 321 foram patogênicas, eliminando 80 e 100% das larvas de C. arcuata, e, das cinco estirpes de B. thuringiensis testadas, o isolado CG 940 causou 70% de mortalidade das larvas.<br>Second instar larvae of Cerotoma arcuata were evaluated concerning the susceptibility to fungi Beauveria bassiana and Metarhizium anisopliae and Bacillus thuringiensis strains containing Cry3 toxin. Adults of C. arcuata were kept in large cages and fed on bean seedlings and the larvae were reared in ‘gearbox’ feeding on germinated Phaseolus bean cotyledons. Strains CG 156 and CG 213 of B. bassiana killed 100% of the insect larvae and strains CG 210 and CG 321 of M. anisopliae killed 80 and 100% of the insect larvae. Strain CG 940 of B. thuringiensis killed 70% of the insect larvae