Discovery, characterization and in vivo activity of pyocin SD2, a protein antibiotic from Pseudomonas aeruginosa

Increasing rates of antibiotic resistance among Gram-negative pathogens such as Pseudomonas aeruginosa means alternative approaches to antibiotic development are urgently required. Pyocins, produced by P. aeruginosa for intraspecies competition, are highly potent protein antibiotics known to actively translocate across the outer membrane of P. aeruginosa. Understanding and exploiting the mechanisms by which pyocins target, penetrate and kill P. aeruginosa is a promising approach to antibiotic development. In this work we show the therapeutic potential of a newly identified tRNase pyocin, pyocin SD2, by demonstrating its activity in vivo in a murine model of P. aeruginosa lung infection. In addition, we propose a mechanism of cell targeting and translocation for pyocin SD2 across the P. aeruginosa outer membrane. Pyocin SD2 is concentrated at the cell surface, via binding to the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide (LPS), from where it can efficiently locate its outer membrane receptor FpvAI. This strategy of utilizing both the CPA and a protein receptor for cell targeting is common among pyocins as we show that pyocins S2, S5 and SD3 also bind to the CPA. Additional data indicate a key role for an unstructured N-terminal region of pyocin SD2 in the subsequent translocation of the pyocin into the cell. These results greatly improve our understanding of how pyocins target and translocate across the outer membrane of P. aeruginosa. This knowledge could be useful for the development of novel anti-pseudomonal therapeutics and will also support the development of pyocin SD2 as a therapeutic in its own right

Efficient Mapping of Interdependent Scans

. Distributed memory multiprocessors are extremely sensitive to communication costs. Some global communications such as scans and reductions are of special interest since their cost is much lower than for point to point communications. Our paper focuses on an algorithm which efficiently takes the mapping of scans into account. 1 Introduction Communications remain the most critical aspect of performance in efficiently programming distributed memory multiprocessors. Hence minimizing communications is an indispensable task. A static placement may be obtained in two different ways: one may ask the user to insert annotations to specify data mapping `a la HPF. Our approach is to leave this work to the compiler (see 2). However such a placement will not be sufficient if some particularities of the target machine are not taken into account, for instance if communication primitives with low overhead are not used. In this paper we propose a method to compute a placement which efficiently exploi..