Pseudomonas aeruginosa is one of the most widespread and troublesome opportunistic pathogens that is capable of colonizing various human tissues and organs and is often resistant to many currently used antibiotics. This resistance is caused by different factors, including the acquisition of specific resistance genes, intrinsic capability to diminish antibiotic penetration into the bacterial cell, and the ability to form biofilms. This situation has prompted the development of novel compounds differing in their mechanism of action from traditional antibiotics that suppress the growth of microorganisms or directly kill bacteria. Instead, these new compounds should decrease the pathogens’ ability to colonize and damage human tissues by inhibiting the virulence factors and biofilm formation. The lectins LecA and LecB that bind galactose and fucose, as well as oligo- and polysaccharides containing these sugars, are among the most thoroughly-studied targets for such novel antibacterials. In this review, we summarize the results of experiments highlighting the importance of these proteins for P. aeruginosa pathogenicity and provide information on existing lectins inhibitors and their effectiveness in various experimental models. Particular attention is paid to the effects of lectins inhibition in animal models of infection and in clinical practice. We argue that lectins inhibition is a perspective approach to combating P. aeruginosa. However, despite the existence of highly effective in vitro inhibitors, further experiments are required in order to advance these inhibitors into pre-clinical studies.

Listeria monocytogenes is a causative agent of foodborne infection in humans and animals. The virulence factor InlB interacts with mammalian receptor c-Met via its internalin domain to provide L. monocytogenes invasion in non-professional phagocytes. Naturally occurring InlB internalin domain variants form four subclusters on the maximal likelihood tree. Four variants belonging to distinct subclusters were cloned into the vector carrying 3΄ and 5΄-flanking sequences to restore full length inlB and expressed in the L. monocytogenes strain EGDeΔinlB. The substitutions Val132Ile, Thr117Ala and Ile138Leu, Thr251Met/Ser were specific for variants 13, 14 and 1, respectively, the variant 9 carried Ser73Asn, Ile91Val, Leu164Pro, Met251Ser/Thr substitutions. All InlB variants improved invasion of the parental strain in murine colon carcinoma C26 cells with 4.6-fold difference between the most and least effective variants (variants 14 and 13, respectively, P < 0.05). Bacterial loads in livers of intragastrically infected mice were 258, 149 and 92 times higher for variant 14, 13 and 1 carrying strains, respectively, than for EGDeΔinlB (P < 0.01). In contrast, the variant 9 did not noticeably improve infection comparatively to the parental strain. Overall, obtained results demonstrated that naturally occurred InlB internalin domain variants differed in their ability to support intragastric infection in mice.

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BackgroundMany algorithms and programs are available for phylogenetic reconstruction of families of proteins. Methods used widely at present use either a number of distance-based principles or character-based principles of maximum parsimony or maximum likelihood.ResultsWe developed a novel program, named PQ, for reconstructing protein and nucleic acid phylogenies following a new character-based principle. Being tested on natural sequences PQ improves upon the results of maximum parsimony and maximum likelihood. Working with alignments of 10 and 15 sequences, it also outperforms the FastME program, which is based on one of the distance-based principles. Among all tested programs PQ is proved to be the least susceptible to long branch attraction. FastME outperforms PQ when processing alignments of 45 sequences, however. We confirm a recent result that on natural sequences FastME outperforms maximum parsimony and maximum likelihood. At the same time, both PQ and FastME are inferior to maximum parsimony and maximum likelihood on simulated sequences. PQ is open source and available to the public via an online interface.ConclusionsThe software we developed offers an open-source alternative for phylogenetic reconstruction for relatively small sets of proteins and nucleic acids, with up to a few tens of sequences.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2399-4) contains supplementary material, which is available to authorized users.