Networking the way towards antimicrobial combination therapies

Publicado em "8th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB 2014)"The exploration of new antimicrobial combinations is a pressing concern for Clinical Microbiology due to the growing number of resistant strains emerging in healthcare settings and in the general community. Researchers are screening agents with alternative modes of action and interest is rising for the potential of antimicrobial peptides (AMPs). This work presents the first ever network reconstruction of AMP combinations reported in the literature fighting Pseudomonas aeruginosa infections. The network, containing 193 combinations of AMPs with 39 AMPs and 154 traditional antibiotics, is expected to help in the design of new studies, notably by unveiling different mechanisms of action and helping in the prediction of new combinations and synergisms. The challenges faced in the attempted text-mining approaches and other considerations regarding the manual curation of the data are pointed out, reflecting about the future automation of this type of reconstruction as means to widen the scope of analysis

Characterization of staphylococcal cassette chromosome mec elements from methicillin-resistant Staphylococcus pseudintermedius infections in Australian animals

We examined the oxacillin resistance phenotype and genomic structure of staphylococcal cassette chromosome mec (SCCmec) elements from 77 veterinary methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates. Isolates were characterized by oxacillin broth microdilution, whole-genome sequencing, and bioformatics analysis. Five previously described SCCmec elements, and a sixth novel element, were identified: SCCmec III (also known as II-III), ΨSCCmec57395, and SCCmecNA45 (a SCCmec VII variant), all previously described in MRSP, and SCCmec IVg and SCCmec VT, previously described in both methicillin-resistant Staphylococcus aureus (MRSA) and MRSP. The sixth element was novel and found among nine geographically clustered isolates. This novel pseudostaphylococcal cassette chromosome (ΨSCCmecKW21) contained a class A mec gene complex but lacked ccr genes. It also harbored heavy metal (cadmium) resistance determinants. The median oxacillin MIC values among ΨSCCmecKW21, SCCmec III, and SCCmec VT isolates were significantly higher than those determined for the SCCmecNA45 VII variant isolates and ΨSCCmec57395 and SCCmec IVg isolates. ΨSCCmecKW21 was found exclusively in sequence type 497 (ST497), an MRSP clone that is locally successful in Victoria, Australia. Future studies are necessary to determine if this clone has disseminated further afield and if ΨSCCmecKW21 has moved into other MRSP lineages or staphylococcal species. IMPORTANCE Staphylococcus pseudintermedius is a significant veterinary pathogen and occasional cause of infections in humans. β-Lactams are an important group of antimicrobials used to treat staphylococcal infections in humans and animals. However, when staphylococci become methicillin resistant via the acquisition of a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec), they become resistant to all β-lactams. This study detected a novel SCCmec element among a cluster of methicillin-resistant S. pseudintermedius isolates from animals in Australia. It also detected SCCmec elements in S. pseudintermedius that had high similarity to those identified in methicillin-resistant Staphylococcus aureus, demonstrating how human and animal pathogens can share the same resistance determinants

Genomic Deletion Marking an Emerging Subclone of Francisella tularensis subsp. holarctica in France and the Iberian Peninsula

P. 7465-7470Francisella tularensis subsp. holarctica is widely disseminated in North America and the boreal and temperate regions of the Eurasian continent. Comparative genomic analyses identified a 1.59-kb genomic deletion specific to F. tularensis subsp. holarctica isolates from Spain and France. Phylogenetic analysis of strains carrying this deletion by multiple-locus variable-number tandem repeat analysis showed that the strains comprise a highly related set of genotypes, implying that these strains were recently introduced or recently emerged by clonal expansion in France and the Iberian PeninsulaS

DNA Sequence Analysis of Regions Surrounding \u3ci\u3ebla\u3c/i\u3e\u3csub\u3eCMY-2\u3c/sub\u3e from Multiple \u3ci\u3eSalmonella\u3c/i\u3e Plasmid Backbones

The emergence in the United States of resistance to expanded-spectrum cephalosporin (e.g., ceftriaxone) within the salmonellae has been associated primarily with three large (\u3e100-kb) plasmids (designated types A, B, and C) and one 10.1-kb plasmid (type D) that carry the blaCMY-2 gene. In the present study, the distribution of these four known blaCMY-2-carrying plasmids among 35 ceftriaxone-resistant Salmonella isolates obtained from 1998 to 2001 was examined. Twenty-three of these isolates were Salmonella enterica serotype Newport, 10 were Salmonella enterica serotype Typhimurium, 1 was Salmonella enterica serotype Agona, and 1 was Salmonella enterica serotype Reading. All 23 serotype Newport isolates carried a type C plasmid, and 5, 4, and 1 serovar Typhimurium isolate carried type B, A, and C plasmids, respectively. Both the serotype Agona and serotype Reading isolates carried type A plasmids. None of the isolates carried a type D plasmid. Hybridization data suggested that plasmid types A and C were highly related replicons. DNA sequencing revealed that the region surrounding blaCMY-2 was highly conserved in all three plasmid types analyzed (types B, C, and D) and was related to a region surrounding blaCMY-5 from the Klebsiella oxytoca plasmid pTKH11. These findings are consistent with a model in which blaCMY-2 has been disseminated primarily through plasmid transfer, and not by mobilization of the gene itself, to multiple Salmonella chromosomal backbones