Trindade dos Santos, M. | Search bioRxiv

bioRxiv2019

Comparative genome analysis of a multidrug-resistant Pseudomonas aeruginosa sequence type 277 clone that harbours two copies of the blaSPM-1 gene and multiple single nucleotide polymorphisms in other resistance-associated genes

Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of blaSPM-1 gene, encoding a metallo-beta-lactamase, in addition to other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify physiological key aspects that may lead to the exposure of new targets for therapy. This study was designed to characterize the genome of Pseudomonas aeruginosa CCBH4851 through the detection of genomic features and genome comparison with other Pseudomonas aeruginosa strains. The CCBH4851 closed genome showed features that were consistent with data reported for the specie. However, comparative genomics revealed the absence of genes important for pathogenesis. On the other hand, CCBH4851 genome contained acquired genomic islands that carry additional virulence and antimicrobial resistance-related genes. The presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations could influence the multidrug-resistant behavior of CCBH4851. Overall, the characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed several features that could directly impact the profile of virulence and antibiotic resistance of this pathogen in infectious outbreaks.

genomics↗

bioRxiv2019

Gene regulatory network inference and analysis of multidrug-resistant Pseudomonas aeruginosa

BackgroundHealthcare-associated infections caused by bacteria such as Pseudomonas aeruginosa are a major public health problem worldwide. Gene regulatory networks computationally represent interactions among regulatory genes and their targets, an important approach to understand bacterial behavior and to provide novel ways of overcoming scientific challenges, including the identification of potential therapeutic targets and the development of new drugs.\n\nObjectivesOur goal in this manuscript is to present a reconstruction of multidrug-resistant P. aeruginosa gene regulatory network and to analyze its topological properties.\n\nMethodsThe methodology was based on gene orthology inference by the reciprocal best hit method. We used the genome of P. aeruginosa CCBH4851 as the basis of the reconstruction process. This multidrug-resistant strain is representative of an endemic outbreak in Brazilian territory belonging to ST277.\n\nFindingsAs the main finding, we obtained a network with a larger number of regulatory genes, target genes and interactions compared to previous work. Topological analysis results are accordant to the complex network representation of biological processes.\n\nMain conclusionsThe network properties are consistent with P. aeruginosa biological features. To the best of our knowledge, the P. aeruginosa gene regulatory network presented here is the most complete version available to date.

systems biology↗