Dataset Information

Comparative Genomics Analysis of Plasmid pPV989-94 from a Clinical Isolate of Pantoea vagans PV989.

ABSTRACT: Pantoea vagans, a gram-negative bacterium from the genus Pantoea and family Enterobacteriaceae, is present in various natural environments and considered to be plant endophytes. We isolated the Pantoea vagans PV989 strain from the clinic and sequenced its whole genome. Besides a chromosome DNA molecule, it also harboured three large plasmids. A comparative genomics analysis was performed for the smallest plasmid, pPV989-94. It can be divided into four regions, including three conservative regions related to replication (R1), transfer conjugation (R2), and transfer leading (R3), and one variable region (R4). Further analysis showed that pPV989-94 is most similar to plasmids LA637P2 and pEA68 of Erwinia amylovora strains isolated from fruit trees. These three plasmids share three conservative regions (R1, R2, and R3). Interestingly, a fragment (R4') in R4, mediated by phage integrase and phage integrase family site-specific recombinase and encoding 9 genes related to glycometabolism, resistance, and DNA repair, was unique in pPV989-94. Homologues of R4' were found in other plasmids or chromosomes, suggesting that horizontal gene transfer (HGT) occurred among different bacteria of various species or genera. The acquired functional genes may play important roles in the adaptation of bacteria to different hosts or environmental conditions.

SUBMITTER: Xu L

PROVIDER: S-EPMC5971314 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative Genomics Analysis of Plasmid pPV989-94 from a Clinical Isolate of Pantoea vagans PV989.

Xu Lei L Yin Min M Zhu Tingyuan T Liu Yabo Y Ying Yuanyuan Y Lu Junwan J Lin Chaoqing C Ying Jianchao J Xu Teng T Ni Liyan L Bao Qiyu Q Lu Shunfei S

International journal of genomics 20180510

Pantoea vagans, a gram-negative bacterium from the genus Pantoea and family Enterobacteriaceae, is present in various natural environments and considered to be plant endophytes. We isolated the Pantoea vagans PV989 strain from the clinic and sequenced its whole genome. Besides a chromosome DNA molecule, it also harboured three large plasmids. A comparative genomics analysis was performed for the smallest plasmid, pPV989-94. It can be divided into four regions, includi ...[more]

PMID: 29862249

Similar Datasets

Project description:Nitrofurantoin is a commonly used chemotherapeutic agent in the treatment of uncomplicated urinary tract infections caused by the problematic multidrug resistant Gram-negative pathogen Klebsiella pneumoniae. The present study aims to elucidate the mechanism of nitrofurantoin action and high-level resistance in K. pneumoniae using whole-genome sequencing (WGS), qPCR analysis, mutation structural modeling and untargeted metabolomic analysis. WGS profiling of evolved highly resistant mutants (nitrofurantoin minimum inhibitory concentrations > 256 mg/L) revealed modified expression of several genes related to membrane transport (porin ompK36 and efflux pump regulator oqxR) and nitroreductase activity (ribC and nfsB, involved in nitrofurantoin reduction). Untargeted metabolomics analysis of total metabolites extracted at 1 and 4 h post-nitrofurantoin treatment revealed that exposure to the drug caused a delayed effect on the metabolome which was most pronounced after 4 h. Pathway enrichment analysis illustrated that several complex interrelated metabolic pathways related to nitrofurantoin bacterial killing (aminoacyl-tRNA biosynthesis, purine metabolism, central carbohydrate metabolism, and pantothenate and CoA biosynthesis) and the development of nitrofurantoin resistance (riboflavin metabolism) were significantly perturbed. This study highlights for the first time the key role of efflux pump regulator oqxR in nitrofurantoin resistance and reveals global metabolome perturbations in response to nitrofurantoin, in K. pneumoniae.IMPORTANCEA quest for novel antibiotics and revitalizing older ones (such as nitrofurantoin) for treatment of difficult-to-treat Gram-negative bacterial infections has become increasingly popular. The precise antibacterial activity of nitrofurantoin is still not fully understood. Furthermore, although the prevalence of nitrofurantoin resistance remains low currently, the drug's fast-growing consumption worldwide highlights the need to comprehend the emerging resistance mechanisms. Here, we used multidisciplinary techniques to discern the exact mechanism of nitrofurantoin action and high-level resistance in Klebsiella pneumoniae, a common cause of urinary tract infections for which nitrofurantoin is the recommended treatment. We found that the expression of multiple genes related to membrane transport (including active efflux and passive diffusion of drug molecules) and nitroreductase activity was modified in nitrofurantoin-resistant strains, including oqxR, the transcriptional regulator of the oqxAB efflux pump. Furthermore, complex interconnected metabolic pathways that potentially govern the nitrofurantoin-killing mechanisms (e.g., aminoacyl-tRNA biosynthesis) and nitrofurantoin resistance (riboflavin metabolism) were significantly inhibited following nitrofurantoin treatment. Our study could help inform the improvement of nitrofuran derivatives, the development of new pharmacophores, or drug combinations to support the resurgence of nitrofurantoin in the management of multidrug resistant K. pneumouniae infection.

Dataset Information

Comparative Genomics Analysis of Plasmid pPV989-94 from a Clinical Isolate of Pantoea vagans PV989.

Publications

Comparative Genomics Analysis of Plasmid pPV989-94 from a Clinical Isolate of <i>Pantoea vagans</i> PV989.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets