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Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli.

ABSTRACT: Neonatal meningitis is a rare but devastating condition. Multi-drug resistant (MDR) bacteria represent a substantial global health risk. This study reports on an aggressive case of lethal neonatal meningitis due to a MDR Escherichia coli (serotype O75:H5:K1). Serotyping, MDR pattern and phylogenetic typing revealed that this strain is an emergent and highly virulent neonatal meningitis E. coli isolate. The isolate was resistant to both ampicillin and gentamicin; antibiotics currently used for empiric neonatal sepsis treatment. The strain was also positive for multiple virulence genes including K1 capsule, fimbrial adhesion fimH, siderophore receptors iroN, fyuA and iutA, secreted autotransporter toxin sat, membrane associated proteases ompA and ompT, type II polysaccharide synthesis genes (kpsMTII) and pathogenicity-associated island (PAI)-associated malX gene. The presence of highly-virulent MDR organisms isolated in neonates underscores the need to implement rapid drug resistance diagnostic methods and should prompt consideration of alternate empiric therapy in neonates with Gram negative meningitis.

SUBMITTER: Iqbal J

PROVIDER: S-EPMC4818964 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli.

Iqbal Junaid J Dufendach Kevin R KR Wellons John C JC Kuba Maria G MG Nickols Hilary H HH Gómez-Duarte Oscar G OG Wynn James L JL

Infectious diseases (London, England) 20160219 6

Neonatal meningitis is a rare but devastating condition. Multi-drug resistant (MDR) bacteria represent a substantial global health risk. This study reports on an aggressive case of lethal neonatal meningitis due to a MDR Escherichia coli (serotype O75:H5:K1). Serotyping, MDR pattern and phylogenetic typing revealed that this strain is an emergent and highly virulent neonatal meningitis E. coli isolate. The isolate was resistant to both ampicillin and gentamicin; antibiotics currently used for em ...[more]

PMID: 27030919

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Project description:To characterize the differentially expressed genes between pathogenic avian E. coli and human E. coli ATCC 25922, Abstract Escherichia coli (E. coli) is a harmless common bacterium of poultry intestine, but with a wide range of genomic flexibility, is also causative agent of many poultry diseases collectively called colibacillosis that is blamed for high economic loss in poultry sector worldwide. Numerous studies have been conducted to check the prevalence of pathogenic E. coli in poultry and poultry products, however limited data are available regarding their resistance and virulence associated genes expression profile. This study examined the pathogenomic content of poultry E. coli by antibiotic susceptibility, biofilm formation and adhesion, invasion and intracellular survivability assays in Caco-2 and Raw 264.7 cell lines along with the determination of median lethal dose in two-day old chickens. A clinical pathogenic multidrug resistant (MDR) isolate, E. coli 381, isolated from broilers was found to be highly virulent in cell culture and in chicken model. Transcriptome analysis has been skewed towards bacterial pathogens because of the prioritization of poultry diseases. Comparative gene expression profile of MDR E. coli 381 and the reference human strain E. coli ATCC 25922 was done using Illumina HiSeq2500 transcriptome and results were verified by RT-qPCR analyses. A number of resistant encoding genes including multidrug transporters, multidrug resistance proteins, porins and autotransporters were identified. We also noticed overexpression of very important virulent genes (fimA, fimC, fimH and fimI) encoding the type-1 fimbrial proteins, curli fimbriae genes , invasin genes, toxin-encoding genes and biofilm forming regulatory genes . In addition, many types of stress and metal homeostasis controlling genes were among up-regulated genes in E. coli 381 as compared to reference strain. GO and KEGG pathway analysis results revealed that genes controlling secondary metabolism, drug transport, adhesion and invasion proteins, and mobile genetic elements were over-expressed in E. coli 381. Several genes involved in cellular and metabolic processes such as carbohydrate metabolism were responsible for stress tolerance. Seminal description of the transcriptomic results and other unique features of E. coli 381 confirmed that it is highly virulent and MDR strain of poultry origin. This comparative study provides new avenues for further work on molecular mechanisms to prevent resistance development in bacteria and to ensure public health.

Project description:Resistance to last-line polymyxins mediated by the plasmid-borne mobile colistin resistance gene (mcr-1) represents a new threat to global human health. Here we present the complete genome sequence of an mcr-1-positive multidrug-resistant Escherichia coli strain (MS8345). We show that MS8345 belongs to serotype O2:K1:H4, has a large 241,164-bp IncHI2 plasmid that carries 15 other antibiotic resistance genes (including the extended-spectrum β-lactamase blaCTX-M-1) and 3 putative multidrug efflux systems, and contains 14 chromosomally encoded antibiotic resistance genes. MS8345 also carries a large ColV-like virulence plasmid that has been associated with E. coli bacteremia. Whole-genome phylogeny revealed that MS8345 clusters within a discrete clade in the sequence type 95 (ST95) lineage, and MS8345 is very closely related to the highly virulent O45:K1:H4 clone associated with neonatal meningitis. Overall, the acquisition of a plasmid carrying resistance to colistin and multiple other antibiotics in this virulent E. coli lineage is concerning and might herald an era where the empirical treatment of ST95 infections becomes increasingly more difficult.IMPORTANCEEscherichia coli ST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of an E. coli ST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-borne mcr-1 gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage.

Dataset Information

Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli.

Publications

Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli.

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