A hybridization target enrichment approach for pathogen genomics.

Emerging infectious diseases require continuous pathogen monitoring. Rapid clinical diagnosis by nucleic acid amplification is limited to a small number of targets and may miss target detection due to new mutations in clinical isolates. Whole-genome sequencing (WGS) identifies genome-wide variations that may be used to determine a pathogen's drug resistance patterns and phylogenetically characterize isolates to track disease origin and transmission.

Validation and Implementation of Clinical Laboratory Improvements Act-Compliant Whole-Genome Sequencing in the Public Health Microbiology Laboratory.

Public health microbiology laboratories (PHLs) are on the cusp of unprecedented improvements in pathogen identification, antibiotic resistance detection, and outbreak investigation by using whole-genome sequencing (WGS). However, considerable challenges remain due to the lack of common standards. Here, we describe the validation of WGS on the Illumina platform for routine use in PHLs according to Clinical Laboratory Improvements Act (CLIA) guidelines for laboratory-developed tests (LDTs).

Dual Targeting of Mesenchymal and Amoeboid Motility Hinders Metastatic Behavior.

Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC).

Recent Outbreaks of Shigellosis in California Caused by Two Distinct Populations of with either Increased Virulence or Fluoroquinolone Resistance.

has caused unusually large outbreaks of shigellosis in California in 2014 and 2015. Preliminary data indicated the involvement of two distinct bacterial populations, one from San Diego and San Joaquin (SDi/SJo) and one from the San Francisco (SFr) Bay area. Whole-genome analysis and antibiotic susceptibility testing of 68 outbreak and archival isolates of were performed to investigate the microbiological factors related to these outbreaks.

Laboratory Investigation of Salmonella enterica serovar Poona Outbreak in California: Comparison of Pulsed-Field Gel Electrophoresis (PFGE) and Whole Genome Sequencing (WGS) Results.

Introduction: Recently, serovar Poona caused a multistate outbreak, with 245 out of 907 cases occurring in California. We report a comparison of pulsed-field gel electrophoresis (PFGE) results with whole genome sequencing (WGS) for genotyping of Poona isolates.

Methods: CA Poona isolates, collected from July to August 2015, were genotyped by PFGE using XbaI restriction enzyme.

Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule-targeting drug eribulin on different stages of metastasis in triple-negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer.

Draft Genome Sequence of Turicella otitidis TD1, Isolated from a Patient with Bacteremia.

We report the draft genome sequence of Turicella otitidis strain TD1, isolated from a central line catheter sample from a patient with a history of bowel obstruction. It contained several genetic determinants of multidrug-resistant phenotypes such as a cfrA 50S methyltransferase, two major facilitator superfamily-type drug resistance transporters, and a putative beta-lactamase.

Draft Genome Sequence of Kerstersia gyiorum CG1, Isolated from a Leg Ulcer.

We report the first draft genome sequence of Kerstersia gyiorum from a leg ulcer of a patient with diabetes and osteomyelitis. The 3.94-Mb genome assembly included 3,428 annotated coding sequences with an N50 of 223,310 bp and a plasmid encoding a type IV secretion system gene and two antitoxin genes.

Long-term dissemination of CTX-M-5-producing hypermutable Salmonella enterica serovar typhimurium sequence type 328 strains in Russia, Belarus, and Kazakhstan.

In this paper, we present evidence of long-term circulation of cefotaxime-resistant clonally related Salmonella enterica serovar Typhimurium strains over a broad geographic area. The genetic relatedness of 88 isolates collected from multiple outbreaks and sporadic cases of nosocomial salmonellosis in various parts of Russia, Belarus, and Kazakhstan from 1996 to 2009 was established by multilocus tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST). The isolates belong to sequence type 328 (ST328) and produce CTX-M-5 β-lactamase, whose gene is carried by highly related non-self-conjugative but mobilizable plasmids.

NEDD9 regulates actin dynamics through cortactin deacetylation in an AURKA/HDAC6-dependent manner.

Unlabelled: The prometastatic protein NEDD9 (neural precursor cell expressed, developmentally downregulated 9) is highly expressed in many cancers and is required for mesenchymal individual cell migration and progression to the invasive stage. Nevertheless, the molecular mechanisms of NEDD9-driven migration and the downstream targets effecting metastasis are not well defined. In the current study, knockdown of NEDD9 in highly metastatic tumor cells drastically reduces their migratory capacity due to disruption of actin dynamics at the leading edge.

Bacterial resistance studies using in vitro dynamic models: the predictive power of the mutant prevention and minimum inhibitory antibiotic concentrations.

In light of the concept of the mutant selection window, i.e., the range between the MIC and the mutant prevention concentration (MPC), MPC-related pharmacokinetic indices should be more predictive of bacterial resistance than the respective MIC-related indices.

Convergent in vivo and in vitro selection of ceftazidime resistance mutations at position 167 of CTX-M-3 beta-lactamase in hypermutable Escherichia coli strains.

We report on a novel CTX-M extended-spectrum beta-lactamase (ESBL), designated CTX-M-42, with enhanced activity toward ceftazidime. CTX-M-42 was identified in a hypermutable Escherichia coli nosocomial isolate (isolate Irk2320) and is a Pro167Thr amino acid substitution variant of CTX-M-3. By molecular typing of ESBL-producing E.