whole-genome-sequencing-candida-glabrata-for-detection-markers

Whole Genome Sequencing of <em>Candida glabrata</em> for Detection of Markers of Antifungal Drug Resistance

Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations ...

Westmead hospital

Detection of pyrazinamide resistance in Mycobacterium tuberculosis isolates presents significant challenges in settings with no dominant clonal lineages, such as Australia. We assessed the utility of WGS versus standard PCR amplification assays for the characterization of pyrazinamide resistance in MDR-TB isolates identified in New South Wales, Australia, over an 8 year period.

Genome sequencing reveals novel deletions associated with secondary resistance to pyrazinamide in MDR Mycobacterium tuberculosis.

The control of food-borne outbreaks caused by Listeria monocytogenes in humans relies on the timely identification of food or environmental sources and the differentiation of outbreak-related isolates from unrelated ones. This study illustrates the utility of whole-genome sequencing for examining the link between clinical and environmental isolates of L. monocytogenes associated with an outbreak of hospital-acquired listeriosis in Sydney, Australia. Comparative genomic analysis confirmed an epidemiological link between the three clinical and two environmental isolates. Single nucleotide polymorphism (SNP) analysis showed that only two SNPs separated the three human outbreak isolates, which differed by 19 to 20 SNPs from the environmental isolates and 71 to >10,000 SNPs from sporadic L. monocytogenes isolates. The chromosomes of all human outbreak isolates and the two suspected environmental isolates were syntenic. In contrast to the genomes of background sporadic isolates, all epidemiologically linked isolates contained two novel prophages and a previously unreported clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) locus subtype sequence. The mobile genetic element (MGE) profile of these isolates was distinct from that of the other serotype 1/2b reference strains and sporadic isolates. The identification of SNPs and clonally distinctive MGEs strengthened evidence to distinguish outbreak-related isolates of L. monocytogenes from cocirculating endemic strains.

It Is Not All about Single Nucleotide Polymorphisms: Comparison of Mobile Genetic Elements and Deletions in Listeria monocytogenes Genomes Links Cases of Hospital-Acquired Listeriosis to the Environmental Source.

Improved tuberculosis control and the need to contain the spread of drug-resistant strains provide a strong rationale for exploring tuberculosis transmission dynamics at the population level. Whole-genome sequencing provides optimal strain resolution, facilitating detailed mapping of potential transmission pathways.

Identifying Likely Transmission Pathways within a 10-Year Community Outbreak of Tuberculosis by High-Depth Whole Genome Sequencing.

dfrA thyA Double Deletion in para-Aminosalicylic Acid-Resistant Mycobacterium tuberculosis Beijing Strains.

Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tuberculosis, are nontoxic to human cell lines, and are active against multidrug-resistant M. tuberculosis strains, indicating a distinct mode of action. These compounds warrant further appraisal as novel agents to control TB in humans.

Nontoxic Metal-Cyclam Complexes, a New Class of Compounds with Potency against Drug-Resistant Mycobacterium tuberculosis.

The city of Sydney, Australia, experienced a persistent outbreak of Legionella pneumophila serogroup 1 (Lp1) pneumonia in 2016. To elucidate the source and guide public health actions the genomes of clinical and environmental Lp1 isolates recovered over 7 weeks were examined. A total of 48 isolates from human cases and cooling towers were sequenced and compared using SNP-based, core-genome MLST and pangenome approaches. All three methods confirmed phylogenetic relatedness between isolates associated with outbreaks in the Central Business District (CBD) in March and May and Suburb 1. These isolates were designated "Main cluster" and consisted of isolates from two patients from the CBD March outbreak, one patient and one tower isolate from Suburb 1 and isolates from two cooling towers and three patients from the CDB May outbreak. All main cluster isolates were sequence type (ST)211 which previously has only been reported in Canada. Significantly, pangenome analysis identified mobile genetic elements containing a unique T4ASS that was specific to the main cluster and co-circulating clinical strains, suggesting a potential mechanism for increased fitness and persistence of the outbreak clone. Genome sequencing enabled linking the geographically dispersed environmental sources of infection among the spatially and temporally coinciding cases of legionellosis in a highly populated urban setting. The discovery of a unique T4ASS emphasises the role of genome recombination in the emergence of successful Lp1 clones.Importance A new emerging clone has been responsible for a prolonged legionellosis outbreak in Sydney, Australia. The use of whole genome sequencing linked two outbreaks thought to be unrelated and confirmed outliers. These findings led to the re-sampling and subsequent identification of the source, guiding public health actions and bringing the outbreak to a close. Significantly, the outbreak clone was identified as sequence type (ST) 211. Our study reports this ST in the southern hemisphere and presents a description of ST211 genomes from both clinical and environmental isolates. A unique mobile genetic element containing a Type IV secretion system was identified in Lp1 ST211 isolates linked to the main cluster and Lp1 ST42 isolates that were co-circulating at the time of the outbreak.

Article	Year
Genome sequencing reveals novel deletions associated with secondary resistance to pyrazinamide in MDR Mycobacterium tuberculosis. The Journal of antimicrobial chemotherapy\| PubMed ID: 25977398	2015
It Is Not All about Single Nucleotide Polymorphisms: Comparison of Mobile Genetic Elements and Deletions in Listeria monocytogenes Genomes Links Cases of Hospital-Acquired Listeriosis to the... Journal of clinical microbiology\| PubMed ID: 26311854	2015
Identifying Likely Transmission Pathways within a 10-Year Community Outbreak of Tuberculosis by High-Depth Whole Genome Sequencing. PloS one\| PubMed ID: 26938641	2016
dfrA thyA Double Deletion in para-Aminosalicylic Acid-Resistant Mycobacterium tuberculosis Beijing Strains. Antimicrobial agents and chemotherapy\| PubMed ID: 27021327	2016
Nontoxic Metal-Cyclam Complexes, a New Class of Compounds with Potency against Drug-Resistant Mycobacterium tuberculosis. Journal of medicinal chemistry\| PubMed ID: 27214150	2016
Genome sequencing links persistent outbreak of legionellosis in Sydney to an emerging clone of Legionella pneumophila ST211. Applied and environmental microbiology\| PubMed ID: 29247056	2017

Elena Martinez

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