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

A human isolate of Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis 43525) was sequenced and compared genomically to other mycobacterial pathogens. M. paratuberculosis 43525 was recently isolated from a patient with ulcerative colitis and belongs to the M. avium complex, a group known to infect both humans and animals. While M. paratuberculosis is a known pathogen of livestock, there are only 20 human isolates from the last 20 years, therefore we took the opportunity to perform a whole genome comparison between human and animal mycobacterial pathogens. We also compared virulence determinants such as the mycobactin cluster, PE/PPE genes and mammalian cell entry (mce) operons between MAC subspecies that infect animals and those that infect humans. M. tuberculosis was also included in these analyses given its predominant role as a human pathogen.

Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity.

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
Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity. BMC genomics\| PubMed ID: 26370227	2015
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

Verlaine J. Timms

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