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29 July 2014

978 1 90445 513 4
Caister Academic Press
GBP 159.00

Candida: Comparative and Functional Genomics

Christophe d’Enfert and Bernhard Hube (eds)

In the introduction to this book, the authors readily admit the pitfalls and perils of conducting research on the opportunistic pathogen family, Candida. First, the organism exists as a diploid species which lacks an exploitable sexual cycle with a haploid phase, thus using post-genomic interventions to construct knockout mutants is a long and labour intensive exercise. Also, Candida has a unique genetic quirk; the CUG codon is translated into a serine instead of a leucine residue. This genetic anomaly becomes frustrating when using reporter systems or attempting heterologous expression of Candida proteins in other expression systems. Even though the genomes of most Candida species have been sequenced, these technicalities have been instrumental in slowing down advancements in Candida research, especially when compared with its near relative, Saccharomyces cerevisiae. That said, significant advancements in S. cerevisiae research has greatly informed Candida biology as core mechanisms, DNA sequences and protein functions are widely conserved between the two species. These genomic insights have assisted clinical researchers unravel the role that Candida plays as an opportunistic pathogen in human disease. Cited as one of the most insidious nosocomial infections, the organism infects immuno-compromised patients, causes systemic infections in cancer and organ transplant patients and leads to the bloodstream infection, candidemia. Candida: Comparative and Functional Genomics attempts to unravel the latest molecular mechanisms on Candida pathogenesis and asks why it is such a prolific infectious offender.

Split into 17 chapters, the book commences with genome structure. Candida albicans is quite an astonishing organism with several unique features. With eight pairs of chromosomes, amounting to a haploid complement of 16 Mb DNA, the genome is highly plastic and fluid thanks to distinct repeated sequences at the DNA level [ribosomal DNA and major repeat sequences (MRS)] and high frequencies of regions of high heterozygosity. Combined with other genomic instabilities (retro-transposon disruption of DNA, allelic sequence divergence and gene duplication), this allows for dynamic rearrangements leading to several karyotypes responsible for a plethora of adaptive infection mechanisms.

Further in, another Candida quirk is revealed. The yeast-to-hypha transition incorporates dramatic changes in cell morphology and concomitant alterations in the expression profiles of some metabolic proteins, namely cell wall proteins (CWPs). Traditionally, it had been assumed that the adherent filamentous forms were implicated in the pathogenic generation of biofilms and virulence was involved in infection, however, in the yeast form, there may be a size advantage to infection of the host through the circulatory system or tissue. In the laboratory, in vitro studies have elucidated dramatic changes in protein expression in line with the yeast-to-hypha transition; sequential fractionation and two-dimensional electrophoresis have revealed alterations in several CWPs, reflective of a gross cell wall remodelling during the morphological transition. Incorporating such a micro/macro approach to its infectivity cycle, Candida has well and truly earned its colours as an opportunistic pathogen.

Later, there is an excellent chapter on genomic analysis of pathogenesis. Although not clearly delineating any one pathogenic mechanism, the current literature is well reviewed and presented with unambiguous arguments put forward. What is clear is that Candida can discern different immune cell types and respond accordingly, either expansively with global alterations in the expression of hundreds of genes or exquisitely, with a small cohort of genes switched on to match a particular response, e.g. iron uptake. The complexity of these responses does not lend itself to easy study and analysis.

The book is well written, clear and extremely well referenced. In some chapters there is a dearth of diagrams and figures but this can be forgiven owing to the clarity of the writing. The index abounds with individual gene names and families so readers can find their favourites, while for those interested in technical aspects, references to post-genomic and proteomic tools abound. This book works well because it contains one central premise: the understanding of molecular mechanisms behind the pathogenic Candida. Retailing at £159, this is an inexpensive price for good science.

John P. Phelan (Waterford Institute of Technology, Ireland)



 
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