C. Lim

Candida and invasive candidiasis: back to basics

The ubiquitous Candida spp. is an opportunistic fungal pathogen which, despite treatment with antifungal drugs, can cause fatal bloodstream infections (BSIs) in immunocompromised and immunodeficient persons. Thus far, several major C. albicans virulence factors have been relatively well studied, including morphology switching and secreted degradative enzymes. However, the exact mechanism of Candida pathogenesis and the host response to invasion are still not well elucidated. The relatively recent discovery of the quorum-sensing molecule farnesol and the existence of quorum sensing as a basic regulatory phenomenon of the C. albicans population behavior has revolutionized Candida research. Through population density regulation, the quorum-sensing mechanism also controls the cellular morphology of a C. albicans population in response to environmental factors, thereby, effectively placing morphology switching downstream of quorum sensing. Thus, the quorum-sensing phenomenon has been hailed as the ‘missing piece’ of the pathogenicity puzzle. Here, we review what is known about Candida spp. as the etiological agents of invasive candidiasis and address our current understanding of the quorum-sensing phenomenon in relation to virulence in the host.

Inhibition of hyphae formation and SIR2 expression in Candida albicans treated with fresh Allium sativum (garlic) extract.

Aims:  The aims of the present study were to determine whether Allium sativum (garlic) extract has any effect on the morphology transformation of Candida albicans, and to investigate whether it could alter the gene expression level of SIR2, a morphogenetic control gene and SAP4, a gene encoding secreted aspartyl proteinase.

An alternative Candida spp. cell wall disruption method using a basic sorbitol lysis buffer and glass beads.

This report describes a modified, cost-effective method of cell wall disruption for the yeast Candida spp., which employs the use of glass beads in a simple sorbitol lysis buffer. This method can be used in conjunction with a commercial RNA or genomic DNA isolation method to obtain high-quality RNA or DNA.

Transcriptome profiling of endothelial cells during infections with high and low densities of C. albicans cells

Systemic infections of Candida albicans, the most prevalent fungal pathogen in humans, are on the rise in recent years. However, the exact mode of pathogenesis of this fungus is still not well elucidated. Previous studies using C. albicans mutants locked into the yeast form via gene deletion found that this form was avirulent and did not induce significant differential expression of host genes in vitro. In this study, a high density of C. albicans was used to infect human umbilical vein endothelial cells (HUVEC), resulting in yeast-form infections, whilst a low density of C. albicans resulted in hyphae infections. Transcriptional profiling of HUVEC response to these infections showed that high densities of C. albicans induced a stronger, broader transcriptional response from HUVEC than low densities of C. albicans infection. Many of the genes that were significantly differentially expressed were involved in apoptosis and cell death. In addition, conditioned media from the high-density infections caused a significant reduction in HUVEC viability, suggesting that certain molecules released during C. albicans and HUVEC interactions were capable of causing cell death. This study has shown that C. albicans yeast-forms, at high densities, cannot be dismissed as avirulent, but instead could possibly contribute to C. albicans pathogenesis.

2-dodecanol (decyl methyl carbinol) inhibits hyphal formation and SIR2 expression in C. albicans.

Candida albicans is capable of undergoing yeast‐hypha transition to attain pathogenicity in humans. In this study, we investigated the differential expression of CaSIR2 via quantitative real‐time PCR (qPCR), during yeast‐hypha transition with and without the presence of 2‐dodecanol. SIR2 transcript levels were found to be significantly enhanced after hyphal induction as compared to the yeast form. This study found that 2‐dodecanol is able to inhibit hyphal development and block SIR2 up‐regulation, even in hyphal‐inducing growth conditions. We suggest that SIR2 may be involved in Candida albicans quorum‐sensing and serum‐induced yeast‐hyphae transition via the Ras1‐cAMP‐Efg1 signalling cascade. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Is the Quality of Life in Breast Cancer Survivors the Same as Healthy Women? A Case Control Study Among Women in Klang Valley, Malaysia

Background: One of the positive outcomes of improvements in cancer care is the increasing number of people who survive the disease. Worldwide, the number of cancer survivors will continue to increase, with a threefold increase predicted from 25 million in 2008 to 75 million in 2030. Breast cancer survivors have the highest survival rates compared other types of cancer. Following a diagnosis of breast cancer, issues that women often worry about include the possibility of cancer recurrence, challenges with reacclimatizing to daily life posttreatment completion and numerous other emotional and physical challenges. It is unknown whether over time the coping skills of these survivors enable them to have a similar quality of life (QOL) as other normal women. This study aimed to assess and compare the quality of life (QOL) among breast cancer survivors and nonbreast cancer survivors in the Klang Valley, Malaysia. Methods: This case-control study used the European Organization for Research and Treatment of Cancer...

Factors Associated With an Abnormal Mammogram Finding in Women Undergoing Screening in Kuala Lumpur, Malaysia

Background: Breast cancer is the most common cancer among Malaysian women, with a rising incidence from 16.5% in 2006%–17.7% in 2011. One of the key strategies in breast cancer control is early screening; of which mammography is a highly accurate tool, having been shown to reduce the number of mortality rates due to breast cancer up to 30%. However, mammography is often not as widely available in Malaysia; and in many local settings, healthcare providers have to limit screenings to only particular groups such as those with abnormal clinical breast examinations due to limited resources. Knowledge of other predictive factors may assist in further decision-making to prioritize patients for screening mammography in a low-resource setting. Aim: This study aimed to determine such predictive factors for abnormal mammogram findings among women who underwent mammography examination at a center in Kuala Lumpur, Malaysia. Methods: This was a cross-sectional study of women (n = 5491) who underwent a three-dimensional...