Candida spp. are the most common causes of fungal infections worldwide. Among the Candida species, Candida albicans remains the predominant species that causes invasive candidiasis in most countries. In this study, we used two peptides, KABT-AMP and uperin 3.6 as templates to develop novel antifungal peptides. Their anticandidal activity was assessed using a combination of MIC, time-killing assay and biofilm reduction assay. Hybrid peptides, KU2 and KU3 containing a mixed backbone of KABT-AMP and Uperin 3.6 demonstrated the most potent anticandidal activity with MIC values ranging from 8–16 mg/L. The number of Trp residues and the amphipathic structure of peptides probably enhanced the anticandidal activity of peptides. Increasing the cationicity of the uperin 3.6 analogues resulted in reduced MIC from the range of 64–128 mg/L to 16–64 mg/L and this was also correlated with the antibiofilm activity and killing kinetics of the peptides. Peptides showed synergistic effects when used in combination with conventional antifungals. Peptides demonstrated low haemolytic activity but significant toxicity on two normal human epithelial cell lines. This study provides us with a better understanding on the structure-activity relationship and the balance between cationicity and hydrophobicity of the peptides although the therapeutic application of the peptides is limited.

Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.

Abstractobjective To describe a prospective laboratory-based surveillance of Candida species that were collected from different anatomical sites of patients admitted to the University of Malaya Medical Centre, Malaysia, from the year 2000 to 2013.methods Conventional (culture, microscopic examination and carbohydrate assimilation test) and molecular (PCR amplification and DNA sequencing) techniques were used to identify Candida species.results A total of 16 Candida species isolated from 34 392 clinical samples were from the oral cavity (oral swabs and throat swabs), blood, respiratory tract (sputum, tracheal secretions, nasopharyngeal aspirates, bronchoalveolar lavage), high vaginal swab, pus and urine. C. albicans (66.70%, 22 941/34 392), C. glabrata (11.71%, 4029/34 392), C. parapsilopsis (10.74%, 3692/ 34 392), C. tropicalis (9.19%, 3162/34 392) and C. krusei (1.15%, 396/34 392) were the five predominant Candida species. C. albicans was the predominant species isolated from the oral cavity, respiratory tract and high vaginal swab; while the Candida species isolated from blood, urine and pus were predominant non-albicans Candida. Uncommon Candida species, such as C. lusitaniae, C. haemulonii, C. humicola, Pichia ohmeri and C. ciferrii, were also isolated in this study.conclusion Our study expands the current knowledge of the epidemiology of non-invasive and invasive candidiasis in Malaysia. The variability of the Candida species distribution from different anatomical sites highlights the significance of local epidemiology in disease management and selection of antifungal agents.