Typing Staphylococcus aureus Using the spa Gene and Novel Distance Measures

We developed an approach for identifying groups or families of Staphylococcus aureus bacteria based on genotype data. With the emergence of drug-resistant strains, S. aureus represents a significant human health threat. Identifying the family types efficiently and quickly is crucial in community settings. Here, we develop a hybrid sequence algorithm approach to type this bacterium using only its spa gene. Two of the sequence algorithms we used are well established, whereas the third, the best common gap-weighted sequence (BCGS), is novel. We combined the sequence algorithms with a weighted match/mismatch algorithm for the spa sequence ends. Normalized similarity scores and distances between the sequences were derived and used within unsupervised clustering methods. The resulting spa groupings correlated strongly with the groups defined by the well-established multilocus sequence typing (MLST) method, spa typing is preferable to MLST typing, which types seven genes instead of just one. Furthermore, our spa clustering methods can be fine-tuned to be more discriminating than MLST, identifying new strains that the MLST method may not. Finally, we performed a multidimensional scaling of our distance matrices to visualize the relationship between isolates. The proposed methodology provides a promising new approach to molecular epidemiology.

1 Introduction

Staphylococcus aureus is a common bacterium that often resides quite harmlessly on the skin or in the nose of a healthy person. However, a break in the skin or a weakened immune system can trigger the bacteria to cause minor skin infections or life-threatening diseases such as pneumonia, septicemia, and meningitis. Such infections can be passed on through skin contact or contaminated objects. It is no wonder then that S. aureus is the leading cause of hospital-acquired infections in the United States. Controlling and understanding S. aureus in both hospital and community settings is a significant public health concern that is underscored by the continuous evolution and development of methicillin-resistant S. aureus (MRSA). Recent advances in biotechnology allow molecular epidemiology to play an increasing role in the control of S. aureus [2]. Genotyping these bacteria is critical for the study of strain origin, epidemiology of strain outbreaks, and clonal relatedness and is an invaluable tool for the investigation of hospital outbreaks.