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Open Access Highly Accessed Research article

Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans

Mohan Pammi1*, Rong Liang1, John Hicks2, Toni-Ann Mistretta2 and James Versalovic2

Author Affiliations

1 Section of Neonatology, Department of Pediatrics, Texas Children’s Hospital & Baylor College of Medicine, 6621, Fannin, MC: WT 6-104, Houston, TX 77030, USA

2 Department of Pathology, Texas Children’s Hospital & Baylor College of Medicine, Houston, TX 77030, USA

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BMC Microbiology 2013, 13:257  doi:10.1186/1471-2180-13-257

Published: 14 November 2013

Abstract

Background

Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm formation and pose a significant risk for polymicrobial infections. We hypothesized that enhancement of biofilms in a mixed species environment increases patient mortality and morbidity.

Results

Mixed species biofilms of S. epidermidis and C. albicans were evaluated in vitro and in a subcutaneous catheter infection model in vivo. Mixed species biofilms were enhanced compared to single species biofilms of either S. epidermidis or C. albicans. A mixed species environment increased catheter infection and increased dissemination of S. epidermidis in mice. Microarrays were used to explore differential gene expression of S. epidermidis in the mixed species biofilms. In mixed species biofilms, compared to single species S. epidermidis biofilms, 2.7% of S. epidermidis genes were upregulated and 6% were down regulated. Staphylococcal autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively. The role of biofilm extracellular DNA was investigated by quantitation and by evaluating the effects of DNAse in a concentration and time dependent manner. S. epidermidis specific eDNA was increased in mixed species biofilms and further confirmed by degradation with DNAse.

Conclusions

Mixed-species biofilms are enhanced and associated with increased S. epidermidis-specific eDNA in vitro and greater systemic dissemination of S. epidermidis in vivo. Down regulation of the lrg operon, a repressor of autolysis, associated with increased eDNA suggests a possible role for bacterial autolysis in mixed species biofilms. Enhancement and systemic dissemination of S. epidermidis may explain adverse outcomes after clinical polymicrobial infections of S. epidermidis and C. albicans.

Keywords:
Staphylococcus; Candida; Biofilms; Microarray; Extracellular DNA; Autolysis; Polymicrobial; Mixed species