Hot Off the Press – Cavities and Cardio
Streptococcus sanguinis is a member of the human indigenous oral microbiota. It is a normal inhabitant of the healthy human mouth and appears to confer some resistance to cavities by slowing the growth of S. mutans, a cavity causing bacteria. However, if S sanguinis enters the bloodstream, for example through dental surgical procedures or even daily flossing and brushing, it can colonize heart valves and cause infective endocarditis (IE), a serious endovascular infection that carries a high risk of morbidity and mortality and is the fourth leading cause of life-threatening infectious disease syndromes.
Streptococci such S. sanguinis are becoming increasingly resistant to antibiotics and this has led to reluctance to prescribe antibiotics prophylactically. This highlights the need for the advancement of preventative measures against IE, for which no vaccine exists. If we can understand the biology of S sanguinis perhaps we can target the bacteria more effectively and prevent cases of IE.
Spx proteins are a group of global regulators that control transcription of genes in bacteria in response to oxidative stress, developmental programs and energy consuming related growth. Through a series of elegant experiments using mutant genes this paper shows that SpxA1 is involved in hydrogen peroxide (H2O2) production, stress tolerance and IE virulence.
A ΔspxA1 mutant of S. sanguinis
- produces less H2O2 and is less effective at curbing the growth of the cavity causing S. mutans.
- shows a decreased tolerance to high temperature, acidic and oxidative stresses
- is less effective at colonizing heart valves and causing IE in animal models
This suggests a link between the stress survival mechanisms in S. sanguinis and its virulence in causing IE. This is perhaps not surprising as the pathogenesis of IE is a multi-step process and various stresses are involved during its development such as the oxidative stress in the blood.
This paper shows for the first time the involvement of Spx proteins in virulence and specifically in IE virulence. Further investigations on Spx proteins will provide vital information required to better understand bacterial regulatory mechanisms involved in not only IE virulence but also stress tolerance. Further investigation will help us to understand the virulence of this factor and help us target ways to reduce S. sanguinis causing IE. The long term goal is to develop strategies to control oral streptococcal related infectious diseases.
Ping Xu is an associate professor in the Philips Institute of Oral and Craniofacial Molecular Biology. This work was supported by grants R01DE018138 from the National Institutes of Health (PX) and in part, by Virginia Commonwealth University Presidential Research Incentive Program (PRIP) 144602-3 (PX). To read the full paper go to http://www.ncbi.nlm.nih.gov/pubmed/22768210
Categories Research