Oral Bacteria Require Manganese to Cause Endocarditis

In order to grow normally, bacteria such as Streptococcus sanguinis need manganese, according to joint studies published in The Journal of Biological Chemistry. S. sanguinis, which lives in the mouth, is a precursor to endocarditis.

When the researchers at the Virginia Commonwealth University Philips Institute for Oral Health eliminated the enzyme that requires manganese from the bacterium, it did not survive or cause endocarditis in animal models. This research confirms the longstanding knowledge that manganese was required for some function in bacteria responsible for serious infections.

“The best antibiotics attack parts of a bacterium that are critical for bacterial survival, but are not found in human cells,” Todd Kitten, PhD, associate professor at the Philips Institute School of Dentistry, said in a statement. “The manganese-requiring enzyme meets both requirements because these bacteria need it to survive and humans use a very different, iron-containing enzyme to make DNA building blocks. It is the manganese requirement that makes the bacterial proteins good targets.”

Other investigators at the Massachusetts Institute of Technology examined the purified enzymes to determine their functions. The scientists aim to target other likely manganese-requiring enzymes in bacteria that cause diseases such as MRSA, Streptococcus pyogenes, and the anthrax bacteria. They are also exploring what other effects manganese has on the bacteria.

These studies fuel the search for more effective antibiotics. The research team is preparing to collaborate with Glen Kellogg, PhD, associate professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy, to create designer drugs to disrupt the manganese uptake system in these bacteria. Kitten noted that humans have very little manganese in their bodies, so the bacteria have developed specialized systems to acquire it.