Contrary to what you might think, microbes – not guns – were the biggest killers of soldiers during the American Civil War (1861-1865). For every three men killed in the field, five died from disease, often the result of an infected wound.

So, naturally, when Union forces instigated a blockade stripping the south of crucial medication (e.g. quinine, morphine, and chloroform), things were looking bleak for the Confederate side.

In response to the blockade, a botanist called Francis Porcher was asked to find and catalog flora native to the southeastern states that could be used as alternative medicines. Now, for the first time, researchers are looking into the antiseptic properties of three of the medicines he listed in the Civil War plant guide (Resources of the Southern Fields and Forests, published 1863): white oak, tulip poplar, and the devil’s walking stick. The results are published in Scientific Reports.

Traditional plant medicines are often dismissed if they don’t actively kill disease-causing bacteria, lead author Cassandra Quave, an ethnobiologist at Emory University, said in a statement. Quave researches plant used in traditional healing practices to find candidates for new drugs.

"There are many more ways to help cure infections, and we need to focus on them in the era of drug-resistant bacteria," she added.

The US Civil War is the single bloodiest conflict in the country's history, with more military losses (620,000) than WW1 (116,516), WW2 (405,399), Vietnam (58,209), and Korea (36,516) combined. Of those that made it out, one in 13 came home with one or more missing limbs. Source: The American Battlefield Trust. Picture: Private John J. Williams of the 34th Indiana Regiment Volunteer Infantry, the last soldier to die in the Civil War. Public Domain

Quave and colleagues tested the folk remedies against a trio of multi-drug-resistant bacteria: Acinetobacter baumannii, Staphylococcus aureus, and Klebsiella pneumoniae. Samples of the plants were collected as per Porcher’s recommendations and laboratory tests revealed the effectiveness of different extracts on the various strains of bacteria.

First up, A. baumannii (or “Iraqibacter”, a reference to its association with troops wounded during the Iraq War), which shows resistance to the vast majority of frontline drugs – but, excitingly, not to white oak, whose application appeared to inhibit the growth of the bacteria.

That is promising stuff – as Quave points out, A. baumannii is "emerging as a major threat for soldiers recovering from battle wounds and for hospitals in general."

Next, S. aureus, widely considered to be the most dangerous common staph infection. The researchers found that they could inhibit the growth of the bacteria by applying extracts of tulip poplar to the sample. What’s more, the application of all three plants appeared to block its ability to form biofilms, a defense that helps protect the bacteria against antibiotics. Meanwhile, the application of the devil’s walking stick prevented the bacteria from quorum sensing. That is a signaling system that boosts toxin production. Dismantling it, therefore, “disarms” the bacteria.

Finally, K. pneumoniae – a particularly nasty bacteria that can cause pneumonia, septic shock, and ultimately, death. Again, the researchers were able to inhibit its growth with the application of white oak.

One in four drugs is derived from natural products found in traditional medicine, while an estimated 4 billion people worldwide use traditional medicine (and natural products) as their primary source of healthcare. With the growing threat of antibiotic resistance (listed as a global threat, as per the World Health Organization), natural product extracts could be a way forward.

"Given the great genetic diversity and capacity for evolution present in bacteria, a rise in antibiotic resistance is an inevitable response to antibiotic use," the study authors write.

"One benefit of natural product extracts as antibiotic agents over single-compound drugs is that due to the presence of dozens to thousands of compounds, they can exhibit multiple mechanisms of activity, potentially making it more difficult for resistance to develop."