“What you see is that the most outstanding feature of life's history is a constant domination by bacteria.”
- Stephen Jay Gould, American paleontologist and evolutionary biologist
“From relying on a hive mind, to hedging their bets like seasoned investors, or rapidly adapting by genetic mutation, bacteria seem to have figured out the best way to cope with change is to play every possible trick in the book.”
- Stefany Moreno-Gamez, Ph.D., winner, Science & SciLifeLab Prize for Young Scientists, 2022
Microbes belonging to the domain of life called Bacteria are the ancient ancestors of all living things. While a vast majority of Bacteria don’t cause us any harm, a tiny minority are major trouble-makers. My aim in this Germ Gems post is to update readers on the status of bacterial pathogens including group A strep, a bacterium that is currently bugging an increasing number of people worldwide. In addition, I highlight several recent findings regarding our bacterial friends.
What are bacteria doing to us? In December 2022, Lancet published the article “Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019”—a comprehensive accounting of the global burden of bacterial infections. The 33 bacterial species analyzed in this study were associated with 13.6% of deaths globally in 2019 and five led the list of sepsis-related global killers: Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
When considered together, the 7.7 million bacteria-related deaths in 2019 ranked as the second leading cause of death globally, right behind heart attacks (myocardial infarctions). From a public health perspective, the authors of this study suggested these bacterial pathogens should be regarded an urgent priority for intervention within the global health community. (It should be noted that the bacterium that causes TB, Mycobacterium tuberculosis, wasn’t included in this study. TB is the leading infectious cause of death in the world, killing an estimated 1.6 million people each year.)
Of critical importance are bloodstream infections caused by bacteria that are resistant to “last-resort” antibiotics, a mounting global challenge. In the U.S., cases of bacterial infection of heart valves (endocarditis) are skyrocketing. The top global bacterial killer, S. aureus, is not only linked to more than 1 million deaths annually, but this Gram-positive bacterium is also the leading cause of endocarditis in patients who are dependent on opioids or cocaine. (Sadly, in the U.S., the number of cases of S. aureus endocarditis has increased markedly over the past decade along with the epidemic of drug dependency.)
Recent emergence of invasive group A Streptococcus infections. The Gram-positive bacterium group A streptococcus (GAS) causes a range of infections, including acute pharyngitis (strep throat), scarlet fever, and other more serious infections such as necrotizing fasciitis. In 2019, the timeframe of the Lancet study, GAS didn’t make the list of top 33 killers. By the end of 2022 things had changed: both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) identified GAS, aka Streptococcus pyogenes, as a growing threat and issued alerts about the ominous uptick in invasive group A strep infections (iGAS).
According to the WHO, as of December 8, 2022, at least five Member States in the European Region reported an increase in iGAS. Since October 2022, 57 cases of iGAS were reported to the WHO, and children under 10 years of age represented the most affected age group. In November, the CDC was notified about a possible increase in iGAS infections at a hospital in Colorado. In the U.K. outbreak of iGAS, 15 deaths were reported.
In its Health Alert Network issued in the closing days of 2022, the CDC notified clinicians that people with current or preceding viral infections (influenza or chickenpox) are at increased risk of GAS infections. Other high-risk groups include people age 65 and over, residents of long-term care facilities, and people with underlying medical conditions. While it’s too soon to know what GAS has in store for us in 2023, it will likely capture growing attention of public health officials, health care providers, and the general public for the foreseeable future.
What are bacteria doing for us? As many readers of Germ Gems already know, an estimated 5 nonillion (5 X 10 to the 30th power) bacteria inhabit the Earth, and the human microbiome (the microbes that share our body surfaces) harbors an estimated 10 trillion bacteria. But, due to the extraordinary burst in research this century on microbiomes, we now know that only a very tiny fraction of bacterial species cause disease. Most bacterial species are either mutualists (helping themselves and their human and non-human hosts) or commensals (helping themselves but not causing disease).
Application of the huge and rapidly growing data base on the human gut microbiome is only beginning to be realized. In my December 14, 2022 Germ Gems post, “Progress in Germ Warfare: Treatment for C. diff Colitis,” I discussed the Food and Drug Administration’s recent approval of Rebyota, the first human fecal microbiota product that can prevent recurrent C. diff colitis. The hope now is that this important milestone will be followed by development of other bacterial products aimed at disorders associated with an altered gut microbiome, such as inflammatory bowel diseases, obesity, asthma, autoimmune diseases, anxiety and depression.
A scientific field that’s been nurtured by human microbiome science is the “Gut-Brain Axis” (GBA). The GBA consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions.
We are all aware of the idea of “going with your gut” in making decisions. Studies of the impacts of the GBA on human behaviors are in their infancy. However, the study “A microbiome-dependent gut–brain pathway regulates motivation for exercise” published in the journal Nature this past December is particularly intriguing.
In this study, University of Pennsylvania researchers found that the desire of mice to run in an exercise wheel was determined by two types of bacteria harbored in their gut, Eubacterium rectale and Coprococcus eutactus. The researchers traced this motivating effect to run to metabolites produced by these gut bacteria. These metabolites are known to stimulate receptors called CB1 endocannabinoid-receptors in the nervous system, which in turn causes an increase in levels of the neurotransmitter dopamine during exercise. (CB1 cannabinoid receptors are activated by psychoactive agents such as those found in marijuana, and dopamine is responsible for allowing you to feel pleasure, satisfaction, and motivation. When you feel good that you have achieved something, it is because you have a surge of dopamine in the brain.)
According to the senior author of the paper, microbiologist Christoph Thaiss, “The genetic impact on the microbiome is rather minor, but lifestyle factors strongly impact the composition of the gut microbiome.” According to a January 4, 2023 article in WebMD, Thaiss “hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.” If he finds one, sign me up for an infusion but only 3 miles please.