Beyond good and evil: Antibiotics don’t fully solve the problem of two-faced germs

Antibiotics. Vaccines. Good sanitation. Get rid of the germs, and we prevent infection and illness, right? That’s been a guiding principle of medicine and public health for 150+ years (Just ask Semmelweis or Pasteur).

But we are covered in germs. Many are good for our health: they train our immune systems, and having the right balance of species may affect our brain function and protect us from cancers, obesity, and – crucially – infections from more sinister bugs.

As a result, we’ve developed this idea of good and bad microbes. The ones that live on us are the good germs, and the ones that make us sick are the bad germs. Except it’s not that simple. In many cases, the “good” and the “bad” are closely related strains, or even flip sides of the same organism.

Beta hemolysis on blood agar

This petri dish is nice and all, but we’d rather live in people. (S. agalactiae, better known as Group B Strep, making the donut-shaped smaller colonies. Photo by HansN)

Group B Strep is a major cause of sepsis, pneumonia, and meningitis in newborns. Bad germ. But it lives harmlessly in perhaps 25% of women, where it inhabits their intestines and sometimes hops over to the vagina. People with that bacterium, formally called Streptococcus agalactiae, aren’t said to be “infected” if they’re not sick; rather, they are “colonized.” A colonized mother has a 50% chance of passing the germ to her child, who would then also be colonized. This isn’t a problem.

But in some cases, S. agalactiae can truly infect the newborn. Even when the mother is GBS-positive, it is rare, but this is the reason for (in some countries, including the US) routine GBS testing in late pregnancy, and antibiotics given during labor. The antibiotics blast away much of the bacteria the child could come in contact with, good and bad. Antibiotic treament reduces GBS infection, so it has been called a success; on the other hand, there is no evidence to show an effect on all-cause mortality. It’s possible that killing the good bacteria leaves the baby vulnerable to infection from its environment. (We already know, from comparing vaginally-born to c-section babies, that exposure to vaginal bacteria makes a difference in the baby’s microbiome. We don’t know, yet, how big a difference that makes to their later health.)

Helicobacter pylori

I’ll keep you thin and healthy, and only give you a leeetle bit of stomach cancer… (H. pylori image by AJ Cann)

Or take Helicobacter pylori, the corkscrew-shaped bacterium that causes ulcers and stomach cancer. It was revolutionary when Barry Marshall proved that ulcers were caused by bacteria and not stress, by drinking a vial of H. pylori, waiting until he developed symptoms of gastritis, and culturing the creature from his stomach. Today, Marshall and his pathologist partner Robin Warren have a Nobel Prize, ulcers are treated with antibiotics, and stomach cancer is rare.

But H. pylori is not all bad, either. Marshall himself told Discover magazine, “We’re pretty certain now that by the start of the 20th century, 100 percent of mankind was [colonized] with Helicobacter pylori, but you can go through your whole life and never have any symptoms.”

In fact, people who harbor this bug are less likely to develop allergies and asthma, and they circulate more ghrelin, an anti-hunger hormone, possibly combating obesity. H. pylori is on the decline, though; the bacteria that accompanied humans through our radiation out of Africa are no longer able to gain a foothold in children’s stomachs. The reasons may include clean water, c-sections, and antibiotics.

Streptococcus pneumoniae-263

Hi, can we live in your nose? We promise we won’t cause any trouble… (Photo of S. pneumoniae by Janice Haney Carr)

An interesting paper came out last week about another two-faced bacterium, Streptococcus pneumoniae, better known in public-health circles as pneumococcus. It’s a major cause of pneumonia (of course), ear infections, and meningitis in children, and there’s even a vaccine against several of the most notorious serotypes. (Like HPV, pneumococcus comes in 80+ flavors, some more concerning than others.) But – and you knew I was going to say this – most of the time it’s harmless. Around ten percent of adults carry it in the mucus linings of our nose and throat; among children, the number is as high as 40%.

This new research on S. pneumoniae is directly addressing its two-faced nature: how does a good germ go bad? Anders Hakansson’s team in Buffalo grew the germs in vitro and in mice, and found a number of triggers that made them go rogue. One is high temperature, like you might find in a feverish body; another is a stress hormone. In other words, the triggers come direct from their human (or mouse) host, as the host responds to, perhaps, a viral infection. S. pneumoniae recognizes that its environment has changed, and a different survival strategy is in order. It switches on virulence genes, and makes its escape.

This explains why pneumococcus disease tends to follow viral infections, and confirms that the bacterium is normally harmless. Since fever is a trigger, one option for preventing pneumococcal disease could be to reduce patients’ temperature during viral illnesses – but fever is often protective. Allowing a fever to run its course leads to better outcomes in many cases.

Although pneumococcus vaccines are available, it’s possible that killing off one strain of the bacterium just opens doors for another. We’ve seen decline in disease rates from the strains targeted by the vaccine, but at the same time, infections from the other serotypes have increased.

Instead, a better approach might be to target S. pneumoniae‘s virulence factors directly: allow the germ to live, but attack only the individuals that are causing trouble. We’ve come a long way since the days of Pasteur, and we now know that good germs can turn bad, and bad germs can do good. In modern, microbiome-informed medicine, it’s time to move beyond good and evil.


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2 Responses to Beyond good and evil: Antibiotics don’t fully solve the problem of two-faced germs

  1. Pingback: Who’s afraid of GBS? | SciencePlug

  2. The ability of germs/bacteria to “cross-over” as it were is an often overlooked factor in modern medicine. Hopefully proper education will help spread the word that spreading around the “good” bacteria may not always be a good idea in the long run.

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