Our Life and Death Relationship with Bacteria

We have a symbiotic relationship with bacteria. Many are essential for life, but a few can be lethal. Plus, the bacteria play an essential role in returning us to dust. As lab rats, we need to be very careful to manage bacteria and especially antibiotics. It seems that our ability to predict if a new compound will have antibiotic properties is low. Failure to manage our microbiome can have severe, long-term consequences. We best be careful!

Let’s look at some data points.

Carl Zimmer, writing in a recent New York Times Science section,1 points out that our microbiome is perhaps our own best source of medicine. This is based on a paper by Michael A. Fischbach of UCSF reporting on an analysis of the microbiomes of 242 healthy volunteers as part of the Human Microbiome Project.2 They found 14,000 bacterial gene clusters (BGCs) residing in 2340 microbes. These genes produced 3118 natural products (NPs) conserved across the 242 human cohort. Most of the genes and associated natural products were novel. Since the NPs are conserved across the cohort, they probably have important biological function. For example, they purified lactocillin from vaginal microbiota and determined its structure. It has potent antibacterial activity against gram-positive vaginal pathogens. The abstract concludes, “Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans.”

The microbiome is a very competitive environment. Some of the NPs are expected to be selective antibiotics that our body relies upon for homeostasis. Others are probably involved in intermicrobe signaling, and still others in the regulation of metabolism through proteases, kinases and inhibitors.

Antibiotics have life-long effects

Two of my progeny have obvious weight problems. While perusing a recent issue of Cell, I noticed a report, “Altering the intestinal microbiota during a critical development window has lasting metabolic consequences.”3 Essentially, exposing infants to low-dose penicillin amplifies diet-induced obesity. Early perturbation of the microbiome leads to long-term increase in adiposity, especially with a high fat diet. The growth promotion phenotype is transferable to germ-free hosts by LDP-selected microbiota. This shows that the microbiota, and not the antibiotics, are the causal agent. My wife had trouble with breast infections immediately after childbirth. Antibiotics were administered, and our children probably were exposed while nursing.

I recall another report that babies delivered by C-section have lower resistance to infection than babies delivered vaginally. This was attributed to direct inoculation of the baby from the mother’s digestive tract. On one level, this sounds gross, but I have no trouble seeing how inoculation could happen, especially in a natural (nonsterile) environment. Natural selection in humans has probably evolved to allow them to tolerate and possibly even benefit from early population of the digestive tract.

Ranchers have long known that low doses of antibiotics in feed accelerate weight gain. Could low levels of antibiotics in our food be a contributing factor to America’s obesity epidemic? Residual levels in our food seem low, but bioaccumulation of these substances is real. There is evidence that this happens in mice.4

Effects of bacteria in the lab

Okay, so bacteria are essential for homeostasis. How does this affect us in our labs? Let’s start with eliminating cross-contamination of samples. The work environment needs to be compatible with the workflow of the experiment. Common operations such as weighing need to be controlled. Pipetting is another concern, especially during aspiration. Tips with aspiration guards are available. Systematic labeling of vials is essential. Then samples need to be managed with biobanking software. Disposal is still another issue that must be addressed.

However, since we are often dealing with compounds with an unknown structure and purpose, one needs to be careful to protect laboratory staff. Some lab rats seem to ignore the potential toxicity or other biological function of NPs. But would you expect ricin to be toxic based upon its structure and origin? Castor plants are common, and the structure resembles other two-unit proteins. Nothing in ricin’s structure jumps out at me. Yet it kills by inhibiting protein synthesis.

Hand washing is probably the best precaution, but with what? This is not a simple topic since the technology is evolving. First, we do not know much about our microbiome. Thus we should reduce exposure risks for microbes including fungi by using biological safety hoods along with gloving. This is just good laboratory practice. If you know that the experiment or screen involves virulent agents, you need to work in an environment designed for the purpose.

Microbes are living things, so if in doubt they should be disposed of as a biohazard. The following discusses safety precautions that can be taken in the lab to protect against bacteria and microbes.

Personal safety

Keeping homeostasis

Protecting you and your colleagues is essential. If you are well, then, it is worth developing habits to keep you that way. Plus, I personally feel an obligation to avoid being a bioreactor for resistant bacteria. I know that every time I take an antibiotic, I kill off many good bacteria, and hopefully the bad ones also. The drugs have a different spectrum of action. I’d hate to encourage development of more virulent strains. Always ask yourself if taking the antibiotic is necessary. If it is, then take it all, as prescribed! Through natural selection, misusing antibiotics can favor development of antibiotic-resistant strains, aka “super bugs,” including MRSA. Super bugs are much more difficult therapeutic targets.

Gloving

Gloving is probably the most effective way to reduce contamination risk to staff and other samples. Gloves are awkward, hot, and produce lots of lab waste. But if the risk is significant, then gloving is required.

Hand washing

In healthcare environments, hand washing is a major focus. GE Healthcare even has an IT program (Hand Hygiene Compliance Monitoring Solution) to monitor and report hand washing for all staff.5 Although hand hygiene is designed to reduce hospital-acquired infections (HAI), it is applicable to R&D labs also.

What should you wash with? The answer is not clear. Richard Besser, M.D., of ABC News reported in September 2014 that hand washing reduced bacteria counts by more than 99%. Most of the reduction was attributed to mechanical action. Antibacterial soap did not reduce the residual bacterial level.

In December 2013, the FDA announced an investigation of antibacterial soap.6 The science and claims seem to be inconsistent. Plus, consistent exposure of bacteria to the low levels of antibiotic present in these soaps helps them build resistance by natural selection. This is not in our interest.

Until the FDA completes the study, one should be cautious about general-purpose antibiotics. Phisohex (hexachlorophene), which used triclosan as an antimicrobial agent, is one example of a widely used product that had unintended consequences (Sanofi -Aventis discontinued production of Phisohex in September 2013.) Triclosan is also suspected to have hormonal action as it moves transdermally into our body. To think that I used to apply it liberally to the skin of my wife and infants.

Hand sanitizers

Hand sanitizers are seen as an alternative and occasionally a supplement to hand washing. There are several types, including formulations of alcohols (usually ethanol and propanol), quaternary amines (usually benzalkonium chloride), or chlorinated phenols (triclosan, for example). Their efficacy depends upon the target microbe. A quick review of Wikipedia presents a confusing picture.7 For example, some correspondents report that hand sanitizers reduce bacterial counts more effectively than hand washing, while others claim thathand washing is preferred. Hand sanitizers require that the skin be clean before the sanitizer is applied.

Sanitizers are not a substitute for hand washing after relieving oneself. (See the CDC poster in Ref.8 for details.) Typhoid Mary comes to mind. She spread typhoid fever, which is different from typhus, which is transmitted by rats and ticks. It seems that achieving cleanliness may depend on the tenacity of the microorgansim and how thoroughly an individual washes.

Summary

Bacteria and other microbes are part of our lives. Their diversity and evolution present special problems for each of us. By following the research on our microbiome, we will have an opportunity to improve our lives. Ignore the microbiome at your peril.

References

  1. Zimmer, C. We may be our own best medicine. The New York Times, Sept 17, 2014, p D3.
  2. Donia, M.S.; Cimermancic, P. et al. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell Sept 2014, 158(6), 1402–14.
  3. Cox, L.M.; Yamanishi, S. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell Aug 2014, 158(4), 705–21.
  4. http://www.scientificamerican.com/article/antibiotics-linked-weight-gain-mice
  5. http://www3.gehealthcare.com/en/services/portfolio/handhygiene-compliancemonitoring
  6. http://www.fda.gov/forconsumers/consumerupdates/ucm378393.htm
  7. http://en.wikipedia.org/wiki/Hand_sanitizer
  8. http://www.cdc.gov/handwashing/posters.html

Robert L. Stevenson, Ph.D., is Editor, American Laboratory/Labcompare; e-mail: [email protected].