The art of escaping one’s immune system: A portrait of the bug S. aureus

Humans have developed an intricate arrangement of immune defense processes that keep invasive germs at bay. Our defense guardians, aka the innate and acquired immune systems, are relentless experts in shooting antimicrobial molecules that target the intruders. As you can imagine, our bodies allocate a decent amount of energy to defeat these invisible creatures before the invasion gets out of control. Yet, even though we are equipped with an impressive artillery, the presence of hazardous germs in our bodies still alarms us – and not just the general public, but scientists alike. While the non-specialists want to avoid germs largely due to the misconception that all microbes are bad and pose nasty threats, the scientists have a more substantive reason: the famous superbugs, including multi-resistant bacteria. These germs have been happily spreading and sadly causing loss of life and massive financial health care expenditures across the globe. With the overuse of antibiotics playing a role in this crisis, how do we reverse this reality? Let’s bring a troubling little fellow to the spotlight: Staphylococcus aureus. It’s a bug that is perhaps most troubling for sometimes developing resistance to methicillin and other frontline drugs, thus turning into the scary superbug known as methicillin-resistant Staphylococcus aureus (MRSA).

S. aureus is present in the nose and the skin flora – or microbiota, scientifically speaking – of about 30% of healthy humans. So, there’s no reason to panic. Just like many other microbes, this specific bug is opportunistic and will shift to a pathogenic state only when its surrounding environment, at a molecular level, is favorable. The will to survive is a shared trait among the living after all, and fundamental science is needed to halt the spread of these troublemakers when infection kicks in.

In fact, what is somehow curious about S. aureus is its capacity of adaptation. Against an invasion, and to prevent the bacteria growth, the innate immunity will deploy an arsenal of antimicrobial effectors such as reactive oxygen species, which damage nucleic acids, proteins and lipids, and release chelating agents such as calprotectin or lactoferrin, which sequester essential metal ions, e.g. iron, manganese or zinc. These ions are undeniably required for both bacterial survival/virulence and our immune defenses. For that reason, an attractive strategy to control an infection is limiting metal bioavailability by using molecules that bond strongly to these chemical elements in order to impede bacteria’s access to them. Such a strategy aims to dysregulate the bacteria’s physiology, thus leading to their death. This may sound like a clever strategy, but despite undergoing metal starvation, S. aureus can still successfully thrive within humans, indicating its incredible capacity to overcome exogenous local disturbances – that is, disturbances caused by external forces. Such a damn invisible ploy! This trait puzzles scientists, my lab in particular, and it pushes us to further investigate and understand the mechanisms these microbes put in place to survive in hostile environments. One of the mechanisms we study relates to how small RNAs regulate metal homeostasis and the interconnected oxidative stress responses in S. aureus – that is, how they overcome the lack of the metal ion in their surroundings and continue to multiply freely.

Bacterial cycles are short in time. For S. aureus, the population doubles every 30 minutes when a rich culturing media is available. You can imagine that new evasion strategies are developed and passed on to the next generation while you, for example, naively enjoy a cup of coffee with friends. By now, no need to stress the fact that finding more efficient ways to control S. aureus infections is going to be a splendid scientific discovery. Pulling the urgency string yet?

I am David Lalaouna and I am a CNRS researcher affiliated with the Institut de Biologie Moléculaire et Cellulaire under the laboratory of Dr Pascale Romby at the University of Strasbourg in France. The research work described above was partially funded by the Marie Skłodowska-Curie Actions (MSCA) and Grant Agreement No. 753137-SaRNAReg.

For the science lovers looking for savory details: Lalaouna D. et al., RsaC sRNA modulates the oxidative stress response of Staphylococcus aureus during manganese starvation, Nucleic Acids Research, 2019.


Mixed Media

Text by Fernanda Haffner

Illustration by Marion Couturier