FAPESP Week New York

By Maria Fernanda Ziegler, in New York  |  Agência FAPESP – Despite being invisible in most cases, there are more bacteria roaming around our bodies than there are human cells. Bacteria are not just in the human body, but everywhere, thanks to their ability to develop tools and mechanisms that adapt to their needs, whether it be swimming, digesting oatmeal in someone’s stomach or becoming antibiotic resistant.

Based on this hypothesis, Nicolas Biais, an assistant professor at the City University of New York (CUNY), is trying to understand structures and mechanisms – or, as he likes to say, the superpowers – of bacteria in order to find new ways to fight diseases. He heads up the Mechanical Microbiology Laboratory at Brooklyn College, where he is studying how the pathogen that causes gonorrhea interacts with human cells.

“Years ago, Neisseria gonorrhoeae used to be a problem, especially for the Army. Luckily, penicillin was discovered. However, the bacteria have the capacity to share information and have become more resistant in recent decades, so much so that 33% of gonorrhea cases treated in U.S. hospitals are antibiotic resistant,” said Biais, in a presentation given at FAPESP Week New York.

The meeting, held at the City University of New York (CUNY) November 26-28, 2018, involved Brazilian and U.S. researchers with the aim of strengthening research partnerships.

Biais points out that in the coming years, gonorrhea may be one of the most important sexually transmitted diseases, with 100 million new cases a year worldwide. “The reason for this is that the bacteria are becoming more resistant, but every superpower also has a weakness,” he said.

One of the key elements for the formation of Neisseria gonorrhoeae microcolonies – they are rarely found alone, but instead in hubs of hundreds – is the action of retractable bacterial fibers called Type IV pili. These structures are involved in several aspects of the bacteria’s physiology, including motility, adhesion, infection, DNA uptake and biofilm formation.

In a study conducted at the University of Arizona, Biais discovered that by deactivating the molecular mechanism that governs retraction of the Type IV pili, the bacteria are rendered noninfectious.

“We found different ways of studying this mechanism, first by looking at the individual movement of each bacterium and then by seeing directly how they act together. We discovered that the ability of these small arms and their force are critical for the infection, to the extent that, if they are removed, the bacteria are no longer infectious,” he said.

The researchers also showed that the retraction in the microcolonies of N. gonorrhoeae can exert 100,000 times more force than the body weight of a single bacterium.

“Chemically they are the same, but there is no infection. When they interact with human cells, it is possible to see a chain reaction, not just chemical, but physical. However, without the force (of the pili), none of this takes place. It is as if they are giving a massage. What we are trying to understand in our laboratory is how we can have different types of massage, in other words, different ways of interacting with different hosts,” he said.

Switch off the system, from the bacteria to the cancer

Kevin Gardner, director of the Structural Biology Initiative at the Advanced Science Research Center of CUNY, is also studying the atomic structure of molecules to understand how they interact with one another and to biological activities.

On the basis of studies in structural biology, the research group led by Gardner discovered that proteins use ordinary sensory mechanisms, despite the great diversity in their functions and biological environments.

“The more we understand the biology, starting with the structure at the atomic level, the easier it will be to understand its mechanisms and functions,” Gardner said during his presentation at FAPESP Week.

One of the discoveries made by the group of researchers is that in order to survive in environments such as the ocean bottom, some bacteria need to detect light in order to adapt to changes in the environment. “This blue light detection mechanism allows them to have a sort of internal clock. At the molecular level, these processes are accomplished by a cascade of protein interactions.”

Another finding presented by Gardner is related to human cancer and its connection to oxygen sensitivity. The study analyzed solid tumors with no blood vessel growth. "However, once the tumor becomes big enough to be visible, its sensors begin to seek oxygen, finding ways to capture oxygen from the body and controlling as much as they can from blood cells,” he said.

"So, we made a small molecule that acts like a drug able to switch off the system. To our delight, this is now being tested in clinical trials in Texas. Who knows, we may have found a way to apply the science we are doing to provide treatment to a large number of patients," he said.