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The Power of Shear Flow: 5 Innovative Publications Investigating Microbial Threats

Bacterial biofilms are found throughout nature, in places such as ponds, the human body, and food. Although humans peacefully co-exist and even benefit from many types of bacteria, some strains, such as Pseudomonas aeruginosa, can form pathogenic biofilms. To combat these harmful biofilms, many researchers are engaged in investigations aimed at determining the mechanisms of antimicrobial resistance and/or discovering and developing antimicrobial materials and pharmaceuticals.

Often, the translation of the results of antimicrobial investigations to real-world scenarios is disappointing, with many materials and pharmaceuticals not living up to expectations that were set during lab experimentation. A major factor in these real-world failures is that many biofilms are investigated under static conditions, which do not represent how biofilms exist in real-world environments. Here we highlight recent, high-impact, peer-reviewed articles from scientists who improved the physiological relevance of their antimicrobial investigations by assaying biofilms under shear stress.   

1. Interspecies competition in oral biofilms mediated by Streptococcus gordonii extracellular deoxyribonuclease SsnA 

In a fascinating investigation, Rostami et al. delved into the hidden battleground within our mouths where bacteria engage in fierce competition for survival. The study focused on a specific bacterium called Streptococcus gordonii and its weapon of choice: the enzyme SsnA. By growing mixed-species biofilms under low shear flow of primary saliva, the group found that SsnA works by breaking down the DNA released by other bacteria, disrupting their ability to form biofilms and survive in the oral environment (Figure 1). This discovery sheds light on the complex interactions between different species of bacteria in our mouths and how they compete for resources and territory. Understanding these dynamics could lead to new strategies for promoting oral health and combating diseases like tooth decay and gum inflammation.

Journal: NPJ Biofilms and Microbiomes, December 2022

Interspecies competition in oral biofilms mediated by Streptococcus gordonii

Figure 1.Sucrose (0.3%) supplemented saliva was used to grow microcosm biofilms and Bacillus licheniformis extracellular nuclease NucB was included in the lower half of the growth channel. Adapted from Rostami et al. 2022. doi.org/10.1038/s41522- 022-00359-z

 

2. The combination of diethyldithiocarbamate and copper ions is active against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro and in vivo

In an exciting study by Kaul et al., consistent feeding and waste removal provided by shear flow enabled the group to grow truly mature biofilms, empowering the discovery of a powerful weapon in the fight against stubborn bacterial infections (Figure 2). Although mature biofilms formed by Staphylococcus aureus and Staphylococcus epidermidis are notorious for being tough and antibiotic-resistant, the researchers found that by combining two substances – diethyldithiocarbamate (DETC) and copper ions – they effectively destroyed these bacterial biofilms. When used together, DETC and copper ions acted like a dynamic duo, penetrating the biofilms and killing the bacteria within. This combination was effective both in laboratory tests and in live animal models, showing promise for future treatments of bacterial infections.

Journal: Frontiers in Microbiology, September 2022

The combination of diethyldithiocarbamate and copper ions is active against Staphylococcus aureus and

Figure 2. Monitoring of MRSA Mu50 biofilm formation over 24 h when left untreated or treated with a combination of 8 μg/mL diethyldithiocarbamate and 32 μg/mL Cu2+ combination (DDC-Cu2+) using the Bioflux system. Scale bar represents 50 μm. Kaul et al. 2022. doi.org/10.3389/fmicb.2022.999893

 

3. Antimicrobial activity of antibiotics on biofilm formed by Staphylococcus aureus and Pseudomonas aeruginosa in an open microfluidic model mimicking the diabetic foot environment

In an important investigation, Pouget et al. made strides in the battle against infections in diabetic foot wounds. The study focused on two troublesome bacteria commonly found in diabetic foot wounds: Staphylococcus aureus and Pseudomonas aeruginosa, which are known to create antibiotic-resistant biofilms. The group found that traditional antibiotics, while effective against these planktonic bacteria in a liquid environment, struggle to penetrate and kill the bacteria within biofilms. To address this challenge, the researchers developed a novel microfluidic model that mimics the environment of a diabetic foot wound. Using this model, they tested the antimicrobial activity of different antibiotics against biofilms formed by S. aureus and P. aeruginosa. Their findings revealed that while some antibiotics were able to partially inhibit biofilm formation, none were able to completely eradicate the biofilms. This underscores the need for new strategies to combat bacterial biofilms in diabetic foot wounds.

Journal: Journal of Antimicrobial Chemotherapy, February 2023

 

4. Porphyromonas gingivalis interaction with Candida albicans allows for aerobic escape, virulence and adherence

In a recent study, de Jongh et al. uncovered a surprising collaboration between two common microorganisms found in the mouth: Porphyromonas gingivalis, a type of bacteria, and Candida albicans, a type of fungus. Both are known to colonize the mouth and contribute to oral infections, but their interactions are not fully understood. Leveraging a microfluidic shear flow system, the group mimicked the saliva flow of the oral cavity to co-culture P. gingivalis and C. albicans (Figure 3). The researchers discovered that when these two microorganisms come into contact, they form a symbiotic relationship that enhances their ability to adhere to surfaces in the mouth and cause harm. One of the study’s key findings was that the presence of C. albicans allows P. gingivalis to thrive in oxygen-rich environments, which are normally toxic to the bacteria. This enables P. gingivalis to spread more easily in the mouth, contributing to the progression of gum disease. Their partnership, while unexpected, has profound implications for oral health and may contribute to conditions like gum disease. Overall, this research provides valuable insights into the complex interactions between microorganisms in the mouth and highlights the importance of understanding these dynamics for maintaining oral health.

Journal: Biofilms, June 2024

Porphyromonas gingivalis interaction with Candida albicans allows for aerobic escape virulence and

Figure 3. Adherence of P. gingivalis labeled with carboxyfluorescein succinimidyl ester (CFSE) to C. albicans. P. gingivalis adheres to C. albicans hyphae within 1.5 h. Scale bar indicates 25 μm in each picture. Adapted from de Jongh et al. 2024. doi.org/10.1016/j. bioflm.2023.100172

 

5. Anti-biofilm activity of murepavadin against cystic fibrosis Pseudomonas aeruginosa isolates

Recently, Díez-Aguilar et al. made what may be a significant breakthrough in the fight against infections caused by Pseudomonas aeruginosa in individuals with cystic fibrosis (CF). P. aeruginosa is a common and stubborn bacterium that can cause serious lung infections in people with CF, leading to respiratory problems and other health complications. The group examined the impact of 4 antibiotics on 53 morphotypes under both static and shear flow conditions. Although all of the tested antibiotics were effective at high concentrations, interestingly, the concentration of aztreonam required for antibiofilm activity was much lower when used under shear flow compared to static cultures. However, the researchers found that a compound called murepavadin showed the most promising anti-biofilm activity against P. aeruginosa isolates. Murepavadin penetrated the biofilms and effectively killed the bacteria, even those that were resistant to traditional antibiotics. This discovery offers hope for new treatment options for individuals with CF who are battling P. aeruginosa infections. By targeting biofilms with compounds like murepavadin, scientists may overcome the challenges posed by antibiotic resistance and improve patient outcomes.

Journal: Journal of Antimicrobial Chemotherapy, September 2021

Conclusion

Culturing and assaying bacterial biofilms under shear flow conditions not only induces changes in response to shear stress but also improves feeding and waste removal. Together, these factors enable the growth of truly mature biofilms that better represent biofilms in their natural environments. Using the totally complete, easy-to-use, cost-effective BioFlux shear flow system enabled these investigators with the ability to enhance the physiological relevance of their antimicrobial investigations. 

Learn more about BioFlux

Dr. Anson Blanks completed his BS in exercise physiology at East Carolina University in 2003. Dr. Blanks then attended Appalachian State University, where he earned his Master of Science in clinical exercise science in 2009. After working as a clinical exercise physiologist in a cardiopulmonary rehabilitation center in Washington, DC, Dr. Blanks decided to pursue a career in scientific research. He attended Virginia Commonwealth University, where he completed his Ph.D. in rehabilitation and Movement Science in 2018. After spending several years as a research and development scientist in biotechnology industry, Dr. Blanks is now a scientific marketing manager for Cell Microsystems in Durham, NC.

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