As for the old remedies for new health challenges

Nov 21, 2019 | | Say something

The last thing someone wants during a hospital stay is an infection acquired in the hospital. Nosocomial infections, as they are called, are on the rise as more pathogens become resistant to currently available medications. A pathogen tops the list as one of the most common, one of the most fatal and one of the most difficult to treat: Acinetobacter baumannii.

Kumar Venkitanarayanan, Associate Dean of Research and Postgraduate Studies, and professor at the Faculty of Agriculture, Health and Natural Resources, and his team recently published an investigation in the journal. Wound medicine detailing how they are working to change that.

A. baumannii It is included in the ESKAPE list of the World Health Organization, a collection of bacteria that are becoming increasingly resistant to antibiotics. With the increase in resistance, the investigation of alternative therapies is paramount and, in some cases, returning to old therapies is proving to be effective.

Infections of A. baumannii They are especially difficult to treat since bacteria have an arsenal of measures to acquire resistance to antibiotics, says Venkitanarayanan. Bacteria are also capable of forming biofilms that strengthen the infection against antibiotics and give them a greater chance of spreading, especially in hospital settings.

"A. baumannii It is primarily a nosocomial pathogen that especially affects people with compromised immune systems, the very young, the very old, the burn victims, and it is also reported in the wounds of combat soldiers, "says Venkitanarayanan. A. baumannii It can infect wounds and cause especially persistent infections of the skin and soft tissues and eventually spread, causing systemic infections that are difficult and sometimes impossible to treat, such as pneumonia or urinary tract infections.

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Instead of adopting the approach of developing new antibiotics, the Venkitanarayanan research group looks for older treatment methods to look for new strategies.

"In ancient times, metals were used as antimicrobial treatments, so we decided to revisit them to see if they could be applied to modern treatments," says Venkitanarayanan.

Metals and metalloids have long been recognized for their disinfectant qualities and, as such, have been used in food preservation, water disinfection, cleaning products and for wound treatment. The researchers examined the metals for their antimicrobial efficacy and found that selenium, a metalloid, is promising. In addition to possible antimicrobial uses, selenium is also an important micronutrient in the functioning of the immune system, nucleic acid synthesis and other physiological processes.

The researchers first determined the minimum amount of selenium needed to inhibit the virulence of the bacteria or the ability to cause disease. With this approach, Venkitanarayanan says that bacteria can still grow, but cannot infect the host so effectively.

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Since bacteria develop resistance to drugs when their survival is affected, at sub-lethal antivirulence concentrations, bacteria are less likely to develop resistance to antibiotics. In addition, at these levels, medications are less likely to have a negative impact on the patient, for example, such as what is seen with antibiotics in which the treatment affects the host's microbiome.

Then, the team simulated a wound by culturing cells and wound fluids in a model matrix. The wound matrix model was then inoculated with the bacteria, with or without the amount of selenium needed to inhibit A. baumannii virulence.

Biofilms treated with or without scanning electron microscopes were observed, and DNA analysis was performed to assess whether genetic changes occurred after exposure to selenium.

The researchers also conducted tests to determine how effectively bacteria could adhere and invade skin cells with and without selenium present.

Bacteria can use different strategies to colonize a host, from thick coatings to prevent drying or penetration of drugs, to the means to adhere and reach the host. It seems that selenium has ways to dismantle multiple strategies in A. baumannii.

What the researchers found was that for crops exposed to selenium, the biofilm architecture of those crops decreased significantly, leaving the biofilm to look diffuse and decompose. Consequently, post-treatment genetic analysis revealed a low significant regulation of genes associated with biofilm production. Selenium also reduced the bacterial ability to adhere and invade skin cells.

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"There is no clear data on how selenium works. There seems to be toxicity against the outer membrane of the bacteria and it could also cause toxicity against DNA, potentially in genes that are involved in the creation of biofilms," says Venkitanarayanan.

Studying these exact mechanisms are the next steps that researchers will take, getting a little closer to clinical applications.

Although the exact mechanisms of action for selenium are not known at this time, Venkitanarayanan says it is important to explore these types of options. His group has explored the efficacy of selenium to treat other infections such as enterohemorrhagic Escherichia coli (EHEC) and Clostridium difficile (C. diff) As more resistance to antibiotics is found in the treatment of various bacterial infections, Venkitanarayanan says it is important to look back at the treatments that once worked.

"Even if we use the old methods together with modern antibiotics, it is better than not being able to use anything."

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. (tagsToTranslate) Biology (t) Bacteriology (t) Microbiology (t) Medicine / Health

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