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Antibiotics Wreak Havoc On The Gut. Can We Kill The Bad Bugs And Spare The Good Ones?

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New Weakness Found In Antibiotic-resistant Pseudomonas Aeruginosa

Antibiotic resistant bacteria are experts in evolving new strategies to avoid being killed by antibiotics.

One such bacterium is Pseudomonas aeruginosa, which is naturally found in soil and water, but also hospitals, nursing homes and similar institutions for persons with weakened immune systems are home for strains of this bacterium. As many P. Aeruginosa strains found in hospitals are resistant to most antibiotics in use, science is forced to constantly search for new ways to kill them.

Now, at team of researchers from Department of Biochemistry and Molecular Biology and Department of Clinical Microbiology, University of Southern Denmark, have discovered a weakness in P. Aeruginosa with the potential to become the target for a new way to attack it. The team has published their findings in the journal Microbiology Spectrum, link https://journals.Asm.Org/doi/10.1128/spectrum.03875-23.The authors are Clare Kirkpatrick, Magnus Z. Østergaard, Flemming D. Nielsen and Mette H. Meinfeldt.

Thick and slimy biofilm

The team discovered a mechanism, that reduces the formation of biofilm on the surface of P. Aeruginosa. The formation of sticky, slimy biofilm is a powerful tool used by bacteria to protect themselves against antibiotics – a trick also used by P. Aeruginosa.

This biofilm can be so thick and gooey that antibiotic cannot penetrate the cell surface and reach its target inside the cell. Maybe one day, we could pharmacologically stimulate this mechanism to reduce biofilm development on the surface of P. Aeruginosa."

Clare Kirkpatrick, head of research at Department of Biochemistry and Molecular Biology

Three new genes

Specifically, the researchers worked with three newly discovered genes in a lab-grown strain of P. Aeruginosa. When they overexpressed these genes, they saw a strong reduction of biofilm. Of significance is that the system affected by the genes is part of the P. Aeruginosa core genome, meaning that it is universally found in all the P. Aeruginosa strains sequenced so far.

"Being part of P. Aeruginosa's core genome, this system has been found in all investigated strains of P. Aeruginosa, including a large variety of strains isolated from patients. So, there is reason to believe that reduction of biofilm via this system should be effective in all known strains of P. Aeruginosa", said Clare Kirkpatrick.

Bacteria strains can evolve individually and mutate quickly and constantly when they are under pressure. It is not uncommon for patients infected with a P. Aeruginosa strain to initially respond well to antibiotic treatment but then become resistant as the strain evolves resistance during treatment. Strains mutate, but their common core genome does not change.

Stressing the cell wall

In their experiments, the researchers activated the biofilm reducing system by overexpressing genes. But they also discovered that the system is naturally stimulated by cell wall stress.

"So, if we stress the cell wall, it may naturally lead to a reduction in biofilm, making it easier for antibiotic to penetrate the cell wall", said Clare Kirkpatrick, adding:

"Currently, cell wall-targeted drugs are not widely used against P. Aeruginosa, but perhaps, they could start to be used as additives to help reduce biofilm production and improve access of the existing antibiotics to the cells."

Bacteria cell wall is very different from human cell wall

When combating infectious bacteria, there are only a limited number of targets to attack. Targets found in both bacterial and human cells cannot be attacked, as the antibiotics would also affect human cells.

Bacterial cells and human cells have some targets in common, such as the process that replicates DNA and the processes controlling basic glucose metabolism or respiration in cells.

Among the targets unique to bacteria are various protein functions and also the bacterial cell wall is considered a suitable target, as it is very different from the human cell wall.

Source:

Journal reference:

Østergaard, M. Z., et al. (2024) The uncharacterized PA3040-3042 operon is part of the cell envelope stress response and a tobramycin resistance determinant in a clinical isolate of Pseudomonas aeruginosa. Microbiology Spectrum. Doi.Org/10.1128/spectrum.03875-23.

Why Perdue Farms Isn't Giving Up On 'no Antibiotics Ever' Chicken

After Tyson Foods said it would reintroduce some antibiotics in its chicken supply last summer, Perdue Farms is now the only of the four largest processors dedicated to "no antibiotics ever" production. And the poultry giant doesn't plan on reversing course.

"We worked hard to get successful and raise chickens the right way," Bruce Stewart-Brown, Perdue senior vice president of technical services and innovation, told Agriculture Dive in an interview. "And it has taken us to a position on animal welfare and animal care that we're pretty proud of."

Perdue remains a standout in the chicken industry as the sector is poised to move backwards on the issue. Although antibiotic sales for chicken declined for 2022, that trend could change after Tyson — the largest producer in the U.S. — walked back some of its antibiotic-free pledges last year. The move has already had ripple effects across food supply chains, with Chick-fil-A dropping its pledge to only serve antibiotic-free chicken in March due to sourcing concerns.   

The agriculture industry has traditionally relied on antibiotics as a low-cost method to boost animal growth and control disease for livestock raised in sometimes crowded and unsanitary spaces. However, an overuse of antibiotics in animals has been found to raise the risk of antibacterial resistance in people, making human medications less effective. 

"Wasting a cornerstone of modern medicine to compensate for poor animal husbandry, for the sake of slightly cheaper chicken is foolish," Andre Delattre, chief operating officer of environmental and consumer advocacy organization Public Interest Research Group, told Agriculture Dive in an email. "Perdue deserves credit for sticking with its NAE commitment as others are backing away."

Taking antibiotics out of production is expensive and sometimes difficult work, Stewart-Brown said, requiring that farmers constantly ensure their flocks are in pristine environments to prevent any potential contamination. Perdue began its journey toward antibiotic-free production in 2002, well over a decade before competitors like Tyson and Pilgrim's Pride unveiled their pledges to reduce use of the drugs.

At the time, Perdue was responding to animal welfare complaints from consumers, with concerns mounting that meat producers were indiscriminately throwing antibiotics into feed in order to keep animals alive despite crowded and often unsanitary conditions. Over the course of 12 years, Perdue phased out drugs important to human medicines, first in animal feed in 2007 and then in hatcheries in 2014.

"We went through the process the right way, taking it a little bit at a time to really think through all aspects of raising chickens," Stewart-Brown said. 

In 2016, the company went even further, saying it would end use of animal-only antibiotics, including ionophores, which are commonly used to control the common parasitic intestinal disease coccidiosis in poultry. Instead of antibiotics, Perdue relies on natural supplements, such as oregano and thyme, to promote gut health in chickens.

As Perdue began to remove antibiotics from its production process, not all of its farmers were on board. Some growers left because of the additional steps needed to ensure operations are "super clean," Stewart-Brown said.

"It did change the farmer's perspective on how tough their job was," Stewart-Brown said. "Some of them were unhappy and decided they'd rather raise chickens for another company, which we thought was probably a good idea."

However, the move toward antibiotic-free production also attracted new growers who were more aligned with Perdue's goals. Now, Perdue only uses antibiotics to treat chickens when they fall ill, which occurs around 5% a year on average. Chickens treated with antibiotics are removed from the no antibiotics ever program and sold through other channels.

The transition away from antibiotics hasn't had a major impact on disease spread within Perdue's flocks, with the percentage of chickens treated with medications trending down over the years. It's also brought environmental benefits, preventing antibiotics from entering and contaminating groundwater. 

The combination of environmental, animal welfare and public health benefits from removing medicines in animal production continues to drive Perdue's no antibiotics ever commitment.

"All that cleaning, it's not just about no antibiotics ever. It's about better health for animals, humans and the environment," Stewart-Brown said. "There's all kinds of good things that come from that so we can't back down."

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