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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Australian Researchers Discover New Form of Antimicrobial Resistance in Findings That Have Implications for Microbiology Laboratories

Study findings could lead to new biomarker targets for clinical laboratories working to identify AMR bacteria

Reducing and managing antimicrobial resistance (AMR) is a major goal of researchers and health systems across the globe. And it is the job of microbiologists and clinical laboratories to identify microbes that are AMR and those which are not to guide physicians as to the most appropriate therapies for patients with bacterial infections.

Thus, a recent discovery by researchers at the Wesfarmers Centre of Vaccines and Infectious Diseases, a division of the Telethon Kids Institute at Perth Children’s Hospital in Australia, will be of interest to medical laboratory leaders. The researchers may have learned how some bacteria dodge antibiotics in the human body. Their findings could lead to new diagnostics and better patient outcomes. 

The scientists published their findings in the journal Nature Communications titled, “Host-Dependent Resistance of Group A Streptococcus to Sulfamethoxazole Mediated by a Horizontally-Acquired Reduced Folate Transporter.”

Timothy Barnett, PhD

“AMR is a silent pandemic of much greater risk to society than COVID-19. In addition to 10 million deaths per year by 2050, the WHO estimates AMR will cost the global economy $100 trillion if we can’t find a way to combat antibiotic failure,” Timothy Barnett, PhD (above), Deputy Director and head of the Strep A Pathogenesis and Diagnostics team at Wesfarmers Centre of Vaccines and Infectious Diseases, told News Medical. Additional research may provide new targets for clinical laboratories tasked with identifying antimicrobial resistant bacteria. (Photo copyright: University of Western Australia.)

Rendering an Antibiotic Ineffective

According to the University of Oxford, about 1.2 million people died worldwide in 2019 due to AMR, and antimicrobial-resistant infections played a role in as many as 4.95 million deaths that same year. The World Health Organization (WHO) declared AMR one of the top ten global public health threats facing humanity.

While investigating antibiotic sensitivity of Group A Streptococcus—a potentially deadly bacteria often detected on the skin and in the throat—the Australian researchers uncovered a mechanism that enabled bacteria to absorb nutrients from their human host and evade the antibiotic sulfamethoxazole, a commonly-prescribed treatment for Group A Strep.

“Bacteria need to make their own folates to grow and, in turn, cause disease. Some antibiotics work by blocking this folate production to stop bacteria growing and treat the infection,” Timothy Barnett, PhD, Deputy Director of the Wesfarmers Centre of Vaccines and Infectious Diseases and head of the Strep A Pathogenesis and Diagnostics team, told News Medical.

“When looking at an antibiotic commonly prescribed to treat Group A Strep skin infections, we found a mechanism of resistance where, for the first time ever, the bacteria demonstrated the ability to take folates directly from its human host when blocked from producing their own. This makes the antibiotic ineffective and the infection would likely worsen when the patient should be getting better,” he added.

According to their study, the researchers identified an energy-coupling (ECF) factor transporter S component gene that allows Group A Strep to acquire extracellular reduced folate compounds that likely “expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole.”

The study indicates that this new form of antibiotic resistance is indistinguishable under traditional testing used in microbiology and clinical laboratories, which in turn makes it difficult for clinicians to prescribe effective antibiotics to fight an infection. 

Understanding AMR before It Is Too Late

The research suggests that understanding AMR is more complicated and intricate than previously thought. Barnett and his team believe their discovery is just the “tip of the iceberg” and that it will prove to be a far-reaching issue across other bacterial pathogens in addition to Group A Strep.

In “CDC Ranks Two More Drug-Resistant Microbes as ‘Urgent Threat’ to Americans; Clinical Laboratories Are Advised to Increase Awareness of Antimicrobial Resistance,” Dark Daily covered a report by the federal Centers for Disease Control and Prevention (CDC) that calls attention the emergence of new antibiotic-resistant bacteria and fungi. In its report, the CDC lists 18 bacteria and fungi that pose either urgent, serious, or concerning threats to humans. It also placed one fungus and two bacteria on a “watch” list.

“Without antibiotics, we face a world where there will be no way to stop deadly infections, cancer patients won’t be able to have chemotherapy and people won’t have access to have life-saving surgeries,” Barnett told News Medical. “In order to preserve the long-term efficacy of antibiotics, we need to further identify and understand new mechanisms of antibiotic resistance, which will aid in the discovery of new antibiotics and allow us to monitor AMR as it arises.”

More research and clinical studies are needed before this discovery can become technology that clinical laboratories can use to test if microbes are AMR. The scientists at Wesfarmers Centre of Vaccines and Infectious Diseases are now developing testing methods to detect the presence of the antibiotic resistant mechanism and determine the best treatment options.

“It is vital we stay one step ahead of the challenges of AMR and, as researchers, we should continue to explore how resistance develops in pathogens and design rapid accurate diagnostic methods and therapeutics,” Kalindu Rodrigo, a PhD student in the Barnett lab and one of the authors of the study told News Medical. “On the other hand, equal efforts should be taken at all levels of the society including patients, health professionals, and policymakers to help reduce the impacts of AMR.”

JP Schlingman

Related Information:

Australian Researchers Unearth a New Form of Antimicrobial Resistance

New Antimicrobial Resistance Mechanism Discovered in Streptococci

Host-dependent Resistance of Group A Streptococcus to Sulfamethoxazole Mediated by a Horizontally-acquired Reduced Folate Transporter

WHO: Antimicrobial Resistance

An Estimated 1.2 Million People Died in 2019 from Antibiotic-resistant Bacterial Infections

CDC Ranks Two More Drug-Resistant Microbes as ‘Urgent Threat’ to Americans; Clinical Laboratories Are Advised to Increase Awareness of Antimicrobial Resistance

Mayo Clinic Researchers Find Some Bacteria Derail Weight Loss, Suggest Analysis of Individuals’ Microbiomes; a Clinical Lab Test Could Help Millions Fight Obesity

CDC reports more than 93-million US adults are obese, and health issues related to obesity include heart disease, stroke, type 2 diabetes, and cancers

In recent years, the role of the human microbiome in weight loss or weight gain has been studied by different research groups. There is keen interest in this subject because of the high rates of obesity, and diagnostic companies know that development of a clinical laboratory test that could assess how an individual’s microbiome affects his/her weight would be a high-demand test.

This is true of a study published this year in Mayo Clinic Proceedings. Researchers at Mayo Clinic looked at obese patients who were in an active lifestyle intervention program designed to help them lose weight. It was determined that gut microbiota can have a role in both hindering weight loss and supporting weight loss.

Gut Microbiota More Complicated than Previously Thought

The Mayo researchers determined “an increased abundance of Phascolarctobacterium was associated with [successful weight loss]. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to [lose] body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.”

How do bacteria impede weight loss? Vandana Nehra, MD, Mayo Clinic Gastroenterologist and co-senior author of the study, explained in a news  release.

“Gut bacteria have the capacity to break down complex food particles, which provides us with additional energy. And this is normally is good for us,” she says. “However, for some individuals trying to lose weight, this process may become a hindrance.”

Put another away: people who more effectively metabolized carbohydrates were the ones who struggled to drop the pounds, New Atlas pointed out.

Vandana Nehra, MD (left), and Purna Kashyap, MBBS (right), are Mayo Clinic Gastroenterologists and co-senior authors of the Mayo study. “While we need to replicate these findings in a bigger study, we now have an important direction to pursue in terms of potentially providing more individualized strategies for people who struggle with obesity,” Nehra noted in the news release. Thus, precision medicine therapy for obese individuals could be based on Mayo Clinic’s research. (Photo copyright: Mayo Clinic.)

Mayo Study Provides Clues to Microbiota Potential in Weight Loss

The Mayo researchers wanted to know how gut bacteria behave in people who are trying to lose weight.

They recruited 26 people, ranging in age from 18 to 65, from the Mayo Clinic Obesity Treatment Research Program. Fecal stool samples, for researchers’ analysis, were collected from participants at the start of the three-month study period and at the end.  The definition of successful weight loss was at least 5% of body weight.

Researchers found the following, according Live Science:

  • 2 lbs. lost, on average, among all participants;
  • Nine people were successful, losing an average of 17.4 lbs.;
  • 17 people did not meet the goal, losing on average just 3.3 lbs.; and,
  • More gut bacterial genes that break down carbohydrates were found in stool samples of the unsuccessful weight loss group, as compared to the successful dieters.

The researchers concluded that “An increased abundance of microbial genes encoding carbohydrate-active enzyme pathways and a decreased abundance of Phascolarctobacterium in the gut microbiota of obese and overweight individuals are associated with failure to lose at least 5% weight following a 3-month comprehensive lifestyle intervention program.”

Purna Kashyap, MBBS, Mayo Clinic Gastroenterologist and co-senior author of the study, told Live Science, “The study suggests there is a need to take the microbiome into account in clinical studies (on weight loss), and it also provides an important direction to pursue in terms of providing individualized care in obesity.” The very basis of precision medicine.

Future Weight-Loss Plans Based on Patient’s Microbiota

The Mayo Clinic researchers acknowledged the small sample size and need for more studies with larger samples over a longer time period. They also noted in their paper that Dialister has been associated with oral infections, such as gingivitis, and its role in energy expenditure and metabolism is unclear.

Still, the study suggests that it may soon be possible to give people individualized weight loss plans based on their gut bacteria. Clinical laboratory professionals and pathologists will want to stay abreast of follow-up studies and replication of findings by other research teams. A future medical laboratory test to analyze patients’ microbiomes could help obese people worldwide as well as lab business volume.

—Donna Marie Pocius

Related Information:

Gut Microbial Carbohydrate Metabolism Hinders Weight Loss in Overweight Adults Undergoing Lifestyle Intervention with a Volumetric Diet

Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

CDC: Adult Obesity Facts

Makeup of an Individual’s Gut Bacteria May Play Role in Weight Loss, Mayo Study Suggests

Struggle to Lose Weight? Your gut Bacteria May Be to Blame

Your Gut Bacteria May Make It Harder to Lose Weight

Diet Hit a Snag? Your Gut Bacteria May be Partly to Blame

Can’t Lose Weight? Your Gut Bacteria Could be to Blame, According to Study

Richness of Human Gut Microbiome Correlates with Metabolic Markers

Annual Medical Spending Attributable to Obesity: Payer- and Service-Specific Estimates

5 Ways Gut Bacteria Affect Your Health

Cornell Researchers Identify Gut Microbes That May Help Some People Remain Thin; Findings Could Result in Clinical Laboratory Tests to Analyze Microbiomes of Individuals

Clinical Laboratories Might Soon be Diagnosing Obesity and Guiding Therapies that Utilize Engineered Microbes

J. Craig Venter Joins Race to Crack the Puzzle of Human Aging with New Company That Aims to Sequence 100,000 Human Genomes Yearly

Big Data will play major role as Venter’s team sets out to build world’s largest database of human genotypes, microbiomes and phenotypes

For the second time in recent months, another prominent figure has declared his intention to crack the code of human aging. This time it is scientist and entrepreneur J. Craig Venter, Ph.D., known for his role in sequencing the first whole human genome.

Venter will pursue this goal through a brand new company he launched, called Human Longevity, Inc. (HLI), based in La Jolla, California.

Human Longevity, Inc. Will Compete Against Calico

This is a noteworthy development. Pathologists and clinical laboratory managers already know Venter’s competition in this race is a company called Calico that was founded by several entrepreneurs linked to Google. (more…)

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