Saturday, 30 November 2019

Transient and long-term disruption of gut microbes after antibiotics

Trillions of microbes in the intestine aid human health, including digestion of breast milk, breaking down fiber and helping control the immune system. However, antibiotic treatment is known to disrupt the community structure of these microbes -- 500 to 1,000 bacterial species that have a mainly beneficial influence.

A study at the University of Alabama at Birmingham now has tracked this disruption at the level of a strain of microbes replacing another strain of the same species in 30 individuals -- all of them young, healthy adults who would be expected to have stable microbial communities.
The UAB study used bioinformatic tools to analyze a previously described study of 18 individuals who had been given a single antibiotic, cefprozil, for a week. Their fecal samples were collected at pre-treatment, at the end of antibiotic treatment and at three months post-treatment. The UAB study also analyzed previously described data of 12 individuals who were given a combination of three antibiotics -- meropenem, gentamicin and vancomycin -- for four days. Their fecal samples were collected at pretreatment; at end of treatment; and at four, 38 and 176 days post-treatment. Six control individuals who did not receive antibiotics were also analyzed.

In general, the UAB researchers found that strains of the 10 most abundant species remained stable in controls. In the single antibiotic treatment individuals, 15 of 18 individuals had transient new strains post-treatment that, in turn, were replaced by the original strain by three months post-treatment.

In contrast, the triple-antibiotics individuals showed a significant increase of new strains that persisted as long as six months after treatment, as compared to the single antibiotic and the control individuals. Furthermore, the fraction of transient strains was also significantly higher in the multiple antibiotics individuals. This suggested a long-term change to an alternative stable microbiome state, Morrow says. These changes were not due to a difference in growth rates.


Hyunmin Koo, Joseph A. Hakim, David K. Crossman, Ranjit Kumar, Elliot J. Lefkowitz, Casey D. Morrow. Individualized recovery of gut microbial strains post antibiotics. npj Biofilms and Microbiomes, 2019; 5 (1) DOI: 10.1038/s41522-019-0103-8

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 29 November 2019

Single mutation changes function of bacteria's transporter proteins

Swapping a single amino acid in a simple bacterial protein changes its structure and function, revealing the effects of complex gene evolution, finds a new study published in the journal eLife. The study -- conducted using E. coli bacteria -- can help researchers to better understand the evolution of transporter proteins and their role in drug resistance.

Cells are bound by a thin membrane layer that protects its interior from the outside environment. Within this layer are transporter proteins that control which substances are allowed in and out of the cell. These transporters actively move substances across the cell membrane by loading cargo on one side of the layer, then changing their structure to release it on the other side.

Membrane transporters are typically made up of multiple repeating units. In more complex transporters, the genetic sequence for each of these structural units is fused together into a single gene that codes for the protein.

It is thought that the repeated pattern evolved from smaller membrane protein genes that had duplicated and fused together. But are there evolutionary advantages to having more complex transporters being produced from a single, fused gene?

To investigate this, researchers examined a simple transporter found in E. coli bacteria, which is plentiful in human and animal intestines. However, some strains of E. coli can cause serious illness and are increasingly resistant to antibiotics, which occurs when they pump out toxic compounds using transporters in their membrane. The E. coli transporter, called EmrE, contains two identical protein subunits that work together to move toxic molecules across the membrane and eliminate them from the cell.

Experiments revealed that changing a single amino acid -- the building blocks that make up proteins -- in one of the two protein subunits to make them slightly different from each other dramatically modified the transporter's structure and function. The subtle amino acid swap disrupted the balance of inward- and outward-facing proteins.

Importantly, changing the single amino acid altered the transporter's ability to remove toxic chemicals from E. coli and reduced the bacteria's resistance to drugs -- which may have future implications for drug development and combating antibiotic resistance.

The researchers note that the effects of a minor change to one of the identical halves of the EmrE transporter demonstrates how sensitive membrane transporters are to mutations.


Maureen Leninger, Ampon Sae Her, Nathaniel J Traaseth. Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations. eLife, 2019; 8 DOI: 10.7554/eLife.48909

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 28 November 2019

Mode of delivery at birth may play key role in shaping the child's skin microbiome

The maturation of skin microbial communities during childhood is important for the skin health of children and development of the immune system into adulthood, but only a few studies have analyzed the microbiota in young children. In a new study, investigators in China found that bacterial genera in children were more similar to those of their own mothers than to those of unrelated women. Their data suggest that the mode of delivery at birth could be an important factor in shaping the child's microbiome.

"To date, research into the maternal influence on her child's skin microbiome has been mostly limited to a narrow postpartum window in children younger than one year old and fewer studies have explored the maternal relationship with the child's microflora after infancy," explained lead investigator Zhe-Xue Quan, Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Institute of Biodiversity Science, School of Life Sciences, Fudan University, Shanghai, China. "Therefore, we expanded the scope of our analysis to include sampling from different body sites and direct comparison to the mother of the child in order to provide novel insights."

Investigators examined the changes in the skin microbiota and analyzed relationships between the skin microbiome and microenvironment as well as between the microbiota composition of children and mothers in 158 children between one and ten years old. The mothers of 50 of these children were randomly selected and recruited to represent different child age groups. Microbiota structures between the children and their mothers were compared using 16S rRNA gene amplicon sequencing. Samples were taken from three skin sites: center of the cheek; one quarter of the length of the forearm from the hand; and the center of the calf. Data for 474 samples (three skin sites per child) were pooled into 36 groups according to age, gender, and skin site.

Sample location and age were the primary factors determining a child's skin bacterial composition, which differed significantly among the three sites. However, there was negative correlation between the abundances of Streptococcus and Granulicatella and age. The relative abundances of most bacterial genera in children were more similar to those of their own mothers than those of unrelated women. The facial bacterial composition of 10-year-old children was strongly associated with whether they were born by Caesarian section or vaginal delivery.


Ting Zhu, Xing Liu, Fan-Qi Kong, Yuan-Yuan Duan, Alyson L. Yee, Madeline Kim, Carlos Galzote, Jack A. Gilbert, Zhe-Xue Quan. Age and Mothers: Potent Influences of Children’s Skin Microbiota. Journal of Investigative Dermatology, 2019; DOI: 10.1016/j.jid.2019.05.018

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 27 November 2019

Skin UV exposure reflected in poop

The Sun can indeed shine out of your backside, suggests research. Not because you’re self-absorbed, but because you’ve absorbed gut-altering UV radiation.

This is the first study to show that skin exposure to UVB light alters the gut microbiome in humans. Published in Frontiers in Microbiology, the analysis suggests that vitamin D mediates the change – which could help explain the protective effect of UVB light in inflammatory diseases like MS and IBD.

Ratifying rodent studies

Sun exposure, vitamin D levels and the mix of bacteria in our gut are each associated with risk of inflammatory conditions like MS and IBD. Scientists hypothesize that a causal chain links the three.

Exposure to UVB in sunlight is well-known to drive vitamin D production in the skin, and recent studies suggest that vitamin D alters the human gut microbiome. However, that UVB therefore causes gut microbiome changes, via vitamin D production, has so far been shown only in rodents.

In a new clinical pilot study, researchers tested the effect of skin UVB exposure on the human gut microbiome.

Healthy female volunteers (n=21) were given three one-minute sessions of full-body UVB exposure in a single week. Before and after treatment, stool samples were taken for analysis of gut bacteria – as well blood samples for vitamin D levels.

Rich as feces

Skin UVB exposure significantly increased gut microbial diversity, but only in subjects who were not taking vitamin D supplements during the (winter) study (n=12).

“Prior to UVB exposure, these women had a less diverse and balanced gut microbiome than those taking regular vitamin D supplements,” reports Prof. Bruce Vallance, who led the University of British Columbia study. “UVB exposure boosted the richness and evenness of their microbiome to levels indistinguishable from the supplemented group, whose microbiome was not significantly changed.”

The largest effect was an increase in the relative abundance of Lachnospiraceae bacteria after the UVB light exposures.

“Previous studies have linked Lachnospiraceae abundance to host vitamin D status,” adds Vallance. “We too found a correlation with blood vitamin D levels, which increased following UVB exposure.”

This indicates that vitamin D at least partly mediates UVB-induced gut microbiome changes.

The results also showed some agreement with mouse studies using UVB, such as an increase in Firmicutes and decrease in Bacteroidetes in the gut following exposure.

Getting to the bottom of UVB’s protective effect

“In this study we show exciting new data that UVB light is able to modulate the composition of the gut microbiome in humans, putatively through the synthesis of vitamin D,” Vallance sums up.

The study is not designed to show the exact mechanism by which the microbiome changes occur, but both UVB and vitamin D are known to influence the immune system.

“It is likely that exposure to UVB light somehow alters the immune system in the skin initially, then more systemically, which in turn affects how favorable the intestinal environment is for the different bacteria,” suggests Vallance.

“The results of this study have implications for people who are undergoing UVB phototherapy and identifies a novel skin-gut axis that may contribute to the protective role of UVB light exposure in chronic inflammatory diseases like MS and IBD.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 26 November 2019

A new approach to tackle superbugs

Scientists have uncovered a novel antibiotic-free approach that could help prevent and treat one of the most widespread bacterial pathogens, using nanocapsules made of natural ingredients.

Helicobacter pylori (H. pylori) is a bacterial pathogen carried by 4.4 billion people worldwide, with the highest prevalence in Africa, Latin America and the Caribbean.
Although the majority of infections show no symptoms, if left untreated the pathogen can cause chronic inflammation of the stomach lining, ulcers and is associated with an increased risk of gastric cancer.

In 2017, the World Health Organisation included H. pylori on its list of antibiotic-resistant "priority pathogens" -- a catalog of bacteria that pose the greatest threat to human health and that urgently need new treatments.

Current treatments involve multi-target therapy with a combination of antibiotics, but this has promoted the emergence of resistant strains.

Now, UK and German scientists have uncovered a novel antibiotic-free approach using only food- and pharmaceutical-grade ingredients, which are non-toxic and safe for consumption, to be used as a supplement to complement antibiotic current therapies.

The formulation is delivered through billions of bundled together nanocapsules, which are smaller than a human blood cell, and prevents the bacteria from attaching to and infecting the stomach cells.

The team, which includes researchers from the universities of Leeds, Münster and Erlangen, hope the nanocapsules could be used as a preventative measure, as well as helping eradicate H. pylori and reduce antibiotic resistant strains.


Bianca Menchicchi, Eleni Savvaidou, Christian Thöle, Andreas Hensel, Francisco M. Goycoolea. Low-Molecular-Weight Dextran Sulfate Nanocapsules Inhibit the Adhesion of Helicobacter pylori to Gastric Cells. ACS Applied Bio Materials, 2019; DOI: 10.1021/acsabm.9b00523

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 25 November 2019

Blockchain innovations for pharmaceuticals and healthcare

A blockchain is a time-stamped series of immutable record of data that is managed by a cluster of computers not owned by any single entity (this means it is ‘decentralized’). Each of these blocks of data (a ‘block’) are secured and bound to each other using cryptographic principles (the ‘chain’). This makes the blockchain an incorruptible digital ledger of transactions that can be programmed to record anything of value, such as time, temperature, vibration, costs and so on.

Blockchain in the full-blown sense has yet to be accepted by pharmaceutical  regulators; however, the U.S. FDA agreed in 20198 to a pilot study. This blog posts looks at what blockchain is and how it might work in the context of pharmaceuticals and healthcare. This post also looks at areas where blockchain can be directed and what advantages it can deliver to pharma. Of these different applications, avoiding the falsification of medicines is probably the most important.

Tim Sandle has written a new article for the IVT Network.

While blockchain as yet to take-off fully in the pharma world, across other industries (such as food and shipping) it is regarded as one of the most disruptive technologies within the digital transformation paradigm, introducing greater security and transparency to economic transactions. As soon as it become accepted by pharmaceutical regulators, it will change the industry permanently - passing information from A to B in a fully automated and safe manner.

Sandle, T. (2019) Blockchain innovations for pharmaceuticals and healthcare, IVT Network, at:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 24 November 2019

New species of choanoflagellate discovered

Scientists have found a new species of choanoflagellate. This close relative of animals forms sheets of cells that 'flip' inside-out in response to light, alternating between a cup-shaped feeding form and a ball-like swimming form. The organism could offer clues about animals' early evolution.

Choanoflagellates inhabit the no-man's-land of protozoans -- creatures that are clearly not bacteria, but also don't qualify as complex multicellular life, like plants or animals. Each choanoflagellate cell has a tail-like flagellum surrounded by a ring of tiny hairlike structures, like a sperm cell wearing a fluffy Elizabethan collar.

When C. flexa's sheets curl up into a ball with the flagella pointing outward, the ball swims quickly by waving the tail-like structures. Or the sheet can flip into a cup shape by unfolding and then curling in the opposite direction, in such a way that all the flagella face inside.

A series of experiments revealed that the organism reacts to light using a light-sensing protein and other molecules, some of which C. flexa must obtain from the bacteria they eat. What's more, King's team figured out the precise mechanism for the flip: the cells simultaneously flare their collars into a cone shape, bending the sheet of cells and causing a contraction similar to that of an animal's muscle. This inspired the team to look at other choanoflagellates, some of which turned out to have the same ability. The finding suggests this particular contracting mechanism likely pre-dates the first animals.


Thibaut Brunet, Ben T. Larson, Tess A. Linden et al. Light-regulated collective contractility in a multicellular choanoflagellate. Science, 2019 DOI: 10.1126/science.aay2346

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 23 November 2019

WHO Proposal to discontinue the test for undue toxicity (chapter 3.7) in the international pharmacopoeia

A draft document has been issued to a limited audience following the decision of the WHO Expert Committee on Biological Standardization (ECBS), it is proposed to omit chapter 3.7, “Undue Toxicity” in The International Pharmacopoeia and its reference in the monographs on Kanamycin acid sulfate and Kanamycin monosulfate.

The test is sometimes called the abnormal toxicity test.

The principle of the test consists of injecting the product under investigation into guinea pigs and/or mice.  The sample passes the test if no animal shows any signs of illness, relevant body weight changes or dies within a certain period.  The exact test design and name varies between the different pharmacopoeias and requirements.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 22 November 2019

Implementation of the new Veterinary Medicines Regulation

The new Veterinary Medicines Regulation (Regulation (EU) 2019/6) will modernise the existing rules on the authorisation and use of veterinary medicines in the European Union (EU) when it becomes applicable on 28 January 2022. It contains new measures for increasing the availability and safety of veterinary medicines and enhances EU action against antimicrobial resistance. The European Medicines Agency (EMA) is working closely with the European Commission and other EU partners in preparation for the implementation of the new Regulation.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 21 November 2019

IEC 31010:2019 Risk management — Risk assessment techniques

A new ISO standard has been issued, on the subject of risk assessment methods.

IEC 31010, Risk management — Risk assessment techniques, features a range of techniques to identify and understand risk. It has been updated to expand its range of applications and to add more detail than ever before. It complements ISO 31000, Risk management.

IEC 31010 describes the process to be followed when assessing risk, from defining the scope to delivering a report. It introduces a wide range of techniques for identifying and understanding risk in a business or technical context.

For details see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 20 November 2019

Modulation of the microbiome

A Nature Review has been issued, covering the gut microbiota’s role in colorectal cancer.

According to new experimental evidence from Jun Yu’s group at The University of Hong Kong, the gut microbiota is a key cog in the formation and progression of colorectal cancer. Gut bacteria play a role in preventing adverse effects of treatment too. Clinical data demonstrated that clear changes in the number of specific bacteria are detected in patients and can even serve as a biomarker for disease screening to help to inform a patient’s response to a certain treatment. It’s clear that modulation of the gut microbiota is an excellent strategy to enhance treatment efficacy and reduce adverse effects of colorectal cancer therapies.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 19 November 2019

What Technologies Will Have the Biggest Impact on Pharma?

Medical science has come a long way since the days of leeches and trepanning, but new technologies are emerging every day that will change the way we look at pharmaceutical science. Here are the ones that will have the most significant impact on pharma, once the industry learns to adopt them.

A guest post by Megan Ray Nichols

Machine Learning and Analytics

Machine learning, or programming computers to learn and grow from the information they're given, is a stepping stone between the digital networks we use today and true artificial intelligence. This technology may still be in its infancy, but its applications in the industry are growing by the day. One potential use in the pharmaceutical industry is in drug discovery and manufacturing.

Drug discovery is typically slow and expensive. Pharmaceutical researchers start by selecting a target and analyzing millions of compounds before they might discover one that proves to be a viable potential treatment. Half a dozen steps later, it might make it to clinical trials, and then after a decade of additional testing, it could be made available to consumers.

Machine learning programs can consolidate many of these steps, from target selection through pre-clinical stages. While it will never replace the need for clinical trials, it could reduce time and money spent on drug discovery while still producing new viable medications. According to industry experts, these applications could save the health care sector $150 billion a year by 2026.

IoT and Networked Sensors

The Internet of Things (IoT) is showing up in nearly every industry. If you've got any smart devices in your home, from an Amazon Echo to a smart garage door opener, you're already part of it. This technology could become an invaluable part of the pharmaceutical industry once adopted by existing companies.

These sensors are capable of sending and receiving information, can be networked to a central hub, and may be programmed to do nearly anything. In the pharmaceutical sector, IoT sensors are becoming popular for real-time equipment monitoring, environmental monitoring and control in manufacturing plants. They also watch the supply chain once medications leave the factory en route to pharmacies and hospitals around the country.

IoT requires additional equipment and IT professionals to install it and keep it running. Once adopted, it could address many of the problems — such as a lack of transparency — that the pharmaceutical industry is currently facing.

Automation and Robotics

Automation isn't a new concept in manufacturing, but many pharmaceutical companies are starting to turn to autonomous practices to create medications and medical technology. It's already used in the filling, packing and inspection in more than one-third of pharmaceutical factories.

More recently, companies have started incorporating a process known as Raman Spectroscopy to analyze drugs before they're shipped. Ramen spectroscopy uses single-frequency lasers to examine the vibrational frequency of the molecular bonds in the medications. The drugs are tested by the computer to determine whether they're safe to ship.

Automation is also making an appearance in lab settings. The ACAPELLA-1K is a DNA prep system that uses automation and highly specialized fluid processing systems to prepare 1,000 samples of DNA for sequencing in less than eight hours. The ACAPELLA system can aspirate, dispense, mix, transport, and heat or cool the fluids as necessary to get them ready for sequencing, all with the press of a button. 

3D Printing

3D printing started as a toy for hobbyists and CAD designers to turn their designs into reality, but it's started to make an appearance in nearly every industry. There's even a 3D printer on the International Space Station. Millions of people use pills and capsules every single day — and many of them are difficult to swallow or taste terrible. 3D printing might be the solution to these problems. Instead of using the same size and shape of a pill for everyone, 3D printing would enable pharmaceutical companies to customize their medications for the needs of each patient.

The first 3D printed drug to receive FDA approval was Spritam, a medication from Aprecia Pharmaceuticals used to treat epilepsy in 2016. It created new technology to build each pill, one layer at a time, to make a dissolvable pill that's easier to swallow. While 3D printing isn't more efficient than traditional pill-making methods, it can help make taking your medicine easier and less uncomfortable. 

Looking Forward

Medical technology is changing the way we do everything from how we manufacture pills to how we discover new drugs and treatments. These technological advances will alter the very foundation of the pharmaceutical industry, once current pharma companies adopt them. It might not be too long before you take a pill that was discovered and designed by a machine learning program and created by a 3D printer before being delivered to your door.

Pharmaceutical Microbiology Resources (

Monday, 18 November 2019

Cleanroom regulatory trends: A review of FDA warning letters

Cleanrooms remain a central focus of regulatory inspections and it is good practice for those working within pharmaceuticals and healthcare to assess regulatory trends. This task is difficult within Europe, where only broad overviews are released (due to data privacy restrictions) and it becomes complex when assessing output from U.S. FDA, given the hundreds of warning letters issued. To assist with this process, this article assesses recent FDA warning letters and draws out the main trends and significant non-compliances relating to cleanroom design, testing and operations.

Tim Sandle has written a new article:

Sandle, T. (2019) Cleanroom regulatory trends: A review of FDA warning letters, Clean Air and Containment Review, Issue 38, pp20-24

For details, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 17 November 2019

Supplier Oversight and Quality Control for Patient Safety

Tim Sandle has taken part in a podcast with the Institute of Validation Technology as part of their ‘Voices In Validation’ series.

Stacey Bruzzese talks to Dr. Tim Sandle, the Head of Microbiology and Sterility Assurance at Bio Products Laboratory Limited.

Stacey and Tim cover a variety of topics:

  • For pharma manufactures, how does fewer employees, smaller inventory, less space and reduced time impact patient safety?
  • What type of supplier oversite is necessary?
  • As supply chains become more and more digital, how does IoT impact processes and programs controlling quality?
  • How do Big Data and Cloud Computing relate to patient safety, accessibility and affordability?
  • What does Dr Sandle see as the next major shift in supply chain migration?

To access the podcast, see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 16 November 2019

New fluorescence method reveals signatures of individual microbes

When viewed with specialized microscopes, microbial cells show an individual fluorescence pattern, or signature, that depends on the mixture of biomolecules contained within the cells. That complex mixture, with its telltale signature, in turn depends on the type of microbe and its physiological state, such as whether it is growing or what it is consuming as a food source.
University of Tsukuba researchers have developed a new method, named CRIF (Confocal Reflection microscopy-assisted single-cell Innate Fluorescence), to detect the fluorescence signatures of individual microbial cells. The method is non-destructive, meaning the cells remain alive, and allows cells to be studied in realistic three-dimensional environments. Importantly, the new method can be used to view individual cells within mixtures of different types of microbe, unlike many standard techniques that work best with "pure" populations where the cells are all alike. The team recently published their findings in Applied and Environmental Microbiology.

"We used a confocal microscope, which can generate images from three-dimensional materials -- rather like comparing a sequence of slices to build up an image of a whole intact structure. This enabled us to find the locations of the microbial cells within the sample," says lead and co-corresponding author Yutaka Yawata. "Combining this with spectroscopy to measure a set of fluorescence signals under the microscope, we were able to see the different types of microbes within the sample, and read their signatures to identify the individual cells."

The team went on to train computer models to read the fluorescence signatures and distinguish different types of cells. The models learned to recognize cells automatically, even when looking at different cells with very similar shapes and sizes, and analyze the images for cell signatures to identify the cells according to their type and physiological state.
"Our technique to recognize and track the innate fluorescence signatures of each of the individual cells within three-dimensional samples opens up exciting new opportunities to explore mixed microbial populations, as found in natural environments," says co-corresponding author Nobuhiko Nomura. "It will help researchers understand how microbes grow and interact with each other in the real world."


Yutaka Yawata, Tatsunori Kiyokawa, Yuhki Kawamura, Tomohiro Hirayama, Kyosuke Takabe, Nobuhiko Nomura. Intra- and Interspecies Variability of Single-Cell Innate Fluorescence Signature of Microbial Cell. Applied and Environmental Microbiology, 2019; 85 (18) DOI: 10.1128/AEM.00608-19

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 15 November 2019

Antibiotic resistant genes prevalent in groundwater

With climate change comes increasing water shortages, and potentially longer periods of drought. As policymakers look urgently to wastewater recycling to stem the gap in water resources, the question is -- how best to reuse water and ensure public safety. New and emerging contaminants like antibiotic resistant genes (ARGs) pose a potential hazard to public safety and water security. One concern is the spread of ARGs through the water system and an increase in development of antibiotic-resistant super bugs.

Researchers from the University of Southern California studied and compared samples from an advanced groundwater treatment facility in Southern California and groundwater aquifers to detect differences in ARG concentrations. While they found that the advanced groundwater treatment facility reduced nearly all targeted ARGs to below detection limits, groundwater samples had a ubiquitous presence of ARGs in both control locations and locations recharged with water from the advanced water treatment facility.
Historically, indirect reuse treatment methods in which an environmental barrier is an intermediary step in the water cleaning process have been more popular than the direct "toilet to tap" process. While indirect methods of water reuse treatment were, from a public perception and appetite, considered more reliable, it is actually direct reuse "toilet to tap" approaches which do not introduce an environmental buffer that produce safer, more pure water for potability. The reason for this lies in the way ARGs in the environment can contaminate potable reuse water.

While some ARGs are naturally occurring in microbial communities, antibiotics, ARGs and antibiotic resistant pathogens are on the rise in water sources as a result of the overuse of antibiotics in general. In a typical water treatment cycle, wastewater is treated first at a wastewater treatment facility. The study found that this water remains high in ARGs, as they persist throughout the treatment process. From here, water intended for potable reuse is further purified using advanced physical and chemical techniques including reverse osmosis -- a process that uses a partially permeable membrane to purify drinking water.

Since wastewater treatment plants are not generally designed for removal of micropollutants like antibiotics, they tend to persist in treatment systems, leading to high densities of ARG resistant bacteria at different stages of treatment. When this water is introduced into an aquifer, where ARGs are already naturally occurring, it can become contaminated with ARGs and antibiotic resistant bacteria. To further complicate the issue, ARGs are easily transferred through horizontal gene transfer, increasing the risk for antibiotic resistant pathogens.


Moustapha Harb, Phillip Wang, Ali Zarei-Baygi, Megan H. Plumlee, Adam L. Smith. Background Antibiotic Resistance and Microbial Communities Dominate Effects of Advanced Purified Water Recharge to an Urban Aquifer. Environmental Science & Technology Letters, 2019; DOI: 10.1021/acs.estlett.9b00521

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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