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Bacteria of the species Pseudomonas aeruginosa are antibiotic-resistant hospital germs that can enter blood, lungs and other tissues through wounds and cause life-threatening infections. In a joint project, researchers from the Universities of Freiburg and Strasbourg in France have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections. At the same time, it could be a target for future treatments. The results were recently appeared in the journal EMBO Reports.
Many bacterial species use sugar-binding molecules called lectins to attach to and invade host cells. Lectins can also influence the immune response to bacterial infections. However, these functions have hardly been researched so far. A research consortium led by Prof. Dr. Winfried Römer from the Cluster of Excellence CIBSS — Centre for Integrative Biological Signalling Studies at the University of Freiburg and Prof. Dr. Christopher G. Mueller from the IBMC — Institute of Molecular and Cell Biology at the CNRS/University of Strasbourg has investigated the effect of the lectin LecB from P. aeruginosa on the immune system. It found that isolated LecB can render immune cells ineffective: The cells are then no longer able to migrate through the body and trigger an immune response. The administration of a substance directed against LecB prevented this effect and led to the immune cells being able to move unhindered again.
LecB barricades the path for immune cells
As soon as they perceive an infection, cells of the innate immune system migrate to a nearby lymph node, where they activate T and B cells and trigger a targeted immune response. LecB, according to the current study, prevents this migration. “We assume that LecB not only acts on the immune cells themselves in this process, but also has an unexpected effect on the cells lining the inside of the blood and lymph vessels,” Römer explains. “When LecB binds to these cells, it triggers extensive changes in them.” Indeed, the researchers observed that important structural molecules were relocated to the interior of the cells and degraded. At the same time, the cell skeleton became more rigid. “The cell layer thus becomes an impenetrable barrier for the immune cells,” Römer said.
An effective agent against LecB
Can this effect be prevented? To find out, the researchers tested a specific LecB inhibitor that resembles the sugar building blocks to which LecB otherwise binds. “The inhibitor prevented the changes in the cells, and T-cell activation was possible again,” Mueller said, summarizing the promising results of the current study. The inhibitor was developed by Prof. Dr. Alexander Titz, who conducts research at the Helmholtz Institute for Pharmaceutical Research Saarland and Saarland University.
Further studies are needed to determine how clinically relevant the inhibition of the immune system by LecB is to the spread of P. aeruginosa infection and whether the LecB inhibitor has potential for therapeutic application. “The current results provide further evidence that lectins are a useful target for the development of new therapies, especially for antibiotic-resistant pathogens such as P. aeruginosa,” the authors conclude.

Decisions on cancer treatment could become better tailored to individual patients with the adoption of a new imaging method being developed by University of Michigan researchers that maps the chemical makeup of a patient’s tumor.
Today, treatment methods for cancer — whether surgery, radiation therapy or immunotherapy — are recommended based mainly on the tumor’s location, size and aggressiveness. This information is usually obtained by anatomical imaging — MRI or CT scans or ultrasound and by biological assays performed in tissues obtained by tumor biopsies.
Yet, the chemical environment of a tumor has a significant effect on how effective a particular treatment may be. For example, a low oxygen level in the tumor tissue impairs the effectiveness of radiation therapy.
Now, a team of scientists from the University of Michigan and two universities in Italy has demonstrated that an imaging system that uses special nanoparticles can provide a real-time, high-resolution chemical map that shows the distribution of chemicals of interest in a tumor.
It could lead to a way to help clinicians make better recommendations on cancer therapy tailored to a particular patient — precision medicine.
Their research, published in ACS Nano, reports on the first demonstration of an in vivo chemical imaging method generalizable to any chemical of interest, according to U-M chemistry professor Raoul Kopelman, one of the senior authors on the paper.

The researchers used a method for “chemical imaging” of tissues called photo-acoustic chemical imaging, or PACI.
“The novelty of this method is that it is performed in vivo, directly inside the body,” Kopelman said.
The team tested their system in mice that were implanted with tissue from a biopsy of a patient’s tumor, called a xenograft. Patient-derived xenografts recapitulate the genetic and biological characteristics of the patient’s tumor.
PACI employs nanoparticles that have been developed in the past decades, by Kopelman and others, that can be injected into the mouse to target the tumor and sense a particular chemical of biomedical interest, such as oxygen, sodium or potassium.
When this nanosensor is activated by infrared laser light that is able to penetrate into the tumor tissues, an ultrasound signal is generated that can be used to map the concentration and distribution of that particular chemical.

The PACI method could be used in a mouse xenograft to repeatedly follow the characteristics of a particular patient’s tumor to evaluate the chemical environment of the tumor over time.
“This would allow for optimization of treatment methods for a particular patient — precision medicine,” Kopelman said.
Kopelman and colleagues employed the PACI with a nanoparticle targeted to sense oxygen. Following radiation therapy of the tumor in the mouse, the researchers found a significant correlation between oxygen levels in each part of the tumor and how well radiation therapy destroyed tumor tissue — the lower the local oxygen in the tissue, the lower the local radiation therapy efficacy.
“We thus provide a simple, noninvasive, and inexpensive method to both predict the efficacy of radiation therapy for a given tumor and identify treatment-resistant regions within the tumor’s microenvironment,” Kopelman said.
“Such chemical mapping would help the clinical team prescribe a personalized, optimal treatment for a given patient’s tumor, based on the new diagnostics from the tumor xenograft’s chemical mapping.”
In this research, PACI has been employed in patient-derived xenografts. The ultimate goal would be the ability to make the chemical maps in patients directly.
That would be feasible, says Kopelman, with fiber optics that could be threaded through the patient’s venous system, as is done in cardiac procedures, to get near the tumor. The nanosensor could then be activated by the laser, but it requires nanosensors developed for each chemical of interest, and each nanosensor would need to be approved by the Food and Drug Administration.
In addition to Kopelman, U-M researchers include Janggun Jo, Jeffrey Folz, Celina Kleer, Xueding Wang, Maria Gonzalez, Ahmad Eido, Shilpa Tekula and Roberta Caruso.
Italian collaborators are Sebastiano Andò of the University of Calabria and Alessandro Paolì of the University of Calabria and University of Padua. The work was supported by National Institutes of Health grants to Kopelman, Wang and Kleer.

Two Conservative MPs clashed in a debate on whether the menopause was a disability and both accused the other of talking over them.Minister for Women and Equalities Kemi Badenoch said people should use “all legal avenues open to them” and told the women and equalities committee chairman “not to put words in my mouth”.Caroline Nokes said her fellow Conservative was not answering the question, and that she was quoting Mrs Badenoch’s words back at her.

A new Australian study focused on defence veterans’ mental health has found strong evidence that assistance dogs used in conjunction with traditional therapies provide the most effective treatment outcomes.
Almost 90 per cent of veterans reported improvements in their post-traumatic stress, depression and anxiety 12 months after being matched to an assistance dog, according to researchers from the University of South Australia (UniSA), University of Adelaide, and Military and Emergency Services Health Australia (MESHA).
Of the 16 returned veterans who took part in the study, 63 per cent reported “significant clinical improvements” to their mental health thanks to an assistance dog provided by the Operation K9 Program run by See Differently with the Royal Society for the Blind.
The study, funded by The Hospital Research Foundation Group, is the first in Australia to use self-reported measures, clinical assessments, and face-to-face interviews with veterans to investigate the value of an assistance dog over time.
It is published in the International Journal of Environmental Research and Public Health.
UniSA Master of Clinical Psychology student Melissa Sherman, who analysed the data, says the findings are relevant to policymakers and demonstrate the power of human-animal relationships.

“Previous studies have shown that existing treatments for post-traumatic stress among returned veterans are not ideal, with high dropout rates and poor adherence,” Sherman says.
“This study provides clear evidence that assistance dogs can play a key role in a veteran’s recovery from post-traumatic stress and other mental health conditions, supporting existing treatments.”
Of the 5000 ADF members who transition from the forces to civilian life every year, 46 per cent experience mental health issues, including suicidal thoughts, anxiety, and depression. Almost a quarter of them are diagnosed with post-traumatic stress in their lifetime.
“This is an important issue that needs addressing,” according to MESHA Executive Director Miranda Van Hooff, an Adjunct Associate Professor at both UniSA and the University of Adelaide.
Three major themes emerged from the study: that assistance dogs were a “life changer,” a constant companion, and helped returned veterans to increase their social interactions.

“For many veterans, an assistance dog gave them a sense of purpose and a reason to live,” Assoc Prof Van Hooff says.
Veterans reported their dog helped them “reclaim their life,” giving them independence and a way to manage their mental health issues and fluctuating emotions, including hypervigilance.
Some participants described their dog as “a comfort or security blanket,” with one veteran saying he was a recluse for many years until being matched with an assistance dog: ‘Now, every day is an adventure, giving me something to look forward to’.
The study showed a slight drop in participants still reporting suicidal feelings after 12 months, but the reduction was not significant. The main benefits were a large reduction in depression, anxiety, and post-traumatic stress symptoms.
Researchers say the study was limited by the lack of a control group of veterans with post-traumatic stress not receiving an assistance dog, and the small number of study participants due to the cost of breeding, training, and matching dogs to veterans.
Further research is being conducted by the team to overcome these limitations.